Search results for “mechanism

About 100 results in articles

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100 articles

Lineage-Specific Disruption of Hematopoiesis by Oxaliplatin: Mechanisms of Erythropoietin Resistance and Immune Suppression

Feb 2026 DOI 10.14302/issn.2372-6601.jhor-25-5944
Y. Berezin MikhailCorresponding author

Background Oxaliplatin, a widely used chemotherapeutic agent, is associated with hematologic toxicities such as anemia, leukopenia, and thrombocytopenia. Despite their clinical relevance, the molecular mechanisms underlying lineage-specific bone marrow suppression remain poorly understood. Methods We administered oxaliplatin to mice over eight weeks and performed RNA-sequencing (RNA integrity >8) on bone marrow alongside peripheral blood analysis and cytokine profiling. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. For that, we applied a thematic Gene Ontology (thematicGO) enrichment method that groups GO terms into biologically meaningful categories, such as hematopoietic lineage disruption, cell cycle arrest, and cytokine signaling. Results Oxaliplatin induced broad transcriptional suppression of erythropoiesis and lymphopoiesis, with 3,691 DEGs identified (FDR<0.05, |FC|>1.5). Upregulation of Cdkn1a and downregulation of E2f2 suggest G1/S cell cycle arrest, correlating with repression of key erythroid maturation genes (e.g., Spta1, Slc4a1, Alas2) and hemoglobin subunits (Hba-a1/2, Hbb-bs/t). Despite a ~3000-fold increase in renal Epo expression, bone marrow Epor was reduced, indicating erythropoietin resistance. B and T cell markers were also significantly downregulated, signifying a collapse in adaptive immunity. Notably, neutrophil populations were largely spared. Cytokine analysis in plasma revealed a pro-inflammatory shift with elevated TNF-α and reduced TGF-β, potentially exacerbating hematopoietic dysfunction. Conclusions Oxaliplatin induces a lineage-dependent suppression of hematopoiesis, driven by coordinated cell cycle arrest, metabolic stress, and disrupted cytokine signaling. RNA-seq analysis enabled integration of transcriptomic findings into coherent biological themes. These findings provide mechanistic insights into oxaliplatin’s hematologic toxicity linking bone marrow failure (potentially reversible) via interconnected inflammatory and metabolic pathways and may inform therapeutic strategies to minimize or restore myelosuppression in cancer patients.

Women's Mental Health Open Access

Exploring the Mechanism of Complex Lemon-Angelica Sinensis-Boswellia Essential Oil on Anxiety Disorders with Melasma Through Network Pharmacology and Experimental Validation

Dec 2025
Liu LipingCorresponding author

The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.

Veterinary Healthcare Open Access

Detection of carbapenem resistance mechanisms among Avian Pathogenic Escherichia coli (APEC) isolated from broiler chickens

May 2023 DOI 10.14302/issn.2575-1212.jvhc-23-4521
El- shaer AyaCorresponding author

Background The emergence and spread of carbapenem-resistant gram-negative bacteria pose a serious threat to human health. Currently, little is known about the molecular mechanisms underlying carbapenem -resistance and their prevalence among APEC in Egypt. The aim of this study was to detect APEC in clinically diseased broiler chickens collected from broilers farms located at Dakahalia governorates, asses their virulence –associated genes, detect the antimicrobial susceptibility of recovered isolates and to detect genes encoding carbapenemase resistant. Methods A total of 100 organ tissue samples subjected to conventional culture technique for isolation of E. coli. The confirmed E. coli were subjected to disc diffusion method for detection their susceptibility to antimicrobials. Polymerase chain reaction (PCR) was used for detection of APEC virulence genes (hlyA, iutA, ompT, iss, iroN) and six carbapenem- resistant genes namely, blaIMP, blaVIM, blaKPC, blaOXA-48 blaGES and blaNDM,. Results Forty isolates were confirmed to be E. coli  among them, three or more APEC virulence- genes were detected from all isolates. The hlyA gene was detected in 90% (36/40), iroN in 95% (38/40), ompT in 97.5% (39/40), iutA in 92.5% (35/40) and iss was detected in 95% (38/40) of APEC isolates The tested isolates exhibited a remarkable resistance to ampicillin (97.5%), cefuroxime (92.5%), clindamycin (90%), chloramphenicol (62.5%), doxycycline (45%), amikacin (25%) and ciprofloxacin (12.5%). While, the retrieved isolates displayed 100 % sensitivity against imipenem, meropenem, ertapenem, ceftazidime and colistin. Concerning carbapenemase-encoding genes, blaIMP, blaVIM, blaKPC, blaOXA-48, blaGES  couldn’t be detected among the E. coli isolates, while, blaNDM was confirmed in three isolates . Conclusion The detection of NDM as one of the carbapenem resistant genes reveals that the resistant strains are not only capable of infecting humans, but that carbapenams- resistant E. coli (CREC)  has also started to pose a threat to poultry farm and other livestock animals. This may give rise to worries that these food-carrying creatures could infect humans or colonize them.

Respiratory Diseases Open Access

Two-Phase Lung Damage Mechanisms For COVID-19 Disease, and Driving Force and Selectivity in Leukecyte Recruitment and Migration

Mar 2022 DOI 10.14302/issn.2642-9241.jrd-22-4132
Wu JianqingCorresponding author Healthier World (Independent researcher for cause), P. O. Box 689, Beltsville, MD 20704. USA

To understand lung damages caused by COVID-19, we deduced two phases lung damage mechanisms. After the lungs are infected with COVID-19, the affected lung tissue swells and surface properties of pulmonary capillaries change, both contributing to an increased flow resistance of the capillaries. The initial damages are mainly fluid leakage in a limited number of involved alveoli. The increased vascular resistance results in retaining more white blood cells (“WBCs”) in pulmonary capillaries. Some of the WBCs may get into interstitial spaces. When more and more WBCs are dynamically retained, the vascular resistance of pulmonary capillaries further rises; and thus the overall vascular resistance of the lungs rises and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When pulmonary capillary pressures around the alveoli are sufficiently high, the elevated pressure causes interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alvoeli and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and occupation of alvoelar spaces by leaked water result in reduced deformable and compressible spaces, and thus causes a further rise of the vascular resistance of the lungs. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. Among potential influencing factors, the available space in the thorax cage, temperature, and humid are expected to have great impacts. The free space in the thorax cage, lung usable capacity, and other organ usable capacities are the major factors that determine the arrival time of last- phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain how leukecytes are “recruited and migrated” into inflamed tissues by dynamic retention.

Some Regulation Mechanisms of Candidate Genes for Human Cardiovascular Diseases

Mar 2021 DOI 10.14302/issn.2329-9487.jhc-21-3742
Sisay TesfayeCorresponding author Associate Professor

Cardiovascular disease is actually a major cause of mortality, illness and hospitalization worldwide. Several risk factors have been identified that are strongly associated with the development of cardiovascular disease. Public prevention strategies have relied predominately on managing environmental factors that contribute to cardiovascular disease, such as obesity, smoking and lack of exercise. The understanding of the role of genetics in cardiovascular disease development has become much more important to link genetics with the onset of disease and response to therapy. This seeks to examine how genes can predispose individuals to cardiovascular disease and how this knowledge might be applied to more comprehensive preventive strategies in the future. In addition, the review explores possibilities for genetics in cardiovascular disease treatment, particularly through the use of identified driver genes and gene therapy. To fully understand the biological implications of these associations, there is a need to relate them to the exquisite, multilayered regulation of protein expression and regulatory elements, mutation, microRNAs and epigenetics. Understanding how the information contained in the DNA relates to the operation of these regulatory layers will allow us not only to better predict the development of cardiovascular disease but also to develop more effective therapies.

Human Psychology Open Access

Causes and Self-regulatory Mechanisms of Frustration: A Qualitative Exploration of Rock Climbers

Sep 2020 DOI 10.14302/issn.2644-1101.jhp-20-3524
Zheng YuannanCorresponding author Department of Physical Education, Zhejiang University, Hangzhou, China

In recent years, rock climbing has become increasingly popular around the world. However, due to its challenging and competitive nature, it is common for rock climbers to encounter frustration. It leads to negative emotions, reducing participation, and withdrawal behavior, which requires effective self-regulation. Therefore, the purpose of this study was to explore the causes and self-regulatory mechanisms of frustration in rock climbing. Using qualitative methods, 15 rock climbers were interviewed, and 6 themes were identified by thematic analysis. Task comparison and social comparison are the main causes of frustration in rock climbing. The self-regulatory mechanism of task comparative frustration includes focusing on tasks and habitual reflection. The self-regulatory mechanism of social comparative frustration involves emotion regulation and changing goal orientation. It is suggested that future rock climbers, especially beginners, deal with frustration through the self-regulatory mechanisms that can help them enjoy and pursue rock climbing.

Skeletal Muscle Open Access

The Mechanism of Decline of Senescent Skeletal Muscle Satellite Cell Self-Renewal and Regenerative Proliferation: The Role of Heparan Sulfate-FGF-2--FGFR1-p38αMAPK Axis, Sprouty1, miR-1, miR-133 and miR-29a

Apr 2020 DOI 10.14302/issn.2832-4048.jsm-20-3211
Papaconstantinou JohnCorresponding author The Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston Texas 77555-0643

Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344

Cognitive Mechanism of Emotional Validity Influencing Conflict Control

Mar 2019 DOI 10.14302/issn.2574-612X.ijpr-18-2460
Xue SongCorresponding author School of psychology, Nanjing normal University, Nanjing, 210097, China

Conflict control is the ability to choose relevant information and ignore disturbing information in task processing. Previous studies have found that emotions have a certain influence on conflict control, and the research results of positive emotions and negative emotions affect conflict control are inconsistent. This study attempted to explore the effects of different emotional valorization on conflict control, using images of happy, fearful and sad emotional faces to investigate the effects of different emotional valorization and different emotional types on conflict control. The experiment selected 40 participants and used the variable-face Stroop paradigm. The study found that no matter what emotional task, there is a significant conflict effect. The effects of different valency on conflict control are different. All three emotions have a significant effect on conflict control, and positive emotions play a role in promoting conflict control.

Nephrology Advances Open Access

Action Mechanisms and Therapeutic Targets of Renal Fibrosis

Nov 2018 DOI 10.14302/issn.2574-4488.jna-18-2443
Su WeiCorresponding author Department of Nephrology, Baoji Central Hospital, No. 8 Jiangtan Road, Baoji, Shaanxi 721008, China

Renal fibrosis was a chronic and progressive process affecting kidneys in chronic kidney disease (CKD), regardless of cause. Although no effective targeted therapy yet existed to retard renal fibrosis, a number of important recent advances have highlighted the cellular and molecular mechanisms underlying the renal fibrosis. The advances including TGF-β/Smad pathway, oxidative stress and inflammation, hypoxia and gut microbiota-derived from uremic solutes were highlighted that could provide therapeutic targets. New therapeutic targets and strategies that are particularly promising for development of new treatments for patients with CKD were also highlighted.

Energy Conservation Open Access

Flame Propagation Model and Combustion Phenomena: Observations, Characteristics, Investigations, Technical Indicators, and Mechanisms

Jul 2018 DOI 10.14302/issn.2642-3146.jec-18-2232
Aljerf LoaiCorresponding author Department of Basic Sciences, Faculty of Dental Medicine, Damascus University, Damascus, Syria

Critical conditions are usually obtained for ignition in a self-heating solid system consisting of two components generating heat independently, one component being inexhaustible and the other exhaustible by either simple first order or autocatalytic reaction. Ignition depends upon whether the exhaustible component can cause a temperature rise in excess of the upper stationary, but unstable, value possible for the inexhaustible component reacting alone. The system provides a theoretical model for some commonly occurring examples of self-heating and ignition in porous solids containing oxidisable oils. It is shown that: (a) the ignition criterion of the model, which involves a nonarbitrary critical temperature increase, has a high degree of physical reality; (b) the model is, in principle, capable of predicting ignition from primary kinetic and thermal data; (c) it is likely to be possible often to make a reliable prediction of critical size for self-ignition in a two-component system at ordinary atmospheric temperatures by a simple extrapolation from small-scale ignition data, obtained at higher temperatures, in the same way as for ignition due to a single reaction. Examination of both adiabatic and non-adiabatic flame theories showed that a 'steady state' exists only under the special condition that a heat sink exists at the initial temperature. For the general case of freely propagating, non-adiabatic flames only a quasi-steady state can be achieved.

Endocrine Disrupting Chemicals: Epigenetic Relevance and Mechanisms

May 2018
Alatsathianos IoannisCorresponding author Laboratory of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Genetics alone cannot thoroughly expound the environmental impact on the molecular complexity of the endocrine system. Epigenetic-induced alteration in gene expression has emerged as a way in which environmental compounds may exert endocrine effects. The environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to, on a daily basis. Epigenetic mechanisms, mainly the methylation of DNA and the modification of histones, lead to differentiated activation and deactivation of genome domains creating phenotype plasticity and divergent endocrine function among populations and individuals, as well. The issues examined in the present review are related to environmental epigenetics, and more precisely, the epigenetic-mediated modulation and relevance of endocrine disrupting chemicals, focusing on three broad aspects: 1) persistence of EDs, 2) their major hormonal effects and 3) the potential of compounds previously considered as endocrine disruptors to induce epigenetic effects. Evidence suggests that environmental exposures notably impact expression of endocrine-related genes and, thus, affect clinical endocrine outcomes.

DNA And RNA Research Open Access

Investigations of Molecular Evolutionary Mechanisms in Partially Sequenced Heat Shock Protein70 Homologue-Coding Gene of Olive Leaf Yellowing-Associated Virus Isolates from Tunisia

Feb 2016 DOI 10.14302/issn.2575-7881.jdrr-15-849
BOULILA MoncefCorresponding author Professor, Université de Sfax- Institut de l’Olivier- B.P. 14, 4061 Sousse Ibn Khaldoun, Tunisia.

Reverse Transcription Polymerase Chain Reaction (RT-PCR) using new designed primers pair for Heat Shock Protein70 homologue (HSP70h) of Olive leaf yellowing-associated virus revealed 667 amplified product of 10 olive accessions collected from various olive-growing regions in Tunisia. Amplicons were cloned and sequenced. The sequences were deposited in the international databases. Pairwise sequence comparisons among 10 Tunisian isolates along with a reference sequence (AJ440010) extracted from GenBank revealed a nucleotide identity of 86.06-99.40 and an amino acid similarity of 91.89-99.55. Sequence multiple alignments were searched for evidence of recombination using three methods, ie. Differences of Sums of Squares (DSS) implemented in TOPALi v2.5 software and Single Breakpoint (SBP) along with GARD, a genetic algorithm, both incorporated in HyPhy package. All used methods pointed out the presence of putative breaking points in partially sequenced HSP70h-coding gene. Since failing to account for recombination can mislead the phylogeny inference and can elevate the false positive error rate in positive selection assessment, the use of GARD resulted in the reconstruction of different phylogenies on the left as well as on the right sides of putative recombination breaking points, and the 11 accessions were distributed into at least three clusters compared to MEGA6 software which delineated only two clades. Nonetheless, by dividing the aligned sequences at breakpoints into separate sequence sets, MEGA6 delineated a clustering pattern different from the former two. As a result, recombination reshuffled the affiliation of the different accessions to the clusters. Analysis of selection pressures exerted on HSP70h encoded protein using different models (SLAC, IFEL, FEL, REL, PARRIS, FUBAR, MEME, GA Branch, and PRIME) taking into account recombination, and implemented in HyPhy package, revealed that it underwent predominantly purifying selection as confirmed by Tajima’s D, Fu and Li’s D and F tests, and SNAP algorithm. However, a few sites were also under positive selection as assessed by various models such as FEL, IFEL, REL, MEME, and PRIME.

Mechanisms Associated with Acquisition of Resistance to Butyrate-Induced Apoptosis in Colorectal Cancer Cells Using Gene Expression Analysis

Dec 2014 DOI 10.14302/issn.2326-0793.jpgr-14-598
YC Fung KimCorresponding author CSIRO Preventative Health National Research Flagship, Australia

Colorectal cancer is one of the most commonly diagnosed cancers worldwide and its prevalence can be reduced by changes to lifestyle and diet. Fermentation of dietary fibre by the gut microbiota and formation of short chain fatty acids, in particular butyrate, is widely thought to play a role in preventing development of the disease. Despite butyrate’s known pro-apoptotic effects, a subpopulation of cancer cells is able to overcome these anti-neoplastic effects of colonic luminal butyrate to proliferate and establish tumours in vivo. In this study, a time course analysis of HT29 and HT29-BR cells treated with butyrate was conducted and global gene expression analysis was used to identify novel mechanisms associated with butyrate-induced apoptosis and in the acquisition of butyrate resistance. Bioinformatic analysis of the data identified deregulated O-GlcNAcylation activity and disruption to gene transcription by BRD4 as possible factors involved with butyrate-induced apoptosis. EGF signalling was identified as being potentially involved in the acquisition of butyrate resistance. Furthermore, the expression of the minichromosome maintenance protein family was significantly reduced in the HT29-BR cell line reflecting disruptions to the DNA replication process. Together, this may confer a unique survival advantage for cells with acquired butyrate resistance.

High-Throughput Complex Disease Modeling for Ethical Drug Discovery: Clinical Relevance of a NAM Platform for Cancer Biomarker Development

May 2026 DOI 10.14302/issn.2572-3030.jcgb-26-6307
Faisst Arne-C.Corresponding author

The development of tumor biomarkers derived from blood, or its components, has become pivotal in advancing early cancer diagnosis. Malignant transformations induce cancer-specific alterations in the transcriptome, proteome, and secretome of tumor cells. Recent studies highlighted similar alterations in peripheral blood mononuclear cells (PBMCs) in cancer patients, which appear to mirror the state of transformation in tumor cells. These findings suggest an intercellular communication–driven mechanism rather than a systemic inflammatory response and, in addition to current ctDNA-based liquid biopsy biomarkers, point to a novel, simple, and highly robust approach for the early detection of cancer. Using this phenomenon to advance PBMC-based biomarker development, it will be essential to achieve 3D in vitro tumor models that reproduce a highly physiological tumor microenvironment (TME). Likewise, more enhanced 3D ex vivo models are required to enable the replication of cell-to-cell and organ-to-organ communication. These systems will guide the self-organization of mixed microenvironments derived from different tissues and enable them to accurately reproduce the molecular connections underlying these alterations. In this study, an innovative new modular 3D co-culturing approach was used to expose PBMCs to lung tumoroids, under physiologically relevant conditions. Changes in DNA fragmentation of PBMCs in the presence of lung cancer were quantified and used as a biomarker. To validate the predictiveness of this biomarker, our results were compared with clinical data from a clinical evaluation study. Similar to the clinical trial observations, PBMCs, when exposed to lung tumoroids, showed a significantly lower level of DNA fragmentation (37%). This modular 3D co-culturing model showed a predictiveness of the clinical data of > 90%, demonstrating its power to monitoring cell-to-cell communication effects and support the development of blood-based biomarkers.

Intravascular Laser Irradiation of Blood (ILIB) on Sleep Quality Improvement: A Randomized Placebo-Controlled Clinical Trial

May 2026 DOI 10.14302/issn.2574-4518.jsdr-25-5773
Peres de Sousa LucasCorresponding author

Introduction Sleep quality is a fundamental determinant of human health and well-being. Modified Intravascular Laser Irradiation of Blood (ILIB), a non-invasive therapeutic modality, has emerged as a potential intervention for sleep-related disturbances. Proposed mechanisms include reduced blood viscosity and platelet aggregation, activation of superoxide dismutase, increased oxygen bioavailability, enhanced microcirculation, elevated serotonin levels, and decreased cortisol concentrations—physiological processes intricately involved in sleep regulation, mood modulation, and the stress response. Objective To evaluate the effects of Modified Intravascular Laser Irradiation of Blood (ILIB) on sleep quality in individuals with self-reported sleep disturbances. Methods A randomized, placebo-controlled clinical trial was conducted with participants who reported poor sleep quality. Subjects were randomly assigned to one of two groups: the intervention group received ILIB using a 660 nm red laser, while the control group received a placebo treatment (light emission with sub-therapeutic power, <1 mW). Both groups underwent the same treatment schedule. Sleep quality was assessed at baseline and after six treatment sessions using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Results Participants in the ILIB group showed statistically significant improvements in the primary outcome of global sleep quality. PSQI scores decreased from 10.24 at baseline to 6.47 post-treatment. ESS scores showed a non-significant change from 10.44 to 10.12. These results suggest enhanced overall sleep quality and reduced sleep latency, although the observed reduction in daytime sleepiness did not reach statistical significance. Conclusion Modified Intravascular Laser Irradiation of Blood appears to be a promising non-invasive approach for improving sleep quality. The clinical outcomes observed are comparable to those reported in both pharmacological and behavioral sleep interventions, particularly in terms of PSQI improvements. These preliminary findings support the need for further research to clarifyunderlying mechanisms, optimize treatment parameters (e.g., dosimetry and duration), and expand outcome assessments to include biomarkers and polysomnographic data.

Obesity Management Open Access

A New Model of Body Composition: Concept and Design Features of the DBA-Model

Apr 2026 DOI 10.14302/issn.2574-450X.jom-26-6138
Dahlmann NicolausCorresponding author

Indices, based on data such as height and weight in general and in particularly the body mass index (BMI), are often used to assess overweight. However, there is limited capacity to differentiate the amount of fat mass between individuals. This review refers to an anthropometric model called Dahlmann-Body-Analysis (DBA), which uses simple anthropometric parameters to define a Reference Weight (Ref-Wt). It is based on hand circumference as a proxy for the skeletal frame and, in addition, the circumference of the abdomen as a proxy for central obesity. Processed through a network of algorithms, the DBA model enabled to differentiate the Difference Weight – that means the difference between the Actual Weight and the Reference Weight – into fat mass and skeletal muscle mass. The DBA-model resembles the 2-component model of Albert R. Behnke, which he considered as a living functional construct including essential fat. The DBA-model matches with Behnke`s 2-component model insofar, as the essential fat is replaced by a physiological amount of fat tissue. The review summarizes studies to compare DBA-derived data with Metropolitan Life Insurance tables, evaluates DBA-derived fat tissue mass with bioelectrical impedance analysis (BIA) derived results and analyses the meaning of the DBA model in clinical settings to uncover the underlying mechanisms of metabolic syndrome (MetS) pathogenesis with increasing amounts of fat mass. The model offers the opportunity to calculate changes in fat or muscle tissue in an absolute (kg) or relative (%) amount on individuals. The data suggest that the DBA-model has satisfactory prediction qualities for use as a practical tool in public health care.

Human Psychology Open Access

Honour and Shame as Moral-Emotional Identity Regulation in Diaspora: An Interpretative Phenomenological Analysis of Young British South Asian Women

Apr 2026 DOI 10.14302/issn.2644-1101.jhp-26-6100
Asif-Malik AmanCorresponding author

Honour and shame are central moral constructs within many South Asian communities, yet their psychological internalisation in diasporic contexts remains underexamined. This qualitative study explored how young British South Asian women (aged 18–25; N = 6) understand and negotiate honour in relation to gender, religion, and identity. Semi-structured interviews were analysed using Interpretative Phenomenological Analysis. Six interrelated themes illustrated honour as a gendered and relational system sustained through anticipatory shame, behavioural surveillance, and sexual double standards. Participants described internalised self-monitoring, bicultural identity tension, and strategic resistance through selective compliance and religious reinterpretation. We propose that honour and shame in minority diaspora contexts function as a moral-emotional identity-regulation system characterised by anticipatory shame, relational accountability, and boundary maintenance under racialisation. This conceptualisation advances acculturation and bicultural identity frameworks by arguing that moral emotion, particularly anticipatory shame, functions as a primary mechanism of cultural internalisation, rather than merely an outcome of value endorsement. The findings further illuminate how moral surveillance shapes identity negotiation and psychological wellbeing, with implications for culturally responsive community and clinical practice.

A Review and Update on the Biochemical Basis of Conscious Breathing (Pranayama)

Mar 2026
Aulesa CarlosCorresponding author

Breathing has long been recognised as a vital process in Eastern traditions such as YOGA and Ayurvedic medicine, where Pranayama is regarded as a transformative practice that harmonises body and mind. While the East developed sophisticated systems of breath regulation for health and self-awareness, the West largely overlooked their significance until the late 19th and early 20th centuries. A group of pioneering physicians, sometimes referred to as "the pulmonauts", including Christian Bohr, Konstantin Buteyko, and Peter M Litchfield, explored the physiological foundations of respiration. They emphasised the benefits of slow, nasal breathing and its relationship to both physical and emotional well- being. In the 21st century, contemporary researchers and practitioners such as James Nestor, J. Patrick McKeown and Anders Olsson have expanded this understanding through the fields of biochemistry, physiology, and biomechanics. Their work has clarified the mechanisms underlying conscious breathing and refined ancient pranayama techniques. Integrating insights from both Eastern and Western traditions reveals that breathing is a central factor in maintaining homeostasis and emotional balance.

Evolutionary Science Open Access

Interactions Between Natural Nuclear Reactors and Microbial Evolutionary Processes

Feb 2026 DOI 10.14302/issn.2689-4602.jes-25-5926
Easttom ChuckCorresponding author

The impact of ionizing radiation on genetic change is well established, yet the extent to which naturally occurring radiation fields have influenced evolutionary trajectories remains incompletely understood. This study examined correlations between microbial evolution and the radiation and geochemical environments associated with natural fission reactors, with emphasis on the Oklo–Bangombé system in present-day Gabon, Africa. The current paper compares plausible doserate regimes adjacent to reactor zones with published observations of radiationinduced phenotypes, geneexpression changes, and repair strategies in model organisms and complex biotas. This study further considers indirect mechanisms (e.g., water radiolysis, redox restructuring, tracemetal mobilization) by which natural reactors could have modulated ecological selection pressures over long timescales. The synthesis supports the plausibility of three interacting pathways: (i) increased mutation supply under low, chronic dose rates; (ii) selection in oxidantrich, redoxstratified niches; and (iii) metabolic subsidies (e.g., H₂) from radiolysis that support chemotrophic guilds. Although temporal–spatial associations exist between reactor activity and biological innovations preserved in Paleoproterozoic strata of Gabon, current evidence remains correlational rather than demonstrably causal. The study further outlines testable predictions and experimental designs capable of discriminating among these mechanisms.

Veterinary Healthcare Open Access

The Effects of L Carnitine on in Vitro Maturation of Immature Bovine Oocytes

Dec 2025 DOI 10.14302/issn.2575-1212.jvhc-24-4889
A Elmetwally MohammedCorresponding author

L-Carnitine (Lc) acts as an antioxidant that neutralizes free radicals, especially superoxide anions and protects cells against oxidative damage-induced apoptosis, as following ovulation, intracellular reactive oxygen species (ROS) accumulation increases in oocytes, Oocytes exhibit an intracellular defense mechanism against an oxidative attack. This outcome adversely affects fertilization and subsequent embryonic development, thereby increasing the risk of an early miscarriage and abnormal development of offspring. The purpose of this study was to see how adding LC to either maturation or fertilization medium affected the developmental competence of immature bovine oocytes. In this study, Ovaries from apparently normal reproductive organs of cattle were collected within 30 minutes from slaughter and evisceration of animals. Cumulus oocyte complexes (COCs) were collected by aspiration of medium sized ovarian follicles (4-8 mm). COCs of acceptable quality were selected, washed and incubated in tissue culture media 199 (TCM199) supplemented with 10% heat inactivated fetal calf serum, 5 μg/ml luteinizing hormone (LH), 0.5 μg/ml follicle stimulating hormone (FSH) and 1 μg/ml estradiol-17β for 20:22 hour at 38.5 C◦ under 5% CO2 in air with 90% humidity. different concentrations of LC (1.25,2.5 and 5mM) were used. The results were consistent for both maturation and fertilization and there is a significant increase in maturation, fertilization., cleavage and blastocyst rate. In conclusion, LC has important role in IVEP through addition of LC to maturation media or culture media it improved nuclear maturation and blastocyst formation rates in bovine oocytes.

Cervical Cancer Open Access

Review: The Role of Human Papillomavirus in Virus-Induced Carcinogenesis

Dec 2025 DOI 10.14302/issn.2997-2108.jcc-25-5657
M Essam ZahraaCorresponding author

Viral infections contribute to a significant proportion of human cancers, with human papillomavirus (HPV) being one of the most well-established oncogenic viruses. This review summarizes HPV biology, transmission, classification, molecular mechanisms of carcinogenesis, epidemiology of HPV-associated cancers, and current and emerging preventive and therapeutic approaches. particularly HPV-16 and HPV-18, drives malignant transformation through the E6 and E7 oncoproteins, which disrupt tumor suppressor pathways p53 and Rb. Prophylactic vaccination programs have demonstrated remarkable success in reducing HPV-related disease burden, but disparities in coverage remain. Cutting-edge strategies such as CRISPR/Cas9 and RNA-based therapeutics offer promising avenues for treating established infections. Integrating these biomedical advances with robust public health initiatives is essential to ultimately eliminate HPV-associated cancers worldwide (Figure1).

Embryology Open Access

Molecular Control of Human Embryonic Development: A Comprehensive Study

Nov 2025 DOI 10.14302/issn.3070-5657.je-24-5327
Khanday ShifanCorresponding author

Human embryonic development is a highly coordinated and complex process that transforms a single fertilized cell into a fully formed human organism. This process is governed by intricate molecular mechanisms involving genetic regulation, signal transduction pathways, and intercellular communication. This study explores key molecular pathways controlling human embryonic development, focusing on the roles of morphogens, transcription factors, signaling molecules, and epigenetic modifications. By reviewing the most recent literature and experimental studies, we aim to highlight the molecular orchestration that directs cell fate decisions, tissue patterning, and organogenesis in humans.

Human Psychology Open Access

The Human Soul as a Manifestation of Quantum-Like Fields

Oct 2025 DOI 10.14302/issn.2644-1101.jhp-25-5737
W. Kamen EdwardCorresponding author

It is proposed that the human soul is a manifestation of a soul field consisting of a collection of quantum-like fields. The soul field interacts with the electromagnetic field, manifested by photons interacting with the quanta of the soul field. Evidence for this comes from near-death experiences where reported events that could not have been seen through the eyes of the individual are verified. Since bioelectric fields are a type of electromagnetic field, bioelectric fields may also interact with the soul field. This could result in the transfer of information on working memory content to the soul via interactions with bioelectric fields produced by neural ensembles in the human brain. The soul field may also affect neurons on the molecular level in the brain through interactions with bioelectric fields and the recently proposed mechanism of cytoelectric coupling. The human soul is coupled to the body through its interactions with bioelectric fields in the body. Manifestations of the quantum-like fields comprising the soul field may carry out different functions such as encoding memories and experiences, representing emotion states, and defining personal identity. Interactions of these fields and their quanta could produce emergent properties such as self-awareness and consciousness.

ADHD And Care Open Access

The Relationship Between Abnormal Sleeping Patterns and ADHD

Jan 2025 DOI 10.14302/issn.3066-8042.jac-24-5273
Davis JuliaCorresponding author

The objective of this focused literature review includes establishing and explaining the high correlation between sleep issues and ADHD. Through a systematic review of sources, a high correlation between sleep issues in those with ADHD was established with multiple theories lending explanation to this comorbidity. Neurological pathways in the brain already afflicted by the disorder of ADHD may cause direct effect on sleep pathways in their dysfunction. Other comorbid sleep conditions were found to occur in high frequency with ADHD however, a common etiology of these issues is yet to be established. The major conclusion of this study includes that there are multiple mechanisms through which sleep disturbances may be caused in ADHD patients, all of which must be considered in future research.

Identity Reorganization Among Primiparous Cameroonian Adolescents: From the Status of Daughter to the status of Mother

Dec 2024 DOI 10.14302/issn.2474-9273.jbtm-24-5317
Ndje Mireille NdjeCorresponding author

Adolescence in Cameroon, as in many parts of sub-Saharan Africa, is often marked by early childbearing. Studies have shown a national prevalence of adolescent deliveries to be around 14.2% - 14.4%, a higher rate than the average for sub-Saharan Africa This presents a unique challenge for young mothers, who must navigate the complex process of identity reorganization while still navigating their own adolescence with its multiple changes. This article explores the experiences of primiparous (first-time) Cameroonian adolescents as they transition from daughters to mothers. The objective of this article is to understand how identity reorganization takes place among primiparous Cameroonian adolescents who pass without transition from the status of daughter to the status of mother. Drawing on qualitative data from semi-structured interviews, with seven participants chosen on the basis of selection criteria, the article examines the psychological, social, and cultural factors that shape this identity shift. An interview guide with three main themes made it possible to collect verbatim comments from the participants. The thematic analysis highlights the challenges faced by these young mothers, such as navigating social stigma, managing emotional upheaval, and balancing motherhood with their own developmental needs. The findings of this study highlight the complex and multifaceted nature of identity reorganization among primiparous Cameroonian adolescents. The social stigma associated with early childbearing, coupled with the emotional and practical demands of motherhood, can pose significant challenges to these young women. However, a study on a larger sample could reveal the resilience and resourcefulness of some adolescents, who find support within their communities and employ various coping mechanisms to navigate this transition. Finally, the article discusses the implications of these findings for adolescent maternal health interventions and social policy in Cameroon.

The Role of Cerebral Hypercarbia in the Induction of the Near-Death Experience

Dec 2024
A Shaw NigelCorresponding author

The near-death experience (NDE) is an altered state of consciousness which arises when a person is critically ill or injured and possibly clinically dead. It should not be conflated with other mental events such as the deathbed vision or the fear or anticipation of death. Many believe that the NDE represents a genuine paranormal phenomenon providing a glimpse of an otherworldly existence and proof of an afterlife. Those who are skeptical of such a survivalist or supernatural interpretation have long pointed out that the core components of the NDE can be readily simulated with a variety of states, conditions and agents. In this conception, the NDE is reduced to no more or less than an extraordinarily complex hallucination. Since its rediscovery in the 1970s, multiple, often ingenious, attempts have been made to account for the NDE in such naturalistic or neuroscientific terms. None has so far proven completely satisfactory. One of the oldest, least considered but still promising is the CO2 theory which argues that a hypercarbic brain is a necessary precursor for the induction of a NDE. Supportive evidence that CO2 does play a pivotal role in the generation of the NDE can be gathered from diverse sources. These include: 1. measurement of blood gases; 2. Meduna’s now abandoned CO2 therapy; 3. analysis of the very limited number of pathophysiological conditions underlying the NDE; 4. recent discoveries of the role of 5-HT neurons in the central respiratory system. A model is proposed in which CO2 molecules are considered to be functionally equivalent to those of the classical hallucinogens (LSD, mescaline, psilocybin, dimethyltryptamine). These agents can mimic the phenomenology of the NDE with remarkable fidelity. What is still missing from any such explanation is the long-sought transduction mechanism which converts physical events into mental ones. This is a generic problem which confronts all attempts to explain the neurogenesis of mystical, psychedelic or visionary activity.

Ophthalmic Science Open Access

Glaucoma Literacy in a Portuguese Population

Dec 2024 DOI 10.14302/issn.2470-0436.jos-24-5322
Pestana Aguiar CatarinaCorresponding author

Studies show that individuals with limited health literacy skills experience worse health outcomes in a multitude of chronic diseases including glaucoma. These patients have poorer compliance, worse disease understanding and greater disease progression. The main purpose of our study was to evaluate the knowledge about glaucoma basic concepts in patients with this disease. A 24 question survey was given to patients followed by the glaucoma department, by phone or in person. Epidemiological data and personal therapeutic regimens were collected as well as data concerning the pathophysiology, treatment and prognosis of the disease. Survey responses were obtained from 79 patients with a mean age of 72 years old. Most of the patients had a low education level. The majority of patients could not enumerate glaucoma risk factors (74.5%), their glaucoma type (94.9%) or the best glaucoma definition (57%). However, they were able to relate the disease to a high IOP (75.9%) and the possibility of it leading to blindness (96.2%). We believe that patients, when observed in their glaucoma appointments, tend to retain information related to the prognosis and consequences of the disease and not focus on the understanding of its pathophysiology, causes and mechanisms, which may reflect their concern about their own future. However, this may lead to some misconceptions about the definition of glaucoma and specially about what can cause this disease. Some investment should be done to improve health literacy in the glaucoma population, with appropriate language and handed material.

Creation of Music-Induced Analgesia in Chronic Pain Patients through Endogenous Opioid Production: A Narrative Review

Oct 2024 DOI 10.14302/issn.2688-5328.ijp-24-5319
Puri NivritiCorresponding author

Chronic pain affects over 30% of the global population, and reliance on external drugs for treatment has led to major issues, including the present opioid epidemic. A healthier option is necessary, which is why music therapy’s analgesic effects have been extensively studied within the last 20 years. Not only is music relatively harmless but given that chronic pain patients require repeated treatment, musical intervention is far more accessible and economical. While the mechanisms underlying music-induced analgesia are relatively unclear, the production of endogenous opioids while listening to music through both the descending pain modulatory circuit and the limbic system, is postulated to play this role. This review describes the brain regions and pathways by which music may trigger the release of endogenous opioids such as enkephalins, endorphins, and dynorphins. More importantly, it discusses the cellular mechanisms through which these neuropeptides are thought to mediate pleasure-induced analgesia in chronic pain patients.

Ophthalmic Science Open Access

A Network Pharmacology-Based Strategy For Predicting Therapy Targets Of Beta-Sitosterol In Treating Diabetic Retinopathy

May 2024 DOI 10.14302/issn.2470-0436.jos-23-4493
Sun KexinCorresponding author

Background Beta-Sitosterol (SIT) is an active TCM compound employed to treat diabetic retinopathy (DR). A network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying DR has not been pursued. Methods The potential targets for DM were identified according to the MedGene, Gendome, HGNC, OMIM, GeneCards, PheGenI, GEO, and STRING database. The herb and components were predicted and screened by network pharmacology through oral bioavailability and drug-likeness filtration using the Traditional Chinese Medicine Systems Pharmacology Analysis Platform database. A network pharmacology prediction and network analysis were used to predict the active potential targets and pathways of SIT application to DR. Results We found the Top 15 DR-related genes by screening in 9 databases. 26 kinds of TCM and nearly 300 kinds of active ingredients. SIT exists in 10 kinds of DR-treat TCM. The comprehensive network pharmacology approach was successful in identifying 23 kinds of core genes for SIT treating DR. ERBB3 and IGF2-related PI3K-Akt signaling pathway or EDN3, IGF2 and SPP1-related receptor ligand activity pathway might be the main pharmacological targets, and pathways in DR. We speculated that SIT was effective for the treatment of DR.  Conclusion Based on the network pharmacology, we predicted the potential targets of SIT in treating DR and helped to illustrate the mechanism of action. Our study identifies key genes and pathways associated with the prognosis and pathogenesis of DR from new insights.

Stereoselective Synthesis of N-Glycosyl Oxazolines and Evaluation of Their Antiproliferative Activity

Dec 2023 DOI 10.14302/issn.2377-2549.jndc-23-4740
G. Sivets GrigoriiCorresponding author

A stereoselective synthesis of protected N-glycosyl oxazolines has been developed from available acylated sugar 1,2-O-acetonides using intramolecular Ritter-like reactions. New N-α- and β-D-pentofuranosyl, α-D-hexofuranosyl oxazolines as valuable intermediates for preparation of diverse N-glycosides were obtained by BF3.OEt2-KHF2 or BF3.OEt2-promoted reactions of pentofuranose and hexafuranose acetonide derivatives with nitriles. When selectively acylated D-xylo- or ribofuranoses were employed in the reactions, N-α-pentofuranosyl oxazolines were prepared in good yields. A mechanism for the formation of glycosyl oxazolines was proposed. A series of oxazoline derivatives were evaluated for their antiproliferative activity on three human cancer cell lines (MCF-7, Hela and K562).

Clinical application of Momordica charantia (Bitter Melon) for reducing blood sugar in type 2 diabetes mellitus

Oct 2023 DOI 10.14302/issn.2379-7835.ijn-23-4737
J. Johnson JeremyCorresponding author

Bitter melon is a popular fruit cultivated in Southeast Asia and other tropical climate regions. Bitter melon has been used in traditional medicine because of its numerous medicinal benefits, including having hypoglycemic effects. This has an indication for diabetic patients, and several clinical trials have provided evidence that orally administered bitter melon extract can reduce A1C and blood sugar levels in diabetes patients. In vitro and in vivo mechanistic studies suggest that bitter melon’s anti-diabetic actions work through intra- and extra-pancreatic mechanisms. Herein we summarize and highlight these mechanistic and clinical studies that have demonstrated the hypoglycemic effects of bitter melon in type 2 diabetes patients.

Human Health Research Open Access

Assessment of the Factors that Contribute for the Cause of Asthma Disease in Ambo Town

Apr 2023 DOI 10.14302/issn.2576-9383.jhhr-22-4259
Bekele DamtewCorresponding author

Asthma is a chronic disease of airways; that is widely characterized by an increased responsiveness to a large variety of stimuli, airway inflammation and obstruction. It is the most common respiratory disorder disease in developed and developing countries. The study was aimed to assess the factors that contribute for the cause of asthma disease in Ambo town and cross-sectional survey was conducted to gather information from March to April 2022. 30 respondents were selected using purposive sampling technique for interview and data collections. According to the study the more affected age group were 22-32(53%) and the major risk factor for the disease was air pollution (53%). The pollution is due to domestic wastes that are discharged to the environment. Therefore, the government and extension health workers should aware the community about the risk factors of asthma and proper waste disposal mechanisms.

Evolution of Janus Kinase 2 V617F-negative idiopathic myelofibrosis into Philadelphia+ chronic myeloid leukemia

Mar 2023 DOI 10.14302/issn.2641-5518.jcci-23-4506
Partanen AnuCorresponding author

Limited data exist on the mechanisms promoting clonal expression of BCR-ABL1 cells in various myeloproliferative disorders. We present a patient whose Janus Kinase (JAK) 2 V617F-negative idiopathic myelofibrosis (IMF) transformed to Philadelphia-positive chronic myeloid leukemia (CML). A 55-year-old man had anemia and splenomegaly. Trephine biopsy showed excess fibrosis without a JAK2 V617F mutation. Diagnosis of high-risk IMF with t(3;12) and del(16q) was made. Five years later a repeated trephine biopsy showed extensive fibrosis and t(9;22) with der(22)t(9;22). BCR-ABL1 fusion gene with typical p210 fusion transcript was found resulting in the diagnosis of CML. A modest treatment response was achieved with tyrosine kinase inhibitor (TKI) therapies, but the disease eventually progressed to a myeloid blast phase. With AML-based chemotherapy plus azacytidine and a second generation TKI the patient survived for years but succumbed 11 years after the initial diagnosis. Clonal evolution may cause atypical disease characteristics or a poor response to targeted therapy in myeloproliferative disorders.

Human Health Research Open Access

A Note from the Field “Potlatch” Advancing a Health Survey: The Pen is Truly Mighty

Dec 2022 DOI 10.14302/issn.2576-9383.jhhr-22-4397
J Johnson RalphCorresponding author Research PA-C/Research Coordinator, University of Texas MD Anderson Cancer Center

Despite vast improvements in chemo-therapeutic interventions extensively extending the life span of patients with chronic and terminal diseases, there also is the unhappy extension of side- effects and adverse events. Thus, Health-Related Quality of Life (HR-QoL) becomes equally as important as length of life. Accurately, reliably, validly, and representatively measuring the on-going pulse beat of HR-QoL means ensuring optimal responses and response rates, which in turn means fostering and maximizing Survey Participants’ continued rapport, enlistment, engagement, and participation regarding HR-QoL research survey studies. This is generally true regarding all human subjects’ research. HR-QoL survey work at a nationally renowned Cancer Center recently identified an example of Potlatch or gift-giving (i.e., gifting), and its surrounding nuances, that were calculated and appear to evoke enhanced reciprocal engagement in a HR-QoL survey. This work involves continuous, iterative marketing study. The intent of this field note is to describe the methodological phenomenon that may have epistemological and theoretical relevance for ubiquitously advancing the interest of health survey research. Specifically, the contention will be that considered, and tactically deployed Potlatch can serve as a mechanism for facilitating and enhancing health survey research as well as enhancing stronger social engagement in research and treatment for patients undergoing medical care for long-term, chronic illness. First, it can rejuvenate and refocus Survey Participants’ involvement. Second, it can serve as an entrée and springboard to further forge a social connection in the interest of research. Lessons Learned and implications are reported.

Correlating 13C Isotope in Oligomeric Proanthocyanidins with their Anticancer Properties

Oct 2022 DOI 10.14302/issn.2572-3030.jcgb-22-4284
B. Little ReginaldCorresponding author Department of Chemistry, Stillman College, Tuscaloosa, Alabama

Upon considering the anticancer effects of larger oligomeric proanthocyanidins and observing various papers reporting the high resolution mass spectroscopy of the oligomeric proanthocyanidins, it is determined that the unusual 13C enrichment in some plant oligomeric proanthocyanidins may be responsible for the anticancer activities of these food products. Such correlation of the 13C in the oligomeric proanthocyanidins also correlate with their scavenging of free-radicals, anti-virial and anti-bacterial properties. Proanthocyanidins in grape seeds are observed to have high enrichment in heavy isotopes of 2H, 13C, 15N and/or 17O. Mass analysis of DNA from human cancer cells are compared to normal human cells and cancer cells show bond specific enrichment of heavy isotopes in nucleotides G, A, T and C. On such basis, this study suggests possible stronger interactions of proanthocyanidins with DNA in cancer verses DNA in normal cells due to heavy isotope bond specific enrichments in both proanthocyanidins and the cancer DNA. Such 13C interactions from oligomeric proanthocyanidins with nucleic acids and proteins involved in replications, transcriptions and translations in cancer cells for interacting and chemically altering anabolism and cell division of the cancer cells are consistent with the author’s mechanism for normal cell to cancer cell transformations via possible replacements of primordial 1H, 12C, 14N, 16O, and 24Mg isotopes by nonprimordial 2H, 13C, 15N, and 17O and 25Mg isotopes in the proteins and nucleic acids. Such is also consistent with the proposed treatment for cancer by the author by use of foods containing proteins, nucleic acids, carbohydrates and/or drug molecules enriched with the nonprimordial isotopes of 2H, 13C, 15N, and 17O and 25Mg.

Syntheses of Clofarabine and Related C2′-β-fluorinated Nucleoside Analogues

Sep 2022 DOI 10.14302/issn.2377-2549.jndc-22-4277
Sivets GrigoriiCorresponding author Institute of Bioorganic Chemistry, National Academy of Sciences, 220141 Minsk, Acad. Kuprevicha 5/2, Belarus.

A multistep synthesis of 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine (clofarabine) is described from methyl β-D-ribofuranoside. A new improved method for preparation of 1,2-diacetyl D-ribofuranose derivative was developed via acetolysis of tri-O-pivaloylated D-ribofuranoside and plausible mechanism of the reaction was proposed. Synthesis of 3′,5′-di-O-pivaloyl-2,6-dichloropurine β-D-riboside along with isomeric 2′,5′-di-O-pivaloyl nucleoside was carried out by stereoselective glycosylation reaction of 2,6-dichloropurine with peracylated D-ribofuranose followed by regioselective 2´-O-deacetylation of protected β-ribonucleoside with different bases. Mild C2′-β-fluorination of the purine 3′,5′-di-O-pivaloyl ribonucleoside with an excess of diethylaminosulfur trifluoride afforded protected 2,6-dichloropurine 2′-fluoro β-D-arabinoside as the key intermediate. Efficient route to clofarabine was also investigated using anion glycosylation of 2-chloroadenine potassium salt with the 1-α-bromide and potassium tert-butoxide in binary solvent mixture, chromatography for separation of a mixture of anomeric nucleosides (a β/α ratio of 3.0:1) and deacylation of benzoylated 2′-fluoro β-nucleoside. Novel N6-isopentyl clofarabine analogue was synthesized by a direct alkylation of the parent nucleoside

Computational Systemic Biology for Toxicity Studies: A Mini Review of Previously Published Articles

Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
Tariku Belay YilkalCorresponding author School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda

The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.

Osteoarthritis and Neuromuscular Deficits: Can a Causative Role be Discounted- Key 2017-2022 Observations

May 2022 DOI 10.14302/issn.2474-7785.jarh-22-4191
Marks RayCorresponding author Department of Health and Behavior Studies, Columbia University, Teachers College New York, USA.

Background The origin of osteoarthritis, the most common disabling disorder of older adults remains uncertain. Aim This mini review examines the possible role played by various neuromuscular deficits in the osteoarthritis etiopathogenic process. Methods and Procedures Articles that haveaddressed the current topic of interest and were located in the PUBMED,Google Scholar, and Web of Science electronic data bases as of 2017-2022 were carefully sought and examined. Results Various neuromuscular mechanisms may have a bearing on the development and progression of osteoarthritis, but the data are largely unrelated and observational in nature. Conclusion More research to examine this issue is sorely needed and could have considerable merit in light of the growing populations of older adults at risk for disabling osteoarthritis in the face of few intervention options to help them to achieve an optimal functional level.

Thin Film Deposition and Characterization Techniques

Apr 2022 DOI 10.14302/issn.2831-8846.j3dpa-22-4066
Geremew TemesgenCorresponding author Debark University, Department of physics, Debark, Ethiopia

Thin films are everywhere in the modern world, with many of the technologies we depend upon in daily life being, in turn, dependent upon thin film technology. Chemical bath deposition includes principles of chemical bath deposition (CBD) and concept of solubility product, nucleation and film growth, thin film deposition mechanism in chemical bath deposition. The non-metallic ion source (anions) and metal ion source (cations) then react to form the compound. The nucleation process plays an important role in determining the crystallinity and microstructure of the resultant film. From the discussion of deposition techniques which are physical and chemical deposition methods. Physical deposition techniques contains sputtering deposition, electron beam evaporation and physical vapour deposition (PVD) process have been known for over 100 years and also fabrication films on the substrate, as well as the increasement of the pressure in the chamber due to operation of the sources indicates directly that gases or vapors are desorbed. Chemical deposition process is economically effective and has been industrially exploited to large scale. It can be summarized that thin film characterization techniques include X-ray diffraction (XRD), UV-Vis spectrophotometer, scanning electron microscopy, energy dispersive x-ray diffraction, transmission electron microscopy (TEM). X-rays diffraction (XRD) is a rapid and a powerful technique used to study the phase of a crystalline material, information on unit cell lattice parameters, crystal structure, crystal orientation and crystalline size.

A Patient with Monoclonal Gammopathy of Undetermined Significance and Detected Philadelphia Chromosome

Apr 2022 DOI 10.14302/issn.2372-6601.jhor-22-4133
Qing XinCorresponding author Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.

Background Monoclonal gammopathy of undetermined significance (MGUS) and chronic myeloid leukemia (CML) are diseases of different lineages. The diagnosis of both MGUS and CML in the same patient is a rare occurrence and has not been reported in much literature. Case Presentation We describe a 56-year-old man with a history of rheumatoid arthritis incidentally found to have an increase in IgA paraprotein. With less than 10% monoclonal plasma cells on the bone marrow biopsy and absence of hypercalcemia, renal failure, anemia and bone lesions, MGUS was diagnosed. The conventional cytogenetics at the time showed the presence of the Philadelphia chromosome in 30% of metaphases. However, there was no morphologic evidence of CML in the peripheral blood or bone marrow. Patient received no treatment and lost follow-up until 3 years later when a routine CBC showed leukocytosis and thrombocytosis. CML, chronic phase was diagnosed following a bone marrow aspiration and biopsy with Philadelphia chromosome observed in 100% of metaphases. Patient was treated with imatinib and later switched to dasatinib and complete molecular remission was continued to be achieved. Discussion and Conclusion Here we report a case of pre-leukemic CML as an incidental finding during the diagnosis of MGUS. The possible underlying mechanisms of the association are discussed although the exact cause of the coexistence is unclear.

What is known Today about Nutrition and Microbiota

Mar 2022 DOI 10.14302/issn.2379-7835.ijn-22-4120
Mainardi PaoloCorresponding author People's University for Food and Health Studies, Genova, Italy.

We are experiencing years of profound cultural revolution. New insights into the microbiota upset concepts in physiology, medicine, and nutrition. The role of the microbiota for our health is increasingly evident. We are increasingly certain that our health depends on that of the microbiota, or, rather, on its strength in controlling the physiology of body organs, the mechanisms of repair and protection. It is not so much a pathogen that makes us fall ill, but a reduced ability to protect and repair ourselves from damage produced by pathogens that affect us continually. Current knowledge leads us to a new medicine aimed at curing the microbiota so that it can (come back to) take care of us. In this new medicine, food rediscovers a fundamental role, since it is the best way to communicate with the microbiota, to modulate and strengthen it. And it is curious how the most recent acquisitions bring us back to the past, to an ancient medicine, which we had forgotten after the discovery of drugs, imagined capable of acting on complex pathogenetic mechanisms. By acting, more simply, on the microbiota we can activate powerful endogenous mechanisms, which keep us healthy, when we are, more powerful than any drug we can invent. Now there is nothing left to do but apply the new knowledge.

Expression of Concern: Potential Risks and Unknown Effects of mRNA Vaccines on Population Health (6th Rev). Damages Are Being Materialized

Mar 2022 DOI 10.14302/issn.2692-1537.ijcv-22-4117
Wu JianqingCorresponding author Healthier World (Independent researcher for cause), P. O. Box 689, Beltsville, MD 20704. USA

Several mRNA vaccines are used on the population in the U.S. I started predicting the dangers of mRNA vaccines before March 2021 and update my findings periodically. My prior model study enabled me to identify many flaws in clinical trials, side-effect evaluation methods and mechanism studies, and I also considered consistent failure in predicting drug side effects in the past and systematic failure of FDA in keeping out dangerous drugs from market. I found that the risks of vaccination cannot be determined by experiments alone and must be determined by using a combination of methods. By studying mRNA expression dynamics and kinetics, I predict that vaccination with mRNA vaccines may increase cancer risks, multiple organ failure risks, earlier death risks, genome alteration speeds by one or more mechanisms, alter the normal selection process for viral evolution resulting in more virulent viruses, and aggravate chronic diseases or cause healed diseases to relapse. Two root problems are practical inability to control expression sites and severe adverse reactions from repeated vaccination. Based on mRNA bio-distribution, the mRNA mainly strikes the liver and other vital organs, and poses grave dangers to persons whose vascular functional reserves are relatively small, or whose vascular systems are temporarily burdened by other causes such as viral infections or life activities. If an mRNA vaccine is administered on a pregnant woman by second or booster shots, spike protein synthesis in fetus brain disrupts the highly regulated protein synthesis processes, resulting in potential brain damages. In less than a year, most of my early predicted damages are being materialized or are on the track to hit the population. In this update, I present a benefits-and-risks map to show how the number of deaths caused by mRNA vaccines is grossly underestimated and why claimed benefits like 95% effectiveness rate and 90% death rate reduction are meaningless and misleading.

Nephrology Advances Open Access

Thyroid Function Abnormalities in Patients with Chronic Kidney Disease

Feb 2022 DOI 10.14302/issn.2574-4488.jna-21-4039
K Al Miraj ACorresponding author Research Assistant, Department of Vascular Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU)Dhaka, Bangladesh.

The function of the thyroid gland is one of the most important in the human body as it regulates the majority of the body's physiological actions. The thyroid produces hormones (T3 and T4) that have many actions including metabolism, development, protein synthesis, and the regulation of many other important hormones. There is a lot of interaction between the kidney and thyroid gland during the disease States thyroid hormones have a major role in regulating the glomerular filtration rate through its hormonal actions in normal physiology. But these things are altered in the disease States such as chronic kidney disease. It is a well-known fact that hypothyroidism causes decreased Glomerular filtration rate whereas hyperthyroidism causes increased Glomerular filtration rate leading to renin-angiotensin-aldosterone system activation. In our study we aim to see the prevalence of low T3 syndrome in different stages of CKD which is a state of physiological benefit in preserving the proteins lost through the Kidneys in CKD patients and since CKD is progressed in hyperthyroidism state it is a protective mechanism in restoring the CKD status. Other subclinical hypothyroidism hyperthyroidism. Autoimmune hypothyroidism. Glomerulonephritis are all part of a dynamic endocrine and nephrology sequence. Thorough knowledge of these is required for optimum treatment of thyroid in CKD patients.

Inferior Turbinate Surgery: Difficulties Between the Decision-Making and the Selection of Proper Technique

Jan 2022 DOI 10.14302/issn.2379-8572.joa-21-3964
Mohamed Bofares KhaledCorresponding author Professor of otorhinolaryngology Omar Almoukhtar University, Elbyda, Libya

Back ground and Objectives The inferior conchae have important role in the maintenance of nasal airflow via providing the nasal valve mechanism but increase of inferior turbinate bulk may result in significant nasal obstruction. Therefore, this may need further surgical intervention to deal with these bulky conchae but it is very necessary to balance between the mechanical as well as the functional patency of the nose. Thus, through this surgery it become difficult to decide whether the patient is a candidate for surgery and which technique is suitable for that particular patient. Patients and Methods Two- thousands three- hundreds and six patients aged 3-65 years of hypertrophied inferior conchae, had been diagnosed as a cases of mechanical nasal obstruction due to hypertrophied inferior conchae (HIC). The patients operated by two techniques of inferior conchae surgery, which are sub-mucosal diathermy (SMD) and partial inferior turbinectomy (PIT). The outcomes were correlated to different factors to assess as much as possible the clear conclusion for this significant issue in rhinology. Results and Conclusion The proper selection of patient for this pattern of surgery is considered as one of main aspects of this issue and one of significant steps toward the resolving of this dilemma it is very necessary to select the most suitable candidate for this surgery. On the other hand, the type of the technique for this surgery is needed to be selected probably.

Photobiomodulation, Depression, Anxiety, and Cognition

Aug 2021 DOI 10.14302/issn.2474-7785.jarh-21-3935
Marks RayCorresponding author Department of Health and Behavior Studies, Teachers College, Columbia University, New York, NY 10027, USA.

Background Anxiety and depression are key barriers to healthy aging and greatly heighten the risk for many negative health issues that seriously impact life quality. Aim This mini review examines the potential of low level laser treatments or photobiomodulation therapy for ameliorating severe anxiety and depression in older adults. Methods and Procedures Articles that adressed the current topic of interest extracted from PUBMED and Google Scholar were carefully and presented in narrative form. Results Photobiomodulation therapy appears to be a safe efficacious modality for ameliorating various degrees of anxiety and depression and for improving cognition, and is supported by several well established mechanisms of action at the molecular, cellular, and tissue levels. Conclusion More research to examine who might benefit most from this form of therapy, and in what respect in this area of growing global concern and few intervention options is strongly warranted.

Impact of COVID-19 on Supply Chains in Zimbabwe

May 2021 DOI 10.14302/issn.2641-4538.jphi-21-3824
Munharo StevenCorresponding author University of Suffolk, Ipswich, UK

Zimbabwe like many other sub-Saharan African states has been struggling to provide a quality health service delivery system. Nations with rampant corruption and ineffective bureaucracy made worse, the response towards the fight against COVID-19, Coronavirus Disease 2019. Despite the Zimbabwean government setting out protocols with international agencies such as WHO, World Health Organization to mount an effective response against COVID-19, the health system has been overstretched with lack of personal protective equipment, shortage of drugs and essential equipment and wanton corruption practices coupled with shortage of staff. Timely delivery of orders is still a challenge due to strict bureaucratic measures when transporting goods and the existing competition between countries. Manufacturers and donors are shifting their focus to their countries leaving the Zimbabwean health service underfunded and under-resourced. However, among the challenges experienced the country has been given a chance to revisit its priorities and strategize how best the government and organizations can move essential medical goods, utilize current trade agreements such as ACFTA, African Continental Free Trade Area and local drug manufacturers to produce essential medicines. Launching an efficient mechanism to end corrupt practices in procurement and supply as well as improve interagency cooperation and communication may help improve efforts to end COVID-19 in Zimbabwe.  

Chirps Amidst Coronavirus Disease-2019 (COVID-19) Transmission and Prevention in Ethiopia in 2020

Apr 2021 DOI 10.14302/issn.2692-1537.ijcv-21-3741
Assegid SahiluCorresponding author MD, MPH, Associate Professor of Epidemiology Jimma University, Jimma, Ethiopia

Background Ethiopia confirmed its 1st case of COVID-19 on Friday 13th February 2020. The burden increased dramatically by August/2020. The conditions that led to this rise were not reviewed. Objective To exploreCOVID-19 related phenomena in Ethiopia during 2019-2020. Materials and Methods Review of journals, books, and letters to editors, e-sources, news, personal experiences, observations, and communications. Results The zoonotic source of SARS- CoV-2 (Severe Acute Respiratory Distress Syndrome- Coronavirus-2) is not confirmed. The precedent events; and exact mechanism of COVID-19 is not clear. Dynamic models were required on the time line of dynamics of COVID-19; dynamics of infectiousness of COVID-19, and mechanism of transmission of COVID-19. Incubatory carriers might have been missed. Screening based on temperature had been problematic. The time spent in the development of diagnostic test for COVID-19 might have contributed to the early spread. Uninterrupted flights to China during the epidemic by Ethiopian Airlines as well as uninterrupted domestic flights; IDP (Internally Displaced People); and others put Ethiopia (and other countries) at great risk. Demographic adjustment may not be applicable for Ethiopia due to lack of census which had to be conducted every 10 year, was conducted only in 2007. This adds to the problem of error projection. The impact of HIV (Human Immuno-Deficiency Virus Disease) and war in Ethiopia before 2000 might have had affected people who would be now old age and who would be at the most risk of death. This made the impact of COVID-19 to appear low as revealed by the lower number of COVID-related deaths in Ethiopia. There were also hesitations inconsistencies in case definitions; implementations of quarantine; and burial regulations. Conclusion Even though uninhibited foreign flight to China as well as domestic flights; inconsistencies in the implementation of regulations pertaining to COVID-19 have contributed to COVID- 19 emergence in Ethiopia, the absence of census; the demographic impact of HIV and war before 2000 might have made the impact of COVID-19 to appear low as revealed by the lower number of COVID-related deaths in Ethiopia. Recommendation Accurate and current evaluation of the impact of COVID-19 in Ethiopia may require the absence of census; demographic consequences of HIV; and war before 2000 into consideration.

COVID-19, and Vitamin D, and Air Pollution Global Epidemics Impact on Older Adults

Dec 2020 DOI 10.14302/issn.2474-7785.jarh-20-3662
Marks RayCorresponding author Department of Health and Behavior Studies, Teachers College, Columbia University, NY 10027, United States

Background Most current Corona virus or COVID-19 pandemic deaths have been found to occur among populations older than 65 years of age, who often suffer from the presence of an array of chronic diseases that may be related to a co-occurring vitamin D deficiency. Another factor affecting older adults’ immune response mechanisms is air quality. In turn, air quality can impact the absorption of vitamin D from sunlight sources, a factor which could explain why older people, who are often vitamin D deficient, may be more likely than younger adults or healthy adults to be at risk for COVID-19 and poor outcomes. Aim This work was designed to examine the recent literature on COVID-19, vitamin D and air pollution and what it might imply for public health workers, policy makers, and others. Methods Available data accessed largely from the PUBMED data base for the year 2020 using the key words COVID-19, air pollution, and vitamin D deficiency were sought and selected items were carefully examined and documented in narrative and tabular formats. Results Many publications on COVID-19 prevail, but far fewer focus specifically on vitamin D deficiency and its possible role in explaining COVID-19 global health risk among older adults. A similar, albeit small number of publications, discuss the global pandemics of air pollution and its possible COVID-19 association, as well as its impact on vitamin D production. However, while most related articles support a possible independent as well as a dual role for both factors in COVID-19 the realm of this highly infectious widespread disease, very few actual studies have been conducted to date on any of these topical issues Conclusion More research to examine if vitamin D-based nutrients or supplements may provide some degree of community wide protection against COVID-19 in the older vitamin D populations, especially among those living in highly polluted areas may prove highly valuable. Controlling air pollution emissions globally and locally may also prove to be a highly impactful public health approach to reducing overall COVID-19 risk, and extent, and warrants study.

Reversible Posterior Encephalopathy Syndrome and Related Factors: Clinical Cases Study

Nov 2020 DOI 10.14302/issn.2470-5020.jnrt-20-3596
Kombate DamelanCorresponding author University of Kara (Togo)

Background Reversible posterior encephalopathy syndrome (RPE) is a clinical and radiological entity characterized by the acute or subacute fitting of symptoms covering headache, vomiting, visual disturbances, seizures and impairment of consciousness. The pathophysiology of RPE syndrome is poorly described. RPE syndrome is characterized by a reversible cerebral edema of often posterior topography in magnetic resonance imagery (MRI). Cases Presentation We consider RPE syndrome four cases under various conditions that are known as airplane flight, hypertension, non-steroidal anti-inflammatory medication, pregnancy and oldness with several pathologies. The RPE was described with several symptoms like headaches, vomiting, focal motor deficit, paresthesia, seizures, disorders of consciousness and photophobia. The imagery findings were varying from cortical hypersignals in Flair sequences to edema of both cortex and sub cortex. The outcome was good with a complete regression of symptoms and imagery lesions. Conclusion The pathophysiological mechanism of RPE syndrome remains unknown. High blood pressure, renal failure and drugs (anti-depressants, NSAIDs, immunosuppressants) are the most etiological factors. The diagnosis is based on clinical arguments and brain MRI. The main location is posterior. The clinical outcome was good with all the patients in our study, no recurrence was noted.

Energy Conservation Open Access

The Interaction Model of Concentrated Solar Radiation with Materials

Oct 2020 DOI 10.14302/issn.2642-3146.jec-20-3551
M. S. PayzullakhanovCorresponding author

The paper analyzes approaches to modeling the processes of interaction of concentrated solar radiation with materials. The experimental results obtained on the synthesis of materials from a melt in a solar furnace are presented. The features of the interaction of concentrated solar radiation with materials are analyzed. The mechanisms are described and a model for the interaction of concentrated solar radiation with materials is created. A feasibility study is proposed for the technology of glass-based glass materials obtained on the Big Solar Furnace.

SARS-CoV-2 affected cells Pathogeny and Therapy

Sep 2020 DOI 10.14302/issn.2692-1537.ijcv-20-3538
M.R PonizovskiyCorresponding author Kiev, Ukraine, “Kiev regional p/n hospital”, /Head of “Laboratory Biochemistry and Toxicology”

There were compared mechanisms infecting a human organism by different viruses in relation to interaction between human diploid cellular cycle mechanisms and coronaviruses haploid genomic mechanism. Besides there were described mechamism forming combined haploid-diploid cellular cycle of viral affected cells due to interactions between human cellular cycle mechanisms and coronaviruses genomic mechanism. Further there were considered infected way of SARS-CoV-2 from mechanism maintenance stability Internal Energy of an organism’s able-bodies cells and transmutation them into viral affected cells leading to death of affected cells of high respiratory level in nose-trachea-bronchi with transiting coronaviruses through dead cells‘ wall and infecting lungs‘ cells. Taking into account great searches of methods treatments Coronaviruses infected disease, we offered to approved through detail clinical Trial of new efficient method of treatment ill patients with SARS-CoV-2 disease which can rescue of still alive lungs‘ cells. Moreover there was reviewed offered therapy of SARS-CoV-2 induced disease.

Effect of Drought and Salt Stress on Cereal Crop Plants and their Proteomic and Physiological Studies

Sep 2020 DOI 10.14302/issn.2576-6694.jbbs-20-3525
K. Srivastava RajeshCorresponding author Department of Biotechnology, GITAM Institute of Technology, GITAM Deemed to be University, Gandhi Nagar Campus, Rushikonda, Visakhapatnam - 530045 (A.P.), India.

The photosynthetic potential and underlying internal metabolism of a plant are some of the most commonly affected physiological functions as a direct consequence of stresses due to salt and water resulting in hindering plant growth and productivity. Under the influence of such detrimental stresses, a drastic alteration in a plant's osmotic requirements, hormonal production, shedding of leaves, and closure of stomata, along with a lessening in the diffusion and transportation of CO2 and H2O are commonly seen. This review unfolds with a description of the basic methodology involved in the proteomic analysis of various proteins involved in stress response along with a brief idea on identifying and obtaining a genomic sequence for proteomic studies. It then dives deep into understanding the impact of abiotic stresses such as salinity, drought and high temperatures on cereal crops such as rice and sorghum as well as the internal dynamics of tolerance mechanism unfolding during stresses have also been described. Extensive literature describing the proteomic and physiological responses to primary and secondary effects of salt stress in cereal crops emphasizing on ROS production and apoptosis, the role of osmolytes as ROS scavengers during osmotic stress and vacuolar antiporters in ionic stress along with the responses during drought stress such as the accumulation of LEA proteins and ABA-based signaling has been reviewed and critically discussed. The study also sheds light on some experimental proteomic studies conducted on the seedlings, root tissues, and shoots of rice cultivars.

Glandular and Cystic Bladder Cystitis: Case Report and Review of the Literature

Jun 2020 DOI 10.14302/issn.2574-4526.jddd-20-3410
Darouichi M.Corresponding author Institute Medical Champel, 1206, champel, Geneva, Switzerland

Glandular-cystic bladder cystitis is a rare, benign non-tumor condition, preferentially located on the area of the bladder trigone and can simulate a malignant tumor. It is a benign reactive metaplasia of the bladder submucosa, characterized by hyperplasia of the islets of Von Brunn and cystic. It is classified among reactive epithelial anomalies of the urothelium, such as islet hyperplasia of Von Brünn, cystitis, glandular cystitis, nephrogenic metaplasia and epidermoid metaplasia. It presents a clinical diagnostic challenge having the expression of a simple recurrent cystitis and misleading the radiological diagnosis evoking a malignant tumor of the bladder. Its certainty diagnosis is histological. We report the case of a 38-year-old young man who consulted for recurrent cystitis. The CT scan showed a vegetative tissue structure of the middle and left medial vesical floor, sawtooth 3 cm long axis suspecting a tumor of the bladder. The patient underwent transurethral resection of the bladder lesion. The histological and immunohistochemical examination concluded with glandular and cystic cystitis (minor form). In the light of this observation, we will discuss the diagnostic difficulties, the pathophysiological mechanisms, the radiological aspects, the anatomopathological, therapeutic features and the prognosis of this rare condition. The literature regarding this entity has been reviewed and the differential diagnosis was discussed.

Biomedical Infophysical Models of Filtering Ghost Airflows by Wearing Masks and Maintaining Social Distancing to Prevent COVID-19 and Reopen All Systems after Shutdowns (Lockdowns)

Jun 2020 DOI 10.14302/issn.2641-4538.jphi-20-3426
Cheng KangCorresponding author Basic Medicine, Medical School, Qingdao Binhai University, Qingdao, P.R. China

The COVID-19 pandemic has killed more than 400 thousand and infected more than 7 million people in the whole world as of 06/10/2020. Many open systems, such as educations, transportations, entertainments, sports or foods, have been completely or partially locked down in many regions of the world to prevent COVID-19 spreading. Therefore, how to reopen all of the open systems after the shutdown has become a world urgent issue. Evidences of COIVD-19 have showed: person-to-person transmission occurs among close contacts; virus droplets (or aerosols) play an important role in the transmission; people can prevent COVID-19 by measures of mask-wearing or maintaining social distancing. However, how these measures work to prevent COVID-19 is still not clear in a perspective of biomedical Infophysics. In this study, (1) we think the transmission of infection can be accomplished by real or virtual person; (2) we define a virtual person as ghost airflow, a term we coin to describe virus droplets (or aerosols) that are initially generated by human carriers and remain in the air to be transmitted. These ghost airflows are as dangerous as the real virus carriers particularly in enclosed (confined) environments; (3) we propose biomedical infophysical models (BMIPM) of filtering the ghost airflows by mask-wearing and maintaining social distancing, to help people to understand the filtering mechanisms and willingly follow the guidelines of preventing covid-19, and therefore to successfully reopen all of the open systems after the shutdowns (lockdowns) and (or) to avoid the shutdowns (lockdowns) in future epidemics or pandemics. Significantly, we compare the prevention efficiencies of COVID-19 between people who are accustomed and not accustomed to masks based on the published WHO, CDC or NHC pandemic data. The compared results support our models in this investigation. Coronaviruses easily survive and have high toxicity, in dirty, wet and cold environments, and the air pollution is linked with higher COVID-19 death rates. The dingy environments and air-conditioning, freezing systems sufficiently provide such necessary dirty, wet and cold conditions and polluted airflows to exacerbate the mortality rate of COVID-19. Therefore, we strongly suggest: to use air conditioners as less as possible, to turn the wind levels as low as possible and to clean (disinfecting) the air-conditioning systems (filters and channels) and environments as frequent as possible.

Reasons for Increased Social Distancing and Surface Disinfection from a Physics Perspective

Apr 2020 DOI 10.14302/issn.2691-8862.jvat-20-3321
Tang Wen-XinCorresponding author College of materials science and engineering, Chongqing University, Chongqing 400044, China

This viewpoint uses physical principles to explain mechanisms behind social distancing and surface disinfection. It links particle dynamics and contact transfer to practical guidance and risk communication during respiratory epidemics.

Mathematical Modeling and Epidemic Prediction of COVID-19 and its Significance to Epidemic Prevention and Control Measures

Mar 2020 DOI 10.14302/issn.2766-8681.jcsr-21-3719
Zhao BinCorresponding author School of Science, Hubei University of Technology, Wuhan, Hubei, China.

Background Since receiving unexplained pneumonia patients at the Jinyintan Hospital in Wuhan, China in December 2019, the new coronavirus (COVID-19) has rapidly spread in Wuhan, China and spread to the entire China and some neighboring countries. We establish the dynamics model of infectious diseases and time series model to predict the trend and short-term prediction of the transmission of COVID-19, which will be conducive to the intervention and prevention of COVID-19 by departments at all levels in mainland China and buy more time for clinical trials. Methods Based on the transmission mechanism of COVID-19 in the population and the implemented prevention and control measures, we establish the dynamic models of the six chambers, and establish the time series models based on different mathematical formulas according to the variation law of the original data. Findings The results based on time series analysis and kinetic model analysis show that the cumulative diagnosis of pneumonia of COVID-19 in mainland China can reach 36,343 after one week (February 8, 2020), and the number of basic regenerations can reach 4.01. The cumulative number of confirmed diagnoses will reach a peak of 87,701 on March 15, 2020; the number of basic regenerations in Wuhan will reach 4.3, and the cumulative number of confirmed cases in Wuhan will reach peak at 76,982 on March 20. Whether in Mainland China or Wuhan, both the infection rate and the basic regeneration number of COVID-19 continue to decline, and the results of the sensitivity analysis show that the time it takes for a suspected population to be diagnosed as a confirmed population can have a significant impact on the peak size and duration of the cumulative number of diagnoses. Increased mortality leads to additional cases of pneumonia, while increased cure rates are not sensitive to the cumulative number of confirmed cases. Interpretation Chinese governments at various levels have intervened in many ways to control the epidemic. According to the results of the model analysis, we believe that the emergency intervention measures adopted in the early stage of the epidemic, such as blocking Wuhan, restricting the flow of people in Hubei province, and increasing the support to Wuhan, had a crucial restraining effect on the original spread of the epidemic. It is a very effective prevention and treatment method to continue to increase investment in various medical resources to ensure that suspected patients can be diagnosed and treated in a timely manner. Based on the results of the sensitivity analysis, we believe that enhanced treatment of the bodies of deceased patients can be effective in ensuring that the bodies themselves and the process do not result in additional viral infections, and once the pneumonia patients with the COVID-19 are cured, the antibodies left in their bodies may prevent them from reinfection COVID-19 for a longer period of time.

Antioxidant Activity Open Access

Comparative Analysis of Atherosclerosis Risk Factors in the Staff of the Tbilisi (Georgia) Cleaning Service

Mar 2020 DOI 10.14302/issn.2471-2140.jaa-20-3236
Sanikidze TamarCorresponding author Tbilisi State Medical University, Tbilisi, Georgia

Objective Search of pathogenetic mechanisms and risk factors of atherosclerosis in the employees of the cleaning service in Tbilisi. Materials and Methods As a result of a preliminary survey and examination of 200 employes of Tbilisi cleaning service aged 25-45 years (2014-2016), 22 patients with angina, hypercholesterolemia, intimae-media thickness > 0.65 mm, were selected into I group, and 23 individuals without these disorders into II group. In the blood plasma of the selected patients the intensity of oxidative metabolism parameters, TAA and MDA were determined. The variance and correlation analysis (АNOVA) was used for conducting the comparative analysis of the levels of studied parameters. Results In the combined group (I+II) there are several reliable correlations between the Age -TCol, Age-MDA, BMI-Tg, BMI-MDA, LDLChol-HDLChol, LDLChol–TChol, HDLChol-TChol, LDLChol-MDA, LDLChol-TAA. no correlation between these parameters in individual groups (I and II) was found. That indicates that we have an imaginary correlation related to the large intergroup difference between the average values of the group indicators, that is the values of various indicators change during the development of the pathological process, but there is no causal relationship between these alterations. The reliable TAA-MDA correlation in the combined group (I+II) is related to the high anticorrelation between these parameters and the significantly higher average value of TAA in the low-risk group (II) in comparison to the high-risk group (I). Conclusion The results analysis indicates both the diagnostic value of redox status indicators and their leading role in the atherogenesis processes. In populations with a high risk of atherosclerosis, monitoring of serum TAA is recommended.

RETRACTED: Amino Acid Imbalance in Atherosclerosis

Feb 2020 DOI 10.14302/issn.2379-7835.ijn-20-3188
Nefyodov L.I.Corresponding author Department of Biochemistry Yanka Kupala Grodno State University, Belarus

This article has been retracted on 18 March 2021. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2379-7835.ijn-25-5865) A mini-review of literature data on the mechanisms of formation of the stock of free amino acids and their derivatives in atherosclerosis and methods for correcting metabolic imbalance.

Open or Closed?

Jan 2020
Freeman DylanCorresponding author Medical University of South Carolina Storm Eye Institute

A brief educational piece clarifies open‑angle versus angle‑closure glaucoma mechanisms, risk factors, and screening considerations. It provides practical pointers for early detection and referral.

Nephrology Advances Open Access

Evaluation of the Relationship Between Advanced Oxidation end Products and Inflammatory Markers in Maintenance Hemodialysis Patients

Dec 2019 DOI 10.14302/issn.2574-4488.jna-19-3112
Aydin ZekiCorresponding author Darica Farabi Training and Research Hospital, Department of Nephrology, Kocaeli, Turkey

Introduction Increased oxidative stress and blunted anti-oxidant mechanisms are important problems in hemodialysis (HD) patients. Reactive oxygen species (ROS) act directly on proteins, leading to the formation of oxidized amino acids. Advanced oxidation protein products (AOPP) are among these substances. Many oxidant substances increase the level of AOPP. Iron is an element with strong oxidant capacity, especially when used intravenously. It is thought that iron treatment further increases the oxidative stress in HD patients. We aimed to investigate the relationship between AOPP and inflammatory status in HD patients. Materials and Methods Patients who were on maintenance HD program without additional co-morbidities and no history of use of intravenous iron within the last two weeks were recruited in the study. The blood samples taken just before the dialysis session were analyzed for AOPP, serum iron, total iron binding capacity (TIBC), ferritin, C-reactive protein (CRP), ß2-microglobulin, fibrinogen, interleukin (IL)-1, IL-6 and tumor necrosis factor-α levels besides routine biochemical measurements and complete blood count. Results The number of patients included in the study was 102 (n: 53 female, %52.0) and the mean age was 47.6±13.9 years. The mean transferrin saturation was 25.4%. AOPP levels, iron use in patients was higher compared to patients who do not use (respectively 2.58±0.19 mmol/l and 2.50 ±0.16mmol/l, p = 0.046). We did not detect statistically significant correlation of AOPP levels with iron parameters and other inflammatory markers. Conclusion The present study showed that intravenous iron therapy does not increase oxidative stress. Although serum AOPP level was higher in patients on intravenous iron treatment, it was not correlated with iron indices and inflammatory markers. So, intravenous iron may exert its oxidant effect free from serum iron indices.

Agronomy Research Open Access

Sunspots are Correlated with Foliar pH in Grapevines

Dec 2019 DOI 10.14302/issn.2639-3166.jar-19-3116
Masoero GiorgioCorresponding author Accademia di Agricoltura di Torino, Italy

Foliar pH is a specific multifaceted parameter that is sensitive to a deficit in soil water and to temperature variations. It also represents a tool that can be used to rapidly phenotype the symbiosis induced in several crops by bio-fertilizers containing Arbuscular Mycorrhizal Fungi. Yearly decreases in foliar pH, which dropped from 3.73 in 2015 to 3.15 in 2017 and then stabilized at around 3.13, have been observed in an experimental vineyard near Torino (Italy) in six grapevine cultivars. In this paper, these curious, original results have been paired with the average sunspots of the 24th sun cycle, proximal to its endpoint. The paired values were highly correlated (r 0.95 P< 0.01), with close parabolic patterns. A lowering in foliar pH has been correlated with a modification of the leaf composition, as characterized by the higher hydration and reinforced wall. An increase in the circulating acidity of the plants has been hypothesized to interfere in a diminution in the general predisposition to block parasite attacks. From this perspective, the retrieval of several historic outbreaks and the long-term systematic monitoring of mud and Erwinia amylovora frequencies have suggested that the hypothesis that links the solar minima with dysfunctions of the plant-pest relationships cannot always be rejected. Cosmic influences pertaining to UV variations are poorly understood in plant physiopathology. Foliar pH appears to be a rapid and simple tool to unveil high-level mechanisms. It is this simple parameter that physiologists and geneticists, but also agronomists, are asked to consider.

Dispositional Mindfulness, Perceived Stress, and Mental Well-Being in the Cancer Survivorship

Nov 2019 DOI 10.14302/issn.2574-612X.ijpr-19-3093
Zhang JingjingCorresponding author School of Psychology, Nanjing Normal University, Nanjing, China

The present study aims to investigate how dispositional mindfulness affects the mental well-being of cancer patients through the way they perceive stress. A total of 182 moderate and advanced gastrointestinal cancer patients volunteered to complete the Mindful Attention Awareness Scale (MAAS), the Chinese Perceived Stress Scale (CPSS), and the General Health Questionnaire (GHQ). Results showed that perceived stress significantly mediated the relationship between dispositional mindfulness and all dimensions of the mental well-being as captured by the GHQ (i.e. anxiety/depression, social dysfunction, and loss of confidence), and perceived stress was positively correlated with all the dimensions of mental well-being. Results of the Structural Equation Model showed that the model fit the data very well (χ2/df = 1.72,RMSEA = 0.063 (95% CI = 0.014 ~ 0.103), CFI = 0.984, TLI = 0.970, SRMR=0.041). Further analyses showed that dispositional mindfulness predicted all the dimensions of psychological well-being. Specifically, higher levels of dispositional mindfulness predicted reduced subjective perceptions of stress, which in turn predicted lower levels of anxiety/depression, social impairment, and loss of confidence. This study indicated a possible mechanism of intervention focused on improving mindfulness capability. Future work is encouraged to investigate the long-term influence of dispositional mindfulness on perceived stress and psychological well-being in cancer patients with other types of cancer.

Capsaicin: A Potential Therapy Adjuvant for Intestinal Bowel Disease

Nov 2019 DOI 10.14302/issn.2574-4526.jddd-19-3063
I Alvarez-Leite JacquelineCorresponding author Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerias, Brazil.

Most of the patients with inflammatory bowel disease avoid pepper or spicy food, alleging that this condiment causes anal sensation of burning and accelerates intestinal movements. Capsaicin is the main bioactive component of peppers responsible for the pungent flavor that characterizes red peppers. Capsaicin has been related to several biological effects, including decreased body fat, antianti-inflammatory, anticarcinogenic, antioxidant activites and modulator of intestinal motility. These actions mostly are due to its role as an agonist of the transient receptor potential vanilloid 1 (TRPV1), expressed in the mesenteric nervous system and epithelial cells of the colon. Nonetheless, the anti-inflammatory action of capsaicin is also related to its role in activating the peroxisomal proliferator-activated receptor gamma (PPAR-γ). Topical capsaicin formulations are already used for pain management, but oral administration of capsaicin is rare. Here, we discuss the main actions of capsaicin that could interfere with the symptoms and severity of IBD. Although animal experiments suggest a beneficial effect of capsaicin on colitis, clinical studies exploring the potential analgesic and anti-inflammatory of capsaicin on Crohn or Ulcerative Colitis are scarce. We concluded that there is no evidence that capsaicin aggravates IBD symptoms or severity. On the opposite, experimental studies suggest that capsaicin could reduce intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPAR γ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.

Triacontanol Alleviated Nickel Toxicity in Maize Seedling by Controlling Its Uptake and Enhancing Antioxidant System

Oct 2019 DOI 10.14302/issn.2638-4469.japb-19-3051
Ahmed Ismail HebatollahCorresponding author Botany Department, Faculty of Science, Ain Shams University, Cairo, Egypt

Triacontanol (TRIA) role in improving growth, physiological activities and tolerance against abiotic stresses has been reported. Yet, the mechanism by which TRIA executes its effects remains elusive. This work therefore studied the possible role of TRIA exogenous application in counteracting the adverse effects of nickel (Ni) treated maize seedlings. Maize seedlings (15-day-old) were grown in washed sand irrigated with nutrient solution provided with 100 μM NiCl2. Two concentrations of TRIA (25 and 50 µM) were applied twice as a foliar spray for Ni-stressed seedlings. Shoot and root growth attributes, Ni content, and antioxidant defence systems of maize seedlings were determined. Ni treatment reduced the shoot and root length and biomass, causing necrosis of the old leaves,greater reduction was shown in the roots. The shoot and root length was negatively correlated with their Ni content, which was consistent with their content of H2O2, but not with their malondialdehyde (MDA) content. As the roots had the greatest Ni content, maximum peroxidase (PX) and glutathione reductase (GR) activity as well as the highest ascorbic acid (ASA) and reduced glutathione (GSH) content were observed in the roots. The Ni-induced deleterious effects were alleviated by foliar application of TRIA concentrations. Also, TRIA treatment minimized root Ni content, whereas it maintained the shoots unharmed by Ni. Such mitigative effects of TRIA are explained by its key role in enhancing antioxidant capacity (expressed as IC50), increased PX and ascorbate oxidase (AO) activity, GSH, and total phenolic contents.

Assessment of Anticancer Effect of Alendronate in Breast Cancer: An In vitro Study

Aug 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2953
Syed Amber Ilyas NidaCorresponding author National Center for Proteomics, University of Karachi, Karachi 75270, Pakistan

Breast cancer has high incidence in women from both developed and developing countries. Approximately 2 million women are diagnosed with breast cancer in 2018. In Asia, unfortunately Pakistan leads the highest number of breast cancer patients. Various treatment strategies are present but they are not well developed. There is a great need to develop effective methods for early detection and treatment of the disease. For cancer treatment chemotherapeutic interventions have always been a method of choice. One of the mechanisms involved in cancerous cell proliferation is Mevalonate (MVA) pathway. It is hypothesized that arresting MVA pathway leads to cell death hence cancer cell growth is suppressed. Various inhibitors of MVA pathway have been studied that can suppress cell proliferation. Nitrogen containing bisphosphonates are MVA pathway inhibitor and clinically used for treatment of bone diseases. Their anticancer efficacy is also reported. Current study focuses on alendronate, a nitrogen containing bisphosphonate to examine their anticancer effect on breast cancer cell line. Results of this study may help in addition of new anticancer drug for breast cancer.

A Triple-Blind, Placebo-Controlled Randomized Trial of the Effect of Bilateral Alternating Somatosensory Stimulation on Reducing Stress-Related Cortisol and Anxiety During and After the Trier Social Stress Test

Jun 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2784
Cesar Pinto Leal-Junior ErnestoCorresponding author Laboratory of Phototherapy and Innovative Technologies in Health, Nove de Julho University – UNINOVE, Sao Paulo, Brazil.

The aim of this clinical study was to determine the efficacy of bilateral alternating somatosensory stimulation for the management of stress and anxiety during and after the Trier Social Stress Test (TSST), a laboratory procedure for reliably inducing stress in human subjects. For this, a randomized, placebo-controlled, triple-blinded clinical trial of 80 qualified subjects was conducted. Subjects were randomized into two groups, a treatment group (n=40) and a control (placebo) group (n=40). Metrics of emotional stress assessed were a subjective rating of the level of emotional stress and salivary cortisol levels, both obtained at 3 timepoints: before treatment (baseline), immediately following completion of the TSST, and after 20 minutes of rest following completion of the TSST. Results showed that the treatment group had a statistically greater decrease in the subjective rating of stress relative to the control group both immediately following the TSST and 20 minutes after the TSST. Salivary cortisol levels in the treatment group were also lower than the control group at those same time points. These results suggest that bilateral alternating somatosensory stimulation may be effective in reducing subjective levels of stress and anxiety. It also may actively attenuate stress-related cortisol levels, which may reflect a mechanism for reducing cortisol-induced inflammation back to baseline after exposure to stressful situations.

Outcome Assessment of Open Foot Injuries in A Teaching Hospital in Ghana

Jun 2019 DOI 10.14302/issn.2474-3585.jpmc-19-2750
Konadu-Yeboah DominicCorresponding author Orthopaedic and Trauma Surgeon, Komfo Anokye Teaching Hospital, Kumasi, Ghana, Part-Time Lecturer, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

Purpose Foot injuries are common in low- and middle-income countries and continue to increase in incidence due to the surge in the use of motorcycles as means of transport.Yet, there is scanty data on the incidence and outcomes of treatment of open injuries to the foot in the developing world.We aimed to determine the incidence and functional outcomes of open foot injuries that are treated in a teaching hospital in Ghana. Methods We used a structured questionnaire to record the type of open foot injury, the mechanism of injury, any concomitant injuries, the time interval between injury and arrival at the hospital for treatment as well as the type of treatment instituted. Recruited patients were followed up for six months, complications resulting from the injury or its treatment were recorded for each patient. The function of the foot after healing of the injury was measured using a questionnaire-based visual analogue outcome scale of the American Foot and Ankle Society. Regression and chi-square analysis were used to evaluate potential associations. Results Over a four-month period, a total of 81 cases of open injuries to the foot were recorded. Out of this figure, 55 patients (67.9%) were males and 26 (32.1%) were females. It was found, that 66.7% aged between 19 and 49 years, 76.5% of the injuries occurred on the road and 29.7% was motor cycle related. Pedestrians are the most afflicted (61.7%). The treatment outcomes of traumatic amputations, open phalangeal fractures, dorsal skin degloving and lacerations were good. Gustillo-Anderson grade IIIB open fractures with associated plantar skin degloving had the worst outcomes with residual pain on weight bearing, bigger foot, inability to wear previous shoes and inability to tiptoe on the affected foot. Conclusions Open injuries to the foot are common in Ghana and exert a significant health burden, particularly on active young males. Long term disability may occur, even after adequate treatment of open fractures involving the foot.

Research Status and Application Prospect of Epigenetic Regulation of BDNF Gene Expression in Chronic Pain 

Jun 2019 DOI 10.14302/issn.2688-5328.ijp-19-2731
Wei XiangCorresponding author Hospital of Suzhou University, Suzhou, China

The rise of epigenetics provides a new idea for studying the regulation of chronic pain-related genes and synaptic plasticity. External environmental stimuli can regulate BDNF genes through different epigenetic modifications. The epigenetic changes of the BDNF gene can affect the expression of its mRNA and protein and participate in the development of chronic pain. By reviewing the literature, this paper reviews the mechanism of epigenetic regulation of brain-derived neurotrophic factor (BDNF) in chronic pain, which provides some new directions and targets for the treatment of chronic pain.

Cardiac Inflammatory Pseudotumors in Behçet’s Disease

May 2019 DOI 10.14302/issn.2329-9487.jhc-19-2787
Bouomrani SalemCorresponding author Department of Internal medicine. Military Hospital of Gabes. Gabes 6000. Tunisia

Introduction Cardiac non-specific inflammatory pseudotumors (NSIPT) are exceptionally associated to Behçet's disease (BD) and represent a real diagnostic and therapeutic challenge. The meaning and the mechanisms of this association are not yet well understood. The purpose of this paper is to study the epidemiologic, therapeutic, and evolutionary characteristics of cardiac NSIPT during BD Methods Systemic review of all reported cases of cardiac NSIPT associated with BD. Results We found only 6 cases of NSIPT associated with BD. Of these six patients, 4 were men (66.66%) and 2 were women (33.33%): Sex ratio =2. The average age was 26.66 years (9-35 years). The pseudotumor was unique in all cases. The chronology of occurrence of these NSIPT compared to the underlying angiitis was variable: inaugural of the disease in 4 cases, and complicating a previously known BD in 2 cases. The surgery was performed in all cases. It was carried out for diagnostic purpose in 4 cases, and therapeutic in the other 2. Additional medical treatment based on systemic corticosteroids with or without immunosuppressants was indicated in 4 patients. The evolution was favorable in 5 cases and a single case was quickly fatal. Recurrence of NSIPT was reported in one patient (20%). Conclusion The results of this review suggest a very likely association between BD and cardiac NSIPT; especially because of the scarcity of these two conditions in the general population, and the epidemiological characteristics clearly different from those of cardiac NSIPTs in the general population. The pathogenic mechanisms common to these two conditions (immune, inflammatory, reactive, and vascular) reinforce this causal link. The main differential diagnoses of these pseudotumors during BD remain cancer and intracardiac thrombosis.

Concomitant in Vivo Voltammetric and Electrophysiological Analysis Indicate that Nociceptin/Orphanin FQ Affects Dopamine and then Serotonin Activities in Brain Substancia Nigra.

Apr 2019 DOI 10.14302/issn.2578-8590.ipj-19-2772
Crespi FrancescoCorresponding author Biology, CSK, Verona, Italy

Nociceptin/orphanin-FQ (NOCI) together with its receptor NOP are widely expressed in cortical and subcortical motor areas and it is known that NOCI acts as an anxiolytic attenuating the behavioral inhibition of animals acutely exposed to stressful/anxiogenic conditions. Influence of NOCI upon the dopaminergic system has been observed in the ventral tegmental area and in the nucleus accumbens as well as an inhibitory action of NOCI is described upon serotoninergic mechanisms at cells and terminal levels. In particular, it is known that serotoninergic fibers from the raphe system project to the substancia nigra (SN) and that this modulation is behaviourally relevant. In the present work, the effect of exogenous NOCI injected into the SN upon DA and 5-HT levels have been analyzed by means of differential pulse voltammetry and nafion-carbon fiber microelectrodes. Electrophysiological monitoring of multicell activity was concomitantly performed with the same microsensor. It appeared that both levels of these biogenic amines were specularly altered, with possibly a driving influence of the DA activity upon the serotoninergic function(s).

Adrenomedullin as a Protein with Multifunctional Behavior and Effects in Various Organs and Tissues

Apr 2019 DOI 10.14302/issn.2641-9181.ijnr-19-2771
Ozcelik FatihCorresponding author University of Health Sciences, Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Turkey

In literature, it has been reported that adrenomedullin, which is generally thought to have vasodilator, natriuretic and diuretic effects, is synthesized in almost all body, especially CNS, vascular muscles and endothelium, heart, liver, lung, kidney, gastric mocosa, intestinal endothelium and various blood cells. It has been found that the possible effects of adrenomedullin can be demonstrated directly or indirectly by means of active mediators, neuropeptides, enzymes and hormones. It is also suggested that it regulates the endocrine system by affecting the hypothalamic-pituitary axis. It increases in heart failure, acute coronary syndromes, hypertensive conditions, cerebrovascular accessory, chronic renal failure and periodontitis and decreases in peptic ulcer and intestinal diseases. However, it is still not clear whether increase/decrease in adrenomedullin level is a cause of a disease or is a result of damage due to an illness. This peptide, which could be thought to multifunctional, should be considered as a molecule with genetic coding that may have different effects on different tissues and conditions. For all these reasons, we aimed to review the multifonctional behavior of adrenemedullin in the light of the current literature to pioneer new hypotheses and discuss possible mechanisms.

Family Medicine Open Access

Exploring the Experiences of Partners of Veterans with Mental health Difficulties Attending a Group Psychoeducation Support Intervention: A Qualitative Study.

Mar 2019 DOI 10.14302/issn.2640-690X.jfm-19-2726
Spencer-Harper LucyCorresponding author Combat Stress, Leatherhead, UK.

Background Research has demonstrated that partners living alongside veterans with mental health difficulties are at high risk of developing mental health difficulties themselves and secondary trauma. A variety of interventions have been developed to support partners. Research to date has relied on quantitative methodologies to evaluate the efficacy of such interventions with less emphasis on learning about the experiences of individuals on the courses. Objective The aim of this qualitative paper was to understand the experiences of partners who engaged in a five-week structured support intervention, ‘The Together Programme’ (TTP) which had been piloted across UK cities. This programme involved tailored psycho educational materials adapted to the needs of veteran’s partners living alongside PTSD. Further the potential mechanisms of change for participants engaged with the programme were explored as well as the impact of treatment on their relationships. Methods Eight female partners were recruited from an original sample of 57 partners who were intimate relationships with treatment seeking veterans with mental health difficulties. These participants had completed TTP. Qualitative data was collected using a semi structured interview and explored using Interpretative Phenomenological Analysis. Results Three key themes emerged from the data, these were self-growth, changing role in relationships and connecting with others. The themes included several sub themes. Self-growth sub-themes were mastering the ‘inner judge’, ‘confidence in ability to cope’ and ‘taking care of my needs’. Changing role in relationship sub-themes were ‘acceptance and understanding’ and ‘improved communication in relationship’. Connecting with others was described by the sub-themes of ‘knowing I am not alone’, ‘peer support’ and ‘hope’. Conclusions This study suggeststhere were three key areas where thestructured evidence-based support programme had an impact on participants experiences. These were factors that helped participants to normalise their experiences and increase participants understanding and interpersonal skills that promote changes in relationship functioning with the veteran.

Yeast Species Mediated Bioprocesses and Bio-Products for Biotechnological Application

Mar 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2684
K. Srivastava RajeshCorresponding author Department of Biotechnology, GIT, GITAM (Deemed to be University), Rushikonda, Visakhapatnam-530045 (A.P.), India.

Yeast as unicellular organism, has shown multiple application due to exhibition of noble ability in its cells. And engineered yeast has found more suitability in bioprocesses application as well as adverse conditions adaptation. Different types of yeast strains showed their best capability to adapt the salt and sugar rich environment with their optimal growth capability. These strains, used as suitable and novel cell factories for production of value added bio-products (via utilization of fermentation processes) and also for different types of bioprocesses. Application of yeast species in biotechnology field, enhanced in current periods, due to conversion of its wild to engineer strain, suitable for bioprocesses utilization and also for different types of biochemical synthesis. Different yeast species identified due to known their genetic, regulatory mechanism and also competitive metabolic pathways. In this regards, different type of engineering approaches (for genetic or pathways modification), applied to construct the optimal and suitable cell factories for different types of bioprocesses as utilized in different sectors (foods with mineral or protein rich, bread, brewing, cosmetics, chemical, agriculture, pharmacy and distillation industries) via improving the quality of bio-products. Further, in silico designed based metabolic engineering technique showed the improvement in performance of yeast strain. System and synthetic biology with engineering approaches applied to further improve the yeast mediated bioprocesses as well as biochemical products formation for industrial or biotechnological application. Some bio-products such as functional bio-molecule, different types of alcoholic biofuels, organic acids and enzymes etc are good examples of yeast mediated biochemicals products, utilized more frequently in our life. Author will focus recent research and development on bio-product formation or bioprocesses with their regulatory control mechanism in different yeast strains.

Developing Cellular & Molecular Biomarkers for Anti-Inflammatory Activities of Probiotic Bacteria in Fermented Foods

Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2578
E. Ahmed FaridCorresponding author GEM Tox Labs, Institute for Research in Biotechnology, 2905 South Memorial Drive, Greenville, NC 27834, USA.

We present below a mechanistic cellular and molecular approaches for the development of Anti-Inflammatory biomarkersof Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses approaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory pathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary components on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.

Brain Hemodynamics and Cerebrovascular Reactivity in Patients with Tension-Type Headache

Jan 2019 DOI 10.14302/issn.2470-5020.jnrt-18-2555
Ya. Abdullaiev RizvanCorresponding author Kharkiv Medical Academy of Postgraduate Education, Department of Ultrasound Diagnostics, Ukraine

Introduction: Tension-type headache (TTH) is very common, with a lifetime prevalence in the general population ranging in different studies between 30% and 78%. TTH, divided into episodic and chronic types, introduced in the manual "International Classification of Headache Disorders"(ICHD-I), is of practical importance. Infrequent episodic headaches (no more than once a month) may not require drug therapy, but, on the contrary, frequent forms may require expensive treatment. Objective: To study the state of cerebral hemodynamics and cerebrovascular reactivity in patients with Tension-type headache and evaluate the efficacy of treatment with Phenibite using Doppler ultrasound. Materials and Methods: A retrospective analysis of the results of ultrasound dopplerography of the anterior, middle and posterior cerebral arteries (ACA, MCA and PCA), Vertebral and Basal (VA, BA) arteries was performed in 188 patients with TTH. Among them are infrequent episodic TTH - 68 (36,2%) patients, frequent episodic TTH - 64 (34,0%) patients, chronic TTH - 56 (29,8%) patients. The age of the subjects was 18-45 years, among them 85 (45.2%) men and 103 (54.8%) women. The maximum systolic velocity (Vs), the end diastolic velocity (Vd), the resistance and pulsativity indexes (RI, PI) in all vessels were determined. Patients were given consent to participate in the study. Results: Infrequent episodic (IFE) TTH were recorded in 86.4% of cases, frequent episodic (FE) — in 88.9%, and chronic (Ch) TTH — in 81.6% of cases. Bilateral TTH was noted in 39.2%, frontal localization - in 35.6%, in the occipital region - in 25–7% of cases. The asymmetry of the maximum systolic blood flow velocity (Vs) in the paired arteries within 20-30% was considered a violation of cerebral hemodynamics, which was detected in 38.7% of patients. An increase in Vs was noted in all cerebral vessels, especially in patients with FE TTH and chronic Ch TTH compared with the control group. In patients with IFE TTH the average value of RcFMt was 1.24±0.03, in patients with FE TTH - 1.25±0.02, in patients with Ch TTH - 1.27±0.03. In patients with TTH, hyper-responsiveness to hypercapnic test was detected: RcCO2 was 1.43±0.05 in the group with FE TTH; 1.39±0.07 in the group of Ch TTH and 1.37±0.04 in the group of IFE TTH, which indicates a tendency for the tension of the vasodilator regulation mechanism even in clinically insignificant forms of TTH. In the study of reactivity to the O2-test, a hyporeactive response was observed in the groups with FE TTH and Ch TTH (0.38±0.04 and 0.35±0.05, respectively. The treatment with Phenibut carried out in a step-by-step manner - during the first week the drug was applied at a dose of 250 mg 2 times a day, over the next 6 weeks the dose increased to 500 mg 2 times a day, then the dose was reduced back to 250 mg 2 times a day. Among patients with FE TTH, the frequency of headache decreased from 5.7±2.3 to 3.6±2.1 days/month, and in patients with Ch TTH - from 22.8±1.7 to 17.7±1,3 days/month (P<0,05). Influence of the drug was manifested at the initially increased RcFMt and RcCO2. A decrease in initially elevated RcCO2 was noted in all (FE TTH, ChTTH, IFETTH) clinical groups. However, this decrease was not statistically significant. Conclusion: In patients with TTH, an increase in the Vs is more often recorded, their asymmetry in the middle cerebral artery. Hyperreactivity on CO2-load is typical for patients with chronic TTH, and reflects the mobilization of metabolic regulation of cerebral blood flow. Conducting FMt was the most informative method for detecting autoregulatory disorders mainly in patients with IFE TTH. FE TTH in patients is characterized by the presence of a hyperactive reaction to hypercapnic and orthostatic tests, probably due to mobilization of humoral-metabolic and neurogenic links of regulation. In the group of patients with chronic TTH prevails hyporeactivity for hyperventilation test, reflecting the depletion of vasoconstriction reserve. The use of Phenibut(Noophen® (JSC Olainfarm Latvia in the treatment of TTH is accompanied by a decrease in the frequency of pain, and of pericranial muscle tone, most pronounced in patients with FE TTH. It's effectiveness is evident in the normalization of the coefficients of cerebrovascular reactivity in a patients with chronic TTH. The minimal statistical significance was observed on the dynamics of blood flow only in the VA.

Adaptive Contribution of Thyroid Hormones in Obesity

Jan 2019 DOI 10.14302/issn.2641-9181.ijnr-18-2530
Ozcelik FatihCorresponding author University of Health Sciences, Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Turkey

Nowadays, obesity is seriously threatening healthy life in all societies, especially in developed societies. Obesity is showing its likely effects through biologically active substances called adipokines. The most familiar of these is leptin. Leptin is synthesized in directly proportional to the amount of adipose tissue and reduced appetite by stimulating the satiety center. This status is like a protective mechanism that tries to reverse severe pathological process. Similar to this behavior of leptin, thyroid hormones are increasing in the advanced stages of obesity, increasing the resting energy expenditure (REE). The accelerating oxidative phosphorylation causes the use of energy as heat, the energy that has not transformed into ATP, together with ATP synthesis. This situation, the significant portion of energy provides to consumed instead of storing as fat. In addition, finding that T3 accelerates glucose transport and the TCA cycle without changing the rate of ATP synthesis in skeletal muscles suggests that thyroid hormones may be an effective tool in standing against obesity. In addition of that, the presence of studies indicating that thyroid hormones have an increasing tendency in the advanced stages of obesity is likely thought to be a rescuer mechanism to increase the effectiveness of suppressed thyroid hormones. On the contrary of these ideas, having been reported suppressing 5’-deiodinease enzyme activity in chronic diseases causes anxiety about the effectiveness of thyroid hormones in obesity. Based on available information, we aimed to prepare a review evaluating of this adaptive condition of thyroid hormones.

The Current Immunoassays and Emerging Immunogenomic Approaches for Immunomonitoring Cancer and Infectious Diseases

Jan 2019 DOI 10.14302/issn.2572-3030.jcgb-18-2527
Zhang XiCorresponding author Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, United States

As remarkable advances have been made in immunotherapies, the overall goal of immunotherapy has become the selection of patients and evaluating the benefits of treatment. One of the major obstacles to develop immunotherapies is the lack of effective immune monitoring. Monitoring of key changes in the immune system during immunotherapy (immunomonitoring) provides important insights into efficacy as well as the immune mechanisms of response at the molecular and cellular levels. Immunomonitoring techniques include traditional immunoassays that use specific antibodies to recognize the analytes of interest, new high-throughput immunoassays that target immune cells and nucleic acids, and less classical immunogenomic approaches that rely on genome-wide profiling and computational analysis on various types of clinical samples. Substantial progress has been made in the application of immunomonitoring strategies to pre-clinical and clinical studies, especially for patients with cancer and infectious diseases. Current and emerging immunoassays performed in clinical practice will be examined herein, and immunogenomic approaches that complement these techniques will be highlighted and compared with traditional methods. Finally, we will discuss several new computational methods for analyzing gene signatures for immunomonitoring, including gene expression data profiling by microarray, the nCounter technique, regular RNA-seq, and single-cell RNA-seq. Novel immunomonitoring techniques, especially immunogenomic approaches, will continue to be developed to facilitate assessment of immunotherapeutic response and predict patient outcomes in cancer and infectious disease.  

Epigenetic Biomarkers in Head and Neck Cancer 

Nov 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2428
Gupta ShilpiCorresponding author Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida-201313, India.

Head and neck cancers (HNCs) are the most prevalent and aggressive type of cancers. Genetic, epigenetic, environmental and viral risk-factors are associated with HNC carcinogenesis. Persistent infection of oncogenic human papillomaviruses (HR-HPVs) represent distinct biological, molecular and epigenetic entities in HNCs. There are three main epigenetic mechanisms that regulate transcription, these are DNA methylation, histone modifications and alteration in non-coding RNA networks, which can dissected to identify innovative and accurate epigenetic biomarkers for diagnosis and prognosis of HNC patients. Due to the lacunae of accurate distinctive biomarkers for the definite diagnosis of HNC, the identification of predictive epigenetic markers is necessary that might modify or increase HNC patient’s survival. In this mini review, we briefly summarize the current knowledge of different epigenetic biomarkers in HNC.

Veterinary Healthcare Open Access

Hepatic Metabolomics Profiling of Cyprinus Carpio after Acute Cypermethrin Toxicity

Nov 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2455
Habotta OlaCorresponding author Education and Research Center for Marine Resources and Environment, Faculty of Fisheries, Kagoshima University, Japan.

In the current study, The GC-MS metabolomics approach was used to evaluate the effect of cypermethrin on the metabolic profile in liver tissue of common carp fish. Fish were exposed to low and high concentrations of cypermethrin (0.1 and 1 µg/L respectively) for 24 and 96 h with subsequent PCA analysis to illustrate the response of the metabolic system after exposure to the pyrethroid. Cypermethrin induced obvious alteration in the intermediates of TCA cycle and encouraged consumption of non-carbohydrate sources in liver at all-time points. Additionally, cypermethrin exposure reduced the level of several amino acids and induced damage to the nucleotides reflecting the effect of cypermethrin on purine metabolism. GC-MS based metabolomics approach is a new and powerful tool to understand the toxicological effects and the underlying mechanism of cypermethrin on fish.

Agronomy Research Open Access

The Raw pH in Plants: A Multifaceted Parameter

Oct 2018 DOI 10.14302/issn.2639-3166.jar-18-2397
Masoero GiorgioCorresponding author Accademia di Agricoltura di Torino, Torino, Italy

The measurement of the in vivo raw pH of vegetative organs is a unusual way obtaining plant knowledge. The authenticity of the pH parameter of the leaf and its independence from soil pH has already been highlighted. In the present work we observe how and to what extent water-temperature mechanisms as well as bio-fertilizers inocula can affect the raw pH and how great the biodiversity is in plants. A trial with Arabidopsis thaliana in a phytotrone has shown that, in the dark, the raw pH did not change from +18 to +35 °C (b = -0.0027 N.S.), while in the light, the regression coefficients were significant and negative, and the acidification in the leaves progressed from high (-0.0097) to normal (-0.0127) and then to low (-0.0370) water level. We have confirmed that warming induces a decrease of raw petiole pH of -0.070 pH C°-1 in grapevine leaves. In accordance with water-temperature mechanisms, the raw pH in grapevines has been found to be significantly higher in well-watered plants (pH = 4.29) than in stressed ones (4.12), with a pH decay of -3.9%. On the other hand, an average reduction of 0.10 units of raw pH would signal an increase in water stress of about -0.59 Mpa. Among the phenomena that can influence the raw pH, we have outlined three biotic factors: i) acidification as a result of a symbiotic farming fertilization i.e through the use of mycorrhizal and microbial fertilizers, with an average decay of around -3%, as a probable signature of symbiosis; ii) an “acida plantarum natura” scenario over 49 species, ranging from pH 3.06 to 6.38 ; iii) a strong (R2= 0.9) inverse polynomial pseudo-relationship of the number of fungicide sprays on the raw pH in a set of 15 species. It is suggested that this simple new multifaceted parameter can deserve interest.

Biological Networks: An Introductory Review

Oct 2018 DOI 10.14302/issn.2326-0793.jpgr-18-2312
Saad Zaghloul Salem MohammadCorresponding author Professor of Medical Genetics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt

All aspects of life activities in living cells are mediated/executed and regulated by a vast number of networks, comprising a wide spectrum of components, starting with simple biomolecules and ending with the whole organism, and functioning within a precisely organized tight framework. Proper mediation of cellular activities necessitates their inclusion within the context of structured and organized network systems capable of regulating/coordinating and synchronizing the countless numbers of biological processes occurring within living cells. The number of biological networks and pathways within the living cell is considerably huge, being dependent on the structural complexity and functional capabilities of the cell. Pathogenesis and progression of human diseases result from functional disturbances of biological networks within the cell as disturbed network function leads to deleterious effects on physiological processes dependent on, and mediated by, affected network(s). Ensuing pathological processes, defined by the nature of disturbed networks and the specific organs or tissues affected, pave the way for the development of pathognomonic and characteristic disease entities. As most network functions are dependent on relatively small number of key regulatory biomolecules, i.e. enzymes/proteins and signal transducing factors, it follows that functional disturbances of biological networks and pathogenesis of disease states can be attributed, in most instances, to quantitative and/or qualitative abnormalities of these key regulatory molecules. Study and analysis of the structural designs and the functional mechanisms of biological networks would have crucial and important impacts on many theoretical and applied aspects of biology, in general, and of medical sciences in particular. Meticulous study of biological networks represents an important and integral aspect in study of biology. Interpretation and analysis of key information deduced from observing and analyzing structural designs and functional characteristics and dynamics of biological networks discloses and defines the basic framework within which life activities in living cells are initiated, adapted to physiological requirements, maintained, and terminated upon completion of their aims. More important, however, is the contribution of this information to proper understanding of the different mechanisms responsible for regulating and synchronizing the functions and performances of the vast spectrum of different network categories within the cell. In addition to its vital scientific significance, discovering and defining the key pivotal structural and regulatory molecules within life-mediating networks, and along different pathways responsible for controlling functional dynamics of the network, represent an indispensable diagnostic approach insistent for designing proper therapeutic approaches to diseases caused by network defects.

Application of Nanotechnology for the Preservation of Red Blood Cells

Sep 2018 DOI 10.14302/issn.2689-2855.jan-18-2342
Belousov AndreyCorresponding author Laboratory of Applied Nanotechnology of Belousov.

This study was devoted to the learning of the use of nanotechnology to correct the functional activity of red blood cells (RBCs) at the storage stages at a positive temperature. It was established that saline NaCl, which had previously been processed by magnetite nanoparticles (ICNB) had a marked membrane-stabilizing effect, inhibits hemolysis and increasing the sedimentation stability of preserved RBCs. The complex analysis of the obtained data allowed to determine the primary mechanisms effect of the saline NaCl, which had previously been processed by ICNB on the preserved RBCs. The proposed method of additive modernization of preserved RBCs was adapted to the production process. The optimization results were obtained in creating a simple and practical method of additive modernization of preservation solutions that does not violate the compliance requirements, improves the quality, efficiency and safety transfusion of RBCs.

Is the Measles Virus Indeed Involved in Carcinogenesis? – Commentary

Aug 2018 DOI 10.14302/issn.2641-9181.ijnr-18-2195
Benharroch DanielCorresponding author Independent Physician, Department of Pathology, Soroka University Medical Centre and Faculty of health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Objectives: An association between the measles virus and Hodgkin lymphoma has been disclosed by our laboratory in Beer-Sheva, starting in 2003. We question the refutation of our study and the absence of interest among experts. Methodology: It was based on immunohistochemistry with commercial, as well as experimental anti-measles antibodies. It relied also on RT-PCR and in situ hybridization evidence of measles virus RNA. Key Results: At this stage (2004), the link between the virus and the lymphoma was essentially descriptive. The first and last response to our challenge appeared in 2007, in the form of doublet articles, in the same issue of a major cancer journal. The two European research groups responding, rejected categorically our findings by proposing different arguments. Major Conclusion: As reservations to these reactions became soon apparent, a series of papers from our laboratory were published. These articles concerned the evidence of a relationship between the measles virus and additional categories of cancers. Different malignancies in which this virus was not expressed at all, were also described. A further study suggested a mechanism by which the measles virus may activate lymphomagenesis in classic Hodgkin lymphoma. To our dismay, and in spite of repeated calls to verify the various results, no further response was obtained from international experts.

Molecular and Cell Biological Considerations in the Initiation and Development of Sporadic Non-Hereditary Solid Cancers  

Aug 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2183
F. Niculescu VladimirCorresponding author Cell Biologist, Germany, Kirschenweg 1, 86420 Diedorf

This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.

Prospect of Graphene Interface Control for Tougher Ceramic Composites

Jun 2018
Kendall KevinCorresponding author University of Birmingham, B15 2TT, UK

Graphene-Ceramic Composites (GCCs) have been little studied compared to graphene-polymer composites 1. Recent reviews 23 indicate that both mechanical and electrical property ceramic improvements can be obtained by mixing small quantities, typically 1 to 15% of graphene material with a ceramic precursor, then compacting and sintering. The greatest effect is on the electrical properties. The electrical conductivity of a material was first shown to rise by several orders of magnitude for only a 1% volume addition of graphene as in polymer composites 4 but the stiffness, strength and toughness only increased by 20-160% or so at 5% addition, a rather minor improvement compared to significant increases caused by slight ceramic process changes. Some crack bridging and pull-out mechanism was observed by electron microscopy in graphene-alumina composites, though the effects were modest. Surface friction and wear improvements of around 100% were also notable. This paper seeks to show that much higher toughness increases might be produced using the method pioneered by Clegg et al 5, where the graphite interlayers are replaced with graphene to produce improved ordered interfaces with reliable coverage and consistent interface fracture energy, enabling an increase in the fracture resistance of the ceramic by two orders of magnitude.

Energy Conservation Open Access

The Study on Dual Fuel Spray and Characteristics of Combustion of Diesel, Natural Gas and Dual Fuel

Jun 2018 DOI 10.14302/issn.2642-3146.jec-18-2135
Wang QianCorresponding author School of Energy and Power Engineering, Jiangsu University, 301 Xuefu Rd., 212013 Jiangsu, China.

Combustion of fossil fuels provides around 88% of total energy supply for modern society, and meanwhile causes many environ mental problems and social problems such as air pollution and energy crisis. Therefore,both at home and abroad are focusing on the research and development of natural gas engine recently. However, the mass production and application of this kind of engine are restricted by some unsolved technical difficulties. This paper explored the injection, combustion and emission processes of diesel/ natural gas and dual fuel engine based on Chemkin II, Fire software and Schlieren method. The experimental study on the mixing process of dual fuel jet was carried out by using high-speed Schlieren method in a constant volume bomb. Based on the Fire software, and then applied to Chemkin II software to analyze the effect of the initial temperature and pressure on the net heat production and combustion emissions. The results show that Dual fuel mechanism is capable of producing different heat production behaviors when varying the initial pressure and temperature CO2 emissions are minimized by changing the initial pressure above or below the atmospheric value. However, CO emissions are peaked when diesel fuel is used. The dual fuel engine minimizes the CO emissions amount caused by diesel fuel. Increasing the initial pressure eliminates dual fuel CO2 combustion emissions. The research of this paper is important to optimize the in cylinder combustion processes of natural gas engine, and have a certain important meaning to guide the development of diesel ignition dual fuel engine.

The Effect of Laser Irradiation on Reparative Osteogenesis

Apr 2018 DOI 10.14302/issn.2577-2279.ijha-18-2030
A. Kiryanov N.Corresponding author Izhevsk State Medical Academy, Russia.

Introduction: The use of non-medicinal facilities for correcting processes in various pathological conditions is one of the most urgent problems of modern medicine. Purpose of the Work: To study the effect of low-intensity infrared laser radiation on reparative bone formation and angiogenesis in bone regeneration which is formed in treatment of fractures under conditions of transosseous osteosynthesis. Material and Methods: A tibia fracture was modeled experimentally in rats in the control and experimental groups. Reposition and fixation of fragments were performed. The fracture zone in the experimental group animals was exposed to the impact of pulsed infrared laser irradiation of low intensity. Animals from the control group underwent the impact simulation. The operated bones were investigated using the methods of X-ray, light and electron microscopy, X-ray electron probe microanalysis. Results: It was established that laser radiation exposure sessions activated fibrillogenesis and angiogenesis, accelerated compacting of newly formed bone tissue and increased its maturity while primary fracture healing occurred. Prolonged capillary dilatation and endothelium-dependent vasodilation, intensive capillarogenesis were noted after sessions of laser therapy in bone regeneration. Endothelial outgrowth was formed in the lumen of the vessels forming capillary buds that propagate along the “mother” vessels (endovascular capillarogenesis). Conclusion: The data obtained revealed a possible mechanism of laser radiation exposure at the level of a whole organism and proved the effectiveness of its application in clinical practice at the early stages of patient rehabilitation under conditions of transosseous osteosynthesis.

Current Status and Future Perspectives of Gene Therapy for Heart Failure

Apr 2018
Li DongyeCorresponding author Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 221006, Xuzhou, Jiangsu, PR China

Heart failure(HF) is a disease with high morbility and mortality. The benefits of current pharmacological and device therapy for survival outcomes of patients with HF are limited. Gene therapy represents a novel promising strategy in treating HF, as it can theoretically normalize the aberrantly expressed genes and their regulatory mechanisms permanently. However, the translation of gene therapy for HF from bench to bedside has been less successful. There are many challenges ahead for gene therapy, especially in the areas of selection of the optimal targets, the needs for developing delivery systems and the improvement in design of clinical trials. In this review, we summarize the most promising gene targets which have been used in experimental and clinical studies for treating HF, highlighting the results from several clinical trials. We also review the latest development in gene therapy vectors and delivery methods, aiming to provide directions for future studies.

Veterinary Healthcare Open Access

Lipopolysaccharide Prompts Oxidative Stress and Apoptosis in Rats’ Testicular Tissue

Mar 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2013
A Halawa AmalCorresponding author Department of Forensic Medicine and Toxicology, Faulty of Veterinary Medicine, Mansoura University, Mansoura, Egypt

Lipopolysaccharide (LPS) is a component of the outer membrane of gram negative bacteria. LPS challenging allows switching transcription of proinflammatory cytokines on via over stimulation of Toll-like receptors (TLRs) signaling pathway with subsequent pathogenic inflammatory response. We investigated the possible reproductive toxicity of LPS in male Wister albino rats. Oxidative stress markers, antioxidant status and caspase-3 activity were analyzed in testicular tissues of rats exposed to either saline or LPS (4 mg/kg BW, ip; 0.18 of the LD50). The samples were collected at 6 h and 72 h after injection of LPS. A significant reduction in testicular reduced glutathione (GSH), glutathione-S-transferase (GST) and superoxide dismutase (SOD) was observed at 72 h compared to control group. Total antioxidant capacity was decreased at 6 h with additional significant reduction at 72 h. Catalase activity was reduced significantly at both 6 and 72 h. Malondialdehyde (MDA) was increased (P ≤ 0.05) in LPS injected rats without variation between 6 and 72 h. A significant increase in nitric oxide (NO) was observed at 72 h after injection. A time-dependent increase in LPS-treated groups was observed in the concentration of caspase-3.Histopathological analysis revealed degenerative changes and necrosis of seminiferous tubules after 6 h with further accumulation of eosinophilic edematous transudate in its lumen after 72 h. In conclusion, by increasing time of exposure, LPS induced lipid peroxidation, oxidative stress, reduced testicular antioxidant capacity and encouraged testicular apoptosis which could be possible mechanisms for impairment of testicular function.

Musings in Physiology

Feb 2018 DOI 10.14302/issn.2578-8590.ipj-17-1919
Warring-Davies KennethCorresponding author Consultant Clinical & Cardiovascular Physiologist, Research Graduate University of Huddersfield.

A reflective piece touches on core physiological concepts and experimental approaches, linking basic mechanisms to clinical insight and education.

Emerging Roles of Plant Circular RNAs

Feb 2018 DOI 10.14302/issn.2832-5311.jpcd-18-1955
Zhu Qian-HaoCorresponding author CSIRO Agriculture and Food, GPO Box 1700, Canberra, ACT 2601, Australia

Circular RNAs (circRNAs) are covalently closed single-stranded loop RNA molecules with or without protein coding capability. CircRNAs were previously considered to be splicing intermediates or artifacts but are now found to be pervasively expressed in all eukaryotes studied with some demonstrated to have important molecular functions in various biological processes. CircRNA is now a hot study topic of molecular biology. In this review, we summarize the progress achieved so far on plant circRNAs, including identification and functional characterization, compare the similarities and differences of circRNAs between plants and animals, and discuss the challenges for confident detection and functional investigation of plant circRNAs. Similar to what have been found in animals, plant genomes contain a large number of circRNAs that potentially regulate a wide range of biological progresses related to plant development and biotic/abiotic responses. Despite only a few plant circRNAs have been functionally characterized, novel function/mechanism that has not been reported in animals was revealed, implying more exciting findings about plant circRNAs are expected in future studies.

The Therapeutic Effect of Bilateral Alternating Stimulation Tactile Form Technology on the Stress Response

Feb 2018 DOI 10.14302/issn.2576-6694.jbbs-18-1887
S. Hageman NathanCorresponding author David Geffen School of Medicine at UCLA, Los Angeles, CA Corresponding Author

The application of bilateral alternating stimulation in tactile (BLAST) form technology, a non-invasive, somatosensory-based method, has been shown to modulate the electrical activity of brain networks that mediate the stress response, resulting in a stress-reducing effect in individuals with high reported levels of anxiety, such as post-traumatic stress disorder (PTSD). In this study, we examined archival data from a heterogeneous group of users (n = 1109) of BLAST technology via Touchpoints, a novel BLAST-based treatment modality, all of whom had high self-reported levels of stress and anxiety. Ratings of levels of emotional stress and bodily distress on a scale of 0 (no stress/distress) to 10 (worst stress/distress of one's life) before and after the application of Touchpoints for 30 seconds were entered into an app. Results showed a statistically significant reduction in the levels of both emotional stress and bodily distress, 62.26% and 50.502%, respectively, after 30 seconds of BLAST technology was applied. This demonstrates a clear benefit of BLAST on the stress response, reducing both emotional stress and disturbing body sensations. Recent work examining EEG changes after BLAST technology is applied suggests that BLAST may reduce sympathetic activation by reducing the electrical activity of key areas of the salience network. Further work will more precisely characterize the effects of BLAST, its potential clinical uses, and the mechanisms of actions behind it’s apparent stress-reducing effects.

Fractures of the Humeral Condyles in Children – A Review

Feb 2018 DOI 10.14302/issn.2766-6204.jmpt-17-1913
NF TepeneuCorresponding author Department of Pediatric and Adolescent Surgery, General Hospital Klagenfurt, Austria

The three most common elbow fractures classically reported in pediatric orthopedic literature are supracondylar (50–70%), lateral condylar (17–34%), and medial epicondylar fractures (10%). The mechanism of injury varies, but the most commonly described mechanism involves a fall on an outstretched hand with varus, valgus or rotational force or a combination thereof. The vectors of force and the degree of chondro-osseous development dictate the type of injury incurred. A review of the literature was conducted to see the most frequent injuries and complications.

International Journal of Chemotherapy and Practice; A Novel Journal for Therapeutic Researches

Feb 2018
Oner CagriCorresponding author Maltepe University, Faculty of Medicine, Department of Medical Biology and Genetics

An inaugural editorial presents the journal's scope spanning chemotherapy research and clinical practice. It invites translational work linking mechanisms, regimens, and real‑world outcomes with an emphasis on safety and effectiveness.

Substrate Stiffness Influences the Time Dependence of CTGF Protein Expression in Müller Cells

Jan 2018 DOI 10.14302/issn.2578-8590.ipj-17-1910
J Foster WilliamCorresponding author Department of Physics, University of Houston, Houston, TX, USA

Following ocular trauma and retinal detachment, gliotic changes in the retina may develop over the subsequent month, a process known as PVR (proliferative vitreoretinopathy). There have been no successful therapeutic interventions to inhibit PVR. The protein CTGF (Connective Tissue Growth Factor) has been associated with retinal PVR and other fibrotic diseases of the retina in clinical studies but the mechanistic link between different pathologies and retinal gliosis has not been determined. In addition, CTGF has been previously noted to be associated, in some cases, with YAP/TAZ (Yes-associated protein and Tafazzin protein complex), transcriptional regulatory proteins that change subcellular localization in response to mechanical cues, such as the stiffness of the underlying material. We have previously shown that the mRNA for CTGF is markedly (100-fold) upregulated in retinal Müller cells grown on soft substrates. In order to evaluate if the mechanism by which mechanotransduction modulating CTGF production in retinal Müller cells involves the YAP/TAZ complex, this study tests the influence of substrate stiffness on the time dependence of CTGF protein expression, as well as subcellular localization of YAP/TAZ using a conditionally-immortalized mouse retinal Müller cell line plated on laminin-coated, polyacrylamide substrates of varying elastic modulus. Changes were assayed using immunohistochemistry and ELISA (Enzyme-Linked ImmunoSorbent Assay). In retinal Müller cells, the relationship between elastic modulus and the pattern of CTGF protein expression was bimodal, with CTGF levels rising more rapidly for cells on hard substrates and more slowly for cells grown on soft substrates. In addition, nuclear localization of YAP/TAZ corresponded directly to the maximum CTGF expression.

Acute and Chronic Wound Fluid Inversely Influence Wound Healing in an in-Vitro 3D Wound Model

Dec 2017 DOI 10.14302/issn.2640-6403.jtrr-17-1818
Manuela BesserCorresponding author University Witten/Herdecke, Centre for Biomedical Education and Research (ZBAF), Dpt. Of Translational Wound Research

If a wound progressively heals or the healing process is impaired is basically influenced by the surrounding milieu. This is reflected by the wound fluid. Its specific composition triggers the migration, proliferation and differentiation of dermal and epidermal cells which so far was not sufficiently examined in 2D cell culture models. The influence of the different wound entities was analyzed on a newly implemented three dimensional in-vitro model, which improved the transferability to the in-vivo situation. The influence of pooled wound fluids from patients suffering from acute or chronic wounds were investigated within a time period of 10 days after wound application. Histological and immunohistochemical analyses were performed addressing the impact of AWF and CWF on regeneration, such as cell proliferation, fibroblast activity and cell migration. AWF slightly stimulated fibroblast migration while CWF inhibited their activation and migration. The CXCR4- immunopositive population was continuously decreased compared to the control and AWF treatment. The expression of FAP was enhanced under AWF and medium. In keratinocytes CWF massively stimulated cell proliferation initiating on day six after injury. The presence of 10% CWF inhibited fibroblast activation and migration and induced the degradation of the collagen matrix. Keratinocytes were stimulated to proliferate, resulting in healing inhibiting hyperplasia. Transferred to human wounds, no effective wound closure would be achieved because of the de-regulation of pro-proliferative and migration-stimulating factors and a degraded extracellular matrix. This newly implemented 3D study model represents a novel appropriate in-vitro system for studying healing mechanisms and potential therapeutic applications.

Blockade of Programmed Cell Death Protein-1 Pathway for the Treatment of Melanoma

Nov 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1760
Bhandaru MadhuriCorresponding author Department of Dermatology, University of British Columbia, Vancouver, Canada

Metastatic melanoma is a very deadly type of skin cancer with poor prognosis and low 5-year survival rates. Until recently, patients with metastatic melanoma had very few treatment options, which only included dacarbazine and aldesleukin. In 2011, the first checkpoint blocker, ipilimumab was approved for the treatment of unresectable metastatic melanoma but its success was eclipsed by low response rates and high incidence of adverse events. Later in 2014, anti-PD-1 antibodies, nivolumab and pembrolizumab were approved for the treatment of metastatic melanoma. With comparatively high response rates and manageable safety profile, PD-1 blockers were remarkably successful in the treatment of melanoma and also other cancer subtypes such as non-small cell lung cancer and metastatic urothelial carcinoma. This article highlights the success of anti-PD-1 antibodies, discusses the mechanism of PD-1:PD-L1/2 pathway, responses of melanoma patients to PD-1 blockers and the research on improving response rates to PD-1 blockers.

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