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100 articles
Diseases Open Access

Toward Better Care for Sickle Cell Disease in Nigeria: A Review of Challenges and Interventions

Dec 2025 DOI 10.14302/issn.2997-1977.jd-25-5754
Valentine Olagunju GraceCorresponding author

With more than 150,000 affected infants annually, Nigeria bears the largest burden worldwide of sickle cell disease (SCD), making it a significant public health concern. The management of SCD in Nigeria is challenging, despite advancements in medical research and increased knowledge. This review examines the numerous issues surrounding SCD in the nation, including the financial burden on affected families, the lack of specialized care facilities, the absence of newborn screening programs, the sociocultural stigmatization of SCD, and restricted access to high-quality healthcare. Additionally, inadequate public health education and a lack of coordinated national policies result in delayed diagnosis and suboptimal treatment outcomes. We also highlighted recent efforts and recommendations aimed at improving early detection, comprehensive care, and community support. Addressing these challenges through expanded health education and enhanced healthcare infrastructure is essential to reducing morbidity and mortality associated with SCD in Nigeria.

Ethics of Modern Stem Cell Research and Therapy: Current Critical and Interdisciplinary Perspectives

Sep 2024 DOI 10.14302/issn.2474-7785.jarh-24-5212
R. von Schwarz ErnstCorresponding author

From an academic and clinical point of view, stem cell therapy represents one of the most promising advances in modern medicine, with the ability to partially induce the regeneration of acutely injured or chronically damaged tissues. Stem cell research provides new opportunities for the treatment of various conditions, among them diabetes mellitus, HIV, cardiovascular diseases, and neurodegenerative illnesses. Stem cell therapy is currently not FDA-approved in the US (except for certain blood cancers). While bioethics and religion have mostly discussed the source of cells, i.e., embryonic cells that require the destruction of embryos versus adult tissue for research purposes, we also discuss the controversies with regard to currently offered therapies, and marketing of unapproved procedures from a scientific, clinical, and religious viewpoint.

Fetal Surgery Open Access

RETRACTED: Leap into Fetal Surgery; In Utero Placental Mesenchymal Stem Cell Therapy, A Contemporary Approach to Treating Myelomeningocele

Apr 2024 DOI 10.14302/issn.2997-2086.jfs-23-4651
Osama Siddiqui MuhammadCorresponding author

This article has been retracted on April 10, 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2997-2086.jfs-25-5857) Myelomeningocele (MMC), a class of spina bifida is a type of neural tube defect. According to the U.S. Centers for Disease Control and Prevention, each year approximately 1,400 babies born in the United States have spina bifida. The disease manifests with the lack of skin and bone covering the caudal part of the spinal cord. The patient developing such a condition often develops lifelong impaired lower limb mobility accompanied by hydrocephalus, and urinary and bowel incontinence. The available interventions include prenatal and postnatal surgery to fuse the dura. Prenatal surgery performed before 26 weeks of gestation reduces the risk of death or the need for ventriculoperitoneal shunting. It also enhanced results on a comprehensive index for mental and motor function. When compared to postnatal surgery, prenatal surgery reduces the manifestation of several secondary outcomes, including the degree of hindbrain herniation seen in the Chiari II malformation. Stem cell therapy for MMC on animal models of chick, ovine, and rodents with reported cases 15/63, 15, and 136, respectively, using human Embryonic Stem Cells (hESCs), Neural Stem Cells (NSCs), Mesenchymal Stem Cells (MSCs) showed significant coverage of MMC defect and slight neurogenesis was also observed. With an understanding of medical literature about in-utero regenerative capacity, it is to be appreciated that placental stem cells surgically seeded within a biocompatible scaffold of the cell patches can play a part in alleviating the spinal cord manifestation associated with MMC. Documented animal studies show that incorporating Placental Mesenchymal Stem Cells in prenatal surgery has reported improved neurogenesis and lower limb mobility. In an ovine myelomeningocele model, the development of in-utero myelomeningocele repair with human Placental Mesenchymal Stem Cells seeded onto an extracellular matrix (PMSC-ECM) enhances motor findings. The clinical trial for the first stem cell therapy on human subjects known as the “CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele.” is expected to be finished by 2030. So far, the cases undergoing treatment have shown significant leg movement and a greater degree of bowel and urinary control. This FDA-approved clinical trial is envisioned to be the future of treating MMC.

Changes in Cellular Morphology in Bronchoalveolar Lavage Fluid of Children with Mycoplasma Pneumoniae Pneumonia

Apr 2024 DOI 10.14302/issn.2641-4538.jphi-24-5044
Li ShujunCorresponding author

Objective To study changes of cell morphology in BALF in children with Mycoplasma pneumoniae pneumonia (MPP). Methods From December 2021 to May 2022, a group of 32 children diagnosed with Acute MPP and admitted for treatment in the Pediatrics Department and PICU of the First Affiliated Hospital of Xinxiang Medical University were selected for our study. These patients underwent bronchoalveolar lavage as part of their clinical assessment. For comparison, we included a control group comprising 10 children who were not infected but had bronchial foreign bodies. We investigated the cellular composition in the bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining and microscopic evaluation, aiming to understand the relationship between shifts in cell proportions and extra-pulmonary symptoms associated with MPP. Results In this study, a total of 42 cases were enrolled, with 32 cases in the study group and 10 cases in the control group. There were no statistically significant differences in gender, age, height, weight, and BMI between the two groups (p > 0.05). The study group exhibited significantly higher levels of neutrophil percentage (GRA%), CRP, D-dimer, and LDH in blood routine tests compared to the control group (p < 0.05). Furthermore, the proportions of neutrophils (%) and macrophages (%) in BALF were significantly higher in the study group compared to the control group (p< 0.05), while the proportion of lymphocytes (%) in BALF showed no statistically significant difference between the two groups (p> 0.05). Conclusion In the acute phase of MPP in children, BALF is predominantly composed of neutrophils. A lower proportion of lymphocytes in BALF is associated with a higher incidence of extra-pulmonary manifestations and longer hospitalization duration.

Duffy Red Cell Antigen Phenotype among Indigenous Pregnant Women attending Antenatal Clinic at Federal Teaching Hospital Gombe, Gombe State, North Eastern Nigeria

Dec 2023 DOI 10.14302/issn.3070-1937.ijbt-23-4714
M. Gaji AhmedCorresponding author

Background and Objectives Duffy (FY) blood group system is implicated in transfusion incompatibilities and haemolytic disease of the foetus and newborn (HDFN). The primary objective was to determine the Duffy phenotype among indigenous pregnant women in Gombe, Gombe State, Nigeria. Materials and Methods This was a Cross sectional study where simple random sampling was employed on consented participants. Two hundred and fifty nine pregnant women attending antenatal clinic at Federal Teaching Hospital Gombe were randomly recruited into the study. About 3mls of blood was taken, and Duffy antigen typed by standard tube technique (LORNE LABORATORY UK). Results Among the Indigenous tribe, the percentage of Fy(a+b+) was seen in 2.2% of Fulani and 3.4% of Tangale, Fy(a+b-) phenotype was seen in 4.3% of Tangale, 6.8% of Fulani,9.5% of Tera, 10.3% of Hausa and 10.5% of Waja. Fy(a-b+) phenotype was seen in 5.3% of Waja, 7.6% of Fulani,8.7% of Tangale, 9.5% of Tera and 12.5% of Bolawa. Fy(a-b-) phenotype was seen in 2.4% of Tula,6.4% of Bolawa,7.3% of Waja, 7.8% of Tera, 17.8% of Tangale, 11.8% of Hausa and 46.5% of Fulani. About 84.6% of the study population had the null Duffy phenotype. Conclusion The research showed the phenotypic distribution of Duffy blood group among the study participants with relatively high percentage of null Duffy phenotype hence possible risk of alloimmunisation.

Veterinary Healthcare Open Access

Camel Brucellosis in Ethiopia: Seroprevalence and Associated Risk Factor

Oct 2023 DOI 10.14302/issn.2575-1212.jvhc-23-4532
Abda Neja SultanCorresponding author

Camels are a significant source of income for nomadic populations in many developing countries, including Ethiopia. Camels are well adapted to dry and semi-dry regions, providing income, food security, and transportation. However, camel production and productivity are constrained by infectious diseases, such as brucellosis, which is a highly infectious bacterial disease that affects camels and humans worldwide. Brucellosis causes significant economic losses due to abortion, low herd fertility, and decreased milk production. In Ethiopia, the prevalence of camel brucellosis varies depending on factors related to the host, agent, climate, and management system, with a reported prevalence ranging from 0.5% to 11.9%. Accurate diagnosis of camel Brucellosis is essential for herd-based screening of animals. Although culturing the pathogen is the preferred method for diagnosis, serological tests such as Rose-Bengal plate test (RBPT), Enzyme-linked immunosorbent assay (ELISA), and Complement fixation test (CFT) and polymerase chain reaction (PCR) assays have been developed. Implementing effective diagnosis and surveillance systems to control the spread of brucellosis in animals and humans is very important, on top of awareness campaigns, vaccination programs, and suitable laboratory establishment recommended. Continued research is essential to maintain the health and productivity of camel populations, particularly in pastoral areas where camels play a significant role in the livelihood of communities. Therefore, the present paper views the seropositive prevalence and potential risk factors associated with camel brucellosis in Ethiopia.

Low Seroprevalence of Brucella Spp. among Remote Colombian Communities from the Sierra Nevada De Santa Marta

Aug 2023 DOI 10.14302/issn.2641-9181.ijnr-23-4658
Oakley ReginaCorresponding author

Brucella species cause a high burden of disease globally, infecting both humans and animals; however, One Health has been under-appreciated in Colombia. This study aimed to determine the seroprevalence of Brucella spp. in two remote indigenous communities from the Sierra Nevada de Santa Marta, Colombia. These communities live in close contact with their livestock, indicating a potential susceptibility to zoonotic pathogens. The livestock routinely kept by these communities include cattle, small ruminants and pigs, the known hosts of human pathogenic Brucella spp.. A low level of exposure to Brucella spp. was documented, with only one positive participant among 539 participants (0.2%; 95% CI 0.0 – 1.0). Nevertheless, due to the high risk that zoonoses pose, we recommend discussions with the community for the potential establishment of One Health surveillance studies for the early detection and prevention of future zoonotic disease threats.

The Impact of EDTA And Selenite on The Stability of Insulin in Cell Culture Media

Jun 2023
S. Prakasha Gowda A.Corresponding author

Insulin is a frequent peptide hormone addition in serum-free mammalian cell culture media. It contributes in a variety of biological functions, including as promoting cell proliferation, cell cycle progression, and glucose uptake. However, it is unknown how stable insulin is under in vitro cell culture media treatment conditions. The instability of insulin in aqueous solutions has caused a number of issues, necessitating the development of new therapeutic strategies that can keep insulin stable and functioning. Such choices are required to accommodate updated insulin delivery guidelines as well as the storage and transportation of insulin. To preserve structural and functional integrity, protein medicines are frequently stabilized with antioxidants in aqueous solutions. In the present study, the effects of the antioxidants disodium ethylenediaminetetraacetic acid dihydrate (EDTA) and sodium selenite (Se) and their ability to scavenge free radicals on insulin stability in the medium Dulbecco's Modified Eagle Medium (DMEM) and Roswell Park Memorial Institute (RPMI) were examined. To investigate the stability of human recombinant insulin, in vitro serum-free DMEM and RPMI media were utilized for 5 days at 37˚C containing different EDTA and Se concentrations. Reversed phase high performance liquid chromatography (RP-HPLC) was used to detect and quantify insulin. Sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE) electrophoresis was used to assess conformational stability. The results demonstrated that, when EDTA and Se were added separately to DMEM and RPMI media, insulin stability was improved compared to when neither compound was added.

Challenger Treatment of Various Cancers with T Cells Engineering

Apr 2023
Gobato RicardoCorresponding author

Through T-cell engineering, researchers at the California South University (CSU) Cancer Research Institute (CRI) have shown that tumor growth can be stopped in a variety of cancers and prevented from spreading to other tissues. Findings from this study are the result of decades of research by Professor Ph.D. A. Heidari and our team of CSU, who discovered a protein called AH that can inhibit the growth and spread of cancer cells in several different ways. They become in the tissues of the body. The T cells were armed with MDA-7/AH to target cancer more widely. The engineering of T cells to produce MDA-7/AH causes cancer cells to be destroyed regardless of the expression of the target molecules. The tumor site is often very hostile to immune cells. It was found in the research that MDA-7/AH can help T cells proliferate and increase the number of cancer cells. The T cells were armed with MDA-7/ AH to target cancer more widely. The engineering of T cells to produce MDA-7/AH causes cancer cells to be destroyed regardless of the expression of the target molecules. The tumor site is often very hostile to immune cells. We discovered that MDA-7/AH can help T cells proliferate and increase the number of cancer cells.

Non-Specific Steroid Cell Tumor of The Ovary: Case Report And Review of The Literature

Dec 2022 DOI 10.14302/issn.2574-4526.jddd-22-4151
Darouichi M.Corresponding author Institute Medical Champel, 1206.Champel, Geneva, Switzerland

Steroid cell tumors of the ovary are particularly rare, secreting sex hormones, characterized by steroid cell proliferation and represent only 0.1% of all ovarian tumors. They are classified into three subtypes according to their cell of origin: stromal luteoma, Leydig cell tumors and a third subtype of unknown lineage corresponds to a not specified steroid cell tumor (SCT-NOS). This third subtype accounts for 60% of steroid cell tumors. The clinical manifestations of SCT-NOS can take many forms, including pain, abdominal distension, but perhaps the most visible presentations are those related to hormonal activity and virilization of the tumor. We present a rare case of a 48-year-old woman with vaginal bleeding and a history of trunk obesity, hirsutism for 2 years and hypothyroidism with hormone replacement therapy. Clinical examination revealed a characteristic of obesity, virilization. Serum testosterone was 3.62 µg / L and CA-125 was 40.67. Magnetic resonance imaging identified a left ovarian solid mass and histopathology confirmed a steroid cell tumor not specific. The patient underwent exploratory laparotomy and left salpingoophorectomy. Macroscopically, the mass is well circumscribed, solid, homogeneous and yellowish. Microscopically, the tumor is mainly composed of eosinophilic or vacuolar granular cytoplasm. Immunohistochemistry showed that the tumor cells were strongly positive for inhibin. The postoperative period was uneventful. Through this rare observation, we will discuss the aspects that characterize this type of tumor and present some guidelines to be used in the differential diagnosis, as well as the difficulties encountered in the clinical, radiological and therapeutic fields.

Evaluation of A Nutrition Feeding Algorithm for Children and Adolescents Undergoing Haematopoietic Stem Cell Transplantation (HSCT)

May 2022 DOI 10.14302/issn.2379-7835.ijn-22-4190
Bartle JodieCorresponding author Department of Nutrition & Food Services, Royal Children’s Hospital, Melbourne.

Background Nutrition support during the acute phase post allogeneic haematopoietic stem cell transplantation (HSCT) is required to optimise short- and long-term outcomes for children. An algorithm was developed and evaluated to assist clinicians to make objective and consistent enteral feeding decisions. Methods The algorithm was evaluated on all patients who underwent allogeneic HSCT treatment between November 2017 - February 2019. Results Of the 48 patients, 43 had a nasogastric tube (NGT) inserted, of which 36 patients received a hydrolysed peptide-based formula, 5 patients received a whole protein formula only and 2 patients were fed an amino acid-based formula. Parenteral nutrition (PN) was used in 41 of the patients. Eleven did not have an NGT in-situ at the commencement of HSCT. Of the remaining 37 patients, 26 followed the algorithm and 11 patients did not comply. The group of patients who did not follow the algorithm had the longest median length of stay (LOS) of 49 days. Patients receiving only EN had the lowest median LOS of 30 days. The two groups that reported better weight outcomes were those who followed the algorithm and those who were fully EN fed. Conclusions Effective use of the HSCT feeding algorithm indicated improved patient outcomes for children undergoing HSCT, with better weight outcomes and reduced LOS. Recommendations to improve the efficacy and compliance of the algorithm include regular education/input to the oncology medical teams to better understand objective thresholds for EN and PN commencement.

Stem Cell Differentiation Stage Factors (SCDSFs) Taken from Zebrafish Embryo during Organogenesis and their Role as Epigenetics Regulators able to Reverse Neurosensory Hearing Loss

Feb 2022 DOI 10.14302/issn.2379-8572.joa-22-4072
Mario Biava PierCorresponding author Centro Medico Turati, Piazza Cavour 1, Milano (MI)

This translational paper discusses differentiation‑stage factors from zebrafish embryos as epigenetic regulators with potential to reverse neurosensory hearing loss. It outlines experimental evidence, delivery concepts, and research gaps.

Evolution of the Solid Human Tumor Cells Properties in Various Experimental Systems in Vitro

Jan 2022 DOI 10.14302/issn.2372-6601.jhor-22-4061
B. Danilova AnnaCorresponding author N.N. Petrov National Medicine Research Center of Oncology, Department of Oncoimmunology, 197758, Leningradskaya str., 68, Pesochny, Saint-Petersburg, Russian Federation

Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.

Body Fluids Open Access

An Uncommon Complication of Multiple Myeloma in a Post Bone Marrow Transplant patient–Plasma Cell Pleocytosis

Jan 2022
PrachiCorresponding author Senior Resident, Department of Pathology, Dharamshila Narayana Super speciality Hospital, New Delhi

This case report describes plasma cell pleocytosis occurring after bone marrow transplantation for multiple myeloma. The authors outline clinical presentation, cerebrospinal fluid findings, and differential diagnosis, emphasizing the need to consider hematologic relapse or CNS involvement in post‑transplant patients with neurologic symptoms. Management considerations and follow‑up strategies are discussed.

Veterinary Healthcare Open Access

Cytokine Expression in Peripheral Blood Mononuclear Cell Cultures Obtained from Cattle with Different Stages of Natural Mycobacterium bovis Infection

Dec 2021 DOI 10.14302/issn.2575-1212.jvhc-21-4034
Fernando Díaz-Otero,Corresponding author CENID-Salud Animal e Inocuidad. Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP). Carretera México-Toluca, Km. 15.5, C.P. 05110, Ciudad de México, México.

In bovine tuberculosis (bTB), cellular, humoral, or both types of immune responses have been observed. The purpose of this study was to examine the immune status of tuberculous cows based on the differential cytokine gene expression associated with Th1 (IFN-γ, IL-2), or Th2 (IL-4, IL-10) responses. Twenty-three (23) cows belonging to a dairy herd located in a rural region of the State of Hidalgo, México, were selected for the study. Single Intradermal Comparative Cervical Tuberculin (SICCT) Test, Interferon-Gamma (IFN-γ) Release Assay (BOVIGAM), and Enzyme-Linked Immunosorbent Assay (ELISA) were used for detection of cattle infected by M. bovis. Thirteen cows were positive to all the tests (Group 1); ten cows were positive only to ELISA (Group 2), and the remaining Group (Group 3, control) included cows negative to all the tests. Peripheral blood mononuclear cells (PBMC) from animals were in vitro stimulated by bovin purified protein derivative (PPD), avian PPD, and Concanavalin A (Con A) mitogen for 72h. Changes in the levels of expression of mRNA of the respective cytokines was measured by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) using β-actin gene as internal control. In group 1, PPD bovis and Con A-stimulated cells exhibited high production of IFN-γ, IL-2 and IL-4, but not IL-10. In contrast, PPD avium-stimulated cells displayed a low production of cytokine transcripts. In group 2, cells showed a significant production of IL-10 in response to bovine PPD (P< 0.001). In the control group, a high production of IFN-γ and IL-2 was observed only in Con A-stimulated cells. Post-mortem examinations in animals of group 1 showed slight and medium lesions in lymph nodes, whereas in group 2, the lesions were more extensive. Results indicate differences on gene expression levels of cytokines considered to determine balance in Th1/Th2 response among the evaluated groups. In addition, high levels of antibodies against M. bovis and high IL-10 expression in PBMC together are indicators of progressive bTB when both tuberculin test and IFN-γ assay are negative in tuberculous anergic cattle. Inclusion of serology and IL-10 cytokine expression in in the diagnosis checklist improves detection of infected cattle to help control bovine tuberculosis.

Identify the Effects of Ultra Weak Light on Alphacoronavirus and Vero Cells

Aug 2021 DOI 10.14302/issn.2692-1537.ijcv-21-3934
Chung Hee-ChunCorresponding author Department of Veterinary Medicine Virology Lab, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.

Coronavirus is causing many diseases and economic pain to humans and animals. The present study demonstrated how ultra weak lightcause changes in porcine epidemic diarrhea virus (PEDV) and Vero cells. Ultra weak lightactivates Vero cells by lowering pH of maintain media, but have proven no effect of killing the virus.

Elasticity Profile of Skin, Neuronal, Cardiac, and Skeletal Muscle Cells after Treatment with the Biofield Energy Healing-Based Proprietary Test Formulation

Jul 2021 DOI 10.14302/issn.2576-6694.jbbs-21-3819
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.

The present study aimed to evaluate the effect of the Trivedi Effect®- Biofield Energy Treated/Blessed Test formulation/item (TI) composed of minerals (magnesium, zinc, copper, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, alpha tocopherol, cyanocobalamin, and cholecalciferol), Panax ginseng extract, CBD isolates, and β-carotene on elasticity of skin, heart, muscle, and neuronal cells in the H9C2 (rat cardiomyocytes), C2C12 (mouse myoblast cells), HaCaT (human keratinocytes), and SH-SY5Y (human neuroblastoma cells) cell line in DMEM medium. The test formulation constituents were divided into two parts; one section was defined as untreated test formulation (UT), while the other portion of test formulation received Biofield Energy Healing/Blessing Treatment (BT) by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The test items were treated with Biofield Energy Healing/Blessing Treatment and divided as Biofield Energy Treated/Blessed (BT) and untreated (UT) test items. MTT data showed that the test formulation in various concentrations was found as safe and nontoxic in the tested concentrations with viability range from 73% to 307%. Young’s modulus (YM) is a measure of cell stiffness, a decrease in YM value indicates increase elasticity of the cells and vice-versa. YM in H9C2 cells were decreased by 9.6% and 66.1% in the BT-DMEM + UT-TI group at 0.1 and 1 µg/mL respectively, as compared with untreated test group. However, C2C21 cells showed increased YM by 443.9% at 1 µg/mL in the UT-DMEM + BT-TI group, while 869.6% increased YM in the BT-DMEM + UT-TI group at 1 µg/mL as compared with untreated test group. However, 314% increased YM was reported in the BT-DMEM + BT-TI group at 1 µg/mL as compared with the untreated test group. However, the value of YM was significantly decreased in the HaCaT cell line by 247.7% (at 1 µg/mL), 225.8% (at 0.1 µg/mL), and 97.9% (at 1 µg/mL) in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI group respectively, as compared with the untreated group. In addition, YM was significantly decreased in the SH-SY5Y cell line by 92.6%, 18.1%, and 26.6% at 1 µg/mL in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI group respectively, as compared with the untreated group. Overall, the results showed the significant decreased YM among the SH-SY5Y, HaCaT, and H9C2 cells, while it was increased in the C2C21 cell line. Thus, the mechanical properties of cells such as cellular function, including shape, motility, differentiation, division, and adhesion to its surrounding extracellular matrix were improved. Overall, it can be useful in many disease progressions with improved cellular elasticity and its associated complications/symptoms.  

The Dynamic Changes of White Blood Cell Count and Lymphocyte Count and Compare their Levels in the Early Stage of Covid-19

Jun 2021 DOI 10.14302/issn.2692-1537.ijcv-21-3862
Wang LingCorresponding author Department of Intensive Care Unit, People's hospital of Qiandongnan Miao and Dong Autonomous Prefecture, Kaili, Guizhou, China

COVID-19 is a new infectious disease, which needs to explore the clinical value of white blood cell count and lymphocyte to provide help for diagnosis and treatment.COVID-19 cases were Selected that admitted to 2 hospitals in Guizhou, China. WBC and LYM in the 1st day, in the 4th day and in the 7th day after onset were collected. There were not any differences in The WBC and LYM in the 4th day and the 7th day between the two groups.WBC and LYM in the 1st day in the moderate group were lesser than in the mild group. WBC and LYM were no dynamic changes in the mild group. In moderate group, WBC and LYM in the 1st day were lesser than in the 4th day. The levels in the 4th day and the 7th day were no differences. The conclusion was In the early stage of COVID-19, the WBC and LYM in moderate patients were significantly decreased within 4 days after onset, and could be restored to normal level after 4-7 days. However, no dynamic changes were observed in mild patients within 7 days.  

Veterinary Healthcare Open Access

Oxidative Status and Reproductive Characteristics in Female Cavies (Cavia porcellus L.) Fed on Aqueous Extract of Avocado (Persea americana Mill.) Seed

Apr 2021 DOI 10.14302/issn.2575-1212.jvhc-21-3759
Ferdinand NgoulaCorresponding author Animal Physiology and Health Research Unit, Faculty of Agronomy and Agricultural Sciences, University of Dschang, P.O. Box 188, Dschang, Cameroon

The present study was initiated to improve the farm animals’ productivity through the use of medicinal plants. More specifically, to determine in female cavies the effects of aqueous extract of avocado seed powder (AEASP) on the estrous cycle, the levels of LH, estradiol and tissues (ovarian and uterine) biomarkers of oxidative stress. For the trial, 24 female cavies with regular estrous cycles were selectedamong 40 trough observation of 4 estrous cycles. They were randomly shared into 4 groups of 6 females each, comparable in term of body weight (bw) (463.60±77.69 g). They received by gavage 1 mL/kg bw of distilled water for the control and 100, 200, 400 mg/kg bw of AEASP respectively for the groups EA100, EA200 and EA400. Subsequently, 3 estrous cycles were studied every day during all the treatment period. At the end, the cavies were slaughtered at the estrus phase; blood, ovaries and uterus were collected for analysis. As result, the AEASP significantly (p<0.05) increase the duration of the estrus phase in females of group EA100, without affecting significantly the duration of the estrous cycle as referred to the control. It significantly reduce the serum level of total cholesterol and increase (p<0.05) the serum concentration of LH in cavies of group EA100 compared to the control. AEASP significantly increase the serum concentration of estradiol in all treated females as referred to the control. It significantly increase the level of malondialdehyde (MDA) in the ovaries of the females of group EA400. In the uterine tissue, superoxide dismutase (SOD) increase significantly in the cavies of group EA200 compare to the control. We can conclude that the AEASP increase the duration of the estrus phase of cavies without affecting the duration of the estrous cycle. Subsequently, it increases the serum concentration of LH and estradiol.

Therapeutic Potential of Autologous Adipose Derived Mesenchymal Stem Cells in Human POI and Ovarian Aging

Mar 2021 DOI 10.14302/issn.2574-4372.jesr-20-3593
Hernández Víctor Manuel VargasCorresponding author Female Health Clinic, Mexico

Background Women play an important role in the work setting. This leads them to put off their motherhood, sometimes preventing them from getting pregnant. Delaying pregnancy face women with low ovarian response, such as in Premature Ovarian Insufficiency (POI) or Ovarian Aging (OA). There is no current treatment, although there is evidence of improving ovarian function by inyecting mesenchymal stem cells (MSC). Materials and Methods Prospective, observational study of 17 women who attended Pronatal Clinic from 2019 to 2020. Each patient was registered in Assisted Reproductive Treatment (ART) and was enrolled in ovarian treatment with an autologous adipose tissue Mesenchymal Stem Cell (AD-MSCs) protocol. Three groups were assembled: 1) Control: AMH >1.2 ng/mL, without AD-MSCs, 2) POI/OA: female infertility due to POI/OA with AMH <1.2 ng/mL and 3) Amenorrhea: female infertility due to POI/OA with amenorrhea and AMH <1.2 ng/mL. Variables: Age, weight, height, serum AMH, endometrial thickness, follicular size and number on day 2 and 11 of the menstrual cycle, oocyte number, number of blastocysts and pregnancy rate. Results Between month 2 and 5, after AD-MSCs inyection, POI/OA group showed an increase in follicle number (2 to 9) and size (13.5 to 15.5 mm) on day 11 of the menstrual cycle, which resulted in a higher number of MII oocytes (2.6 to 4.2), and an increase in number of blastocysts (0 to 3) and endometrial thickness (8.6 to 9.4). Regarding the Amenorrhea group, a reboot in menstrual cycle was observed, although no further development of blastocyst was found. Conclusion The AD-MSCs inyection directly in the ovary allowed an increase in number of blastocysts and improved pregnancy rates in POI/OA patients.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report

Feb 2021 DOI 10.14302/issn.2372-6601.jhor-21-3733
Qing XinCorresponding author Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.

Cell Therapy as an Alternative approach for COVID-19 Infection Consequences: A Non-Systematic Review

Jan 2021 DOI 10.14302/issn.2692-1537.ijcv-20-3685
Elkhenany HodaCorresponding author Department of Surgery, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.

The current uncontrollable outbreak of novel coronavirus (COVID-19) has unleashed severe global consequences in all aspects of life and society, bringing the whole world to a complete halt and has modeled significant threats to the global economy. The COVID-19 infection manifests with flu-like symptoms such as cough, cold, and fever resulting in acute respiratory distress syndrome (ARDS), lung dysfunction, and other systemic complications in critical patients are creating panic across the globe. However, the licensed vaccine has started to show up; some resulted in side effects that would limit its possibility in some circumstances as allergic personnel, for example. Moreover, the production and approval of new drugs is a very complicated process and takes a long time. On the other hand, stem cells have gone the extra mile and intensively investigated at preclinical and clinical studies in various degenerative diseases, including infectious ones. Stem cells are proposed as a broad-spectrum therapeutic agent, which may suppress the exaggerated immune response and promote endogenous repair by enhancing COVID-19 infected lung microenvironment. Also, stem cells have different application manners, either direct transplantation, exosome transplantation, or drug delivery of specific cytokines or nanoparticles with antiviral property by engineering stem cells. This review discusses and summarizes the possible emerging role of cell-based therapy, especially stem cell therapy, as an alternative promising therapeutic option for the treatment and control of novel COVID-19 and its potential role in tissue rejuvenation after COVID-19 infection.

RETRACTED: Non-Surgical Removal of Basal Cell Carcinoma by Apis Mellifera L Venom

Dec 2020
Ahmed Kamal SamiaCorresponding author Ph.D. ARC, Egypt.

This article has been retracted on March 01, 2021. VIEW THE RETRACTION NOTICE (https://openaccesspub.org/jsce/article/2243) Background Apis Mellifera L venom (Honeybees) is potent and safe anticancer drug. The present case is Basal Cell Carcinoma (SBCC), recurrent and invasde the skin of head (upper right, in front of the right ear). The patient was 65 years old in time of first intervention and the origin of BCC was primarily seen as abnormal growths and changes in birth mole on right side of head. Materials & Methods Preparation Bee Venom solution: Bee venom powder (crude) of dose 1gm was dissolved in 1000 ml of sterile distilled water then filtered by 0.22 micron syring filter. That final concentration of the stock bee venom become 1 ug /ml (i.e. 1ul=1 ug), and kept at -20◦C. (1mg (dried BV) + 1ml (water) = Final concentration (1ug/1 ul)). Before this novel intervention, allergy test performed by subcutaneous injection of small dose of bee venom (0.1 ml) and wait for at least one hour. The patient was not hypersensitive to honeybees’ venom. First stage of treatment: 1- Syringe of 1ml volume was used for direct local injection of cancer area by 0.3 ml from prepared Honeybees venom (0.1 % conc.). 2- At the same time, subcutaneous injection of 0.5 ml of bee venom solution infiltrated around the affected ear. 3- Topical application of the bee venom ointment 2% (bee venom in Vaseline) inside affected ear to protect the ear drum. This process repeated daily with cleaning of the ear every time by suitable safe and sterile saline solutions. 2nd stage: daily S/C injection in axillary area upper lymph nodes of 0.3 ml / bee venom ‘total doses 0.6 ml BV’ (left & right). 3rd stage: bee venom dissolved in sterile Clove oil was applied on inner ear above the drum. 4th stage: Management of healing process was enhanced by ascorbic acid solution as topical application on dead cancer cells and to help in removal of exudates and debris. Results The complete removal of malignant growths in affected ear achieved after 1 month from first bee venom injections. However; the cancerous areas under the second surgical intervention were treated during the next month. Conclusions Apis Mellifera L venom as anticancer drug is totally different from using direct stings as a method of Apitherapy, that because collection of bee venom lead to evaporating of most allergic substance that present in bees stings, also it can be used per os in people who exhibit different degrees of allergy against the drug safely.

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.

NNC55-0396 Reduces SH-SY5Y Cell Damage Induced by Bupivacaine Hydrochloride

Aug 2020 DOI 10.14302/issn.2641-7669.ject-20-3529
Wen XianjieCorresponding author Department of Anesthesiology, the Second People`s Hospital of Foshan City, Foshan, Guangdong Province, China.

Background Local anesthetic neurotoxicity is a common complication in clinical anesthesia, which can cause permanent nerve damage in severe cases. The T-type calcium channel is an important channel for regulating the excitability of neurons. Normally, extracellular calcium ions enter the cell through the T-type calcium channel to change the excitability of neurons. When the intracellular calcium is overloaded, it can cause cell damage. Aims To investigated the roles of T-type calcium channel in the SH-SY5Y cells injury induced by the bupivacaine. Methods The SH-SY5Y cell culture model was used to observe the effect of T-type calcium channel blocker NNC55-0396 on the neurotoxicity of bupivacaine hydrochloride by MTT methold,flow cytometry, Western blotting and other methods. Results The results show that NNC55-0396 can block the T-type calcium channel of SH-SY5Y cells, improve the decrease of cell viability caused by bupivacaine hydrochloride, reduce the level of intracellular calcium ion, reduce the expression of Cleavedcaspase-3, and reduce cell apoptosis. Conclusion The above results indicate that the T-type calcium channel is involved in the SH-SY5Y cell damage caused by bupivacaine hydrochloride, and blocking the T-type calcium channel can reduce the neurotoxicity of bupivacaine hydrochloride.

Veterinary Healthcare Open Access

Investigation of Neoplastic Cells in the Bone Marrow of Female Dogs with Mammary Gland Tumors

Jul 2020 DOI 10.14302/issn.2575-1212.jvhc-20-3434
R.R. Moreira PamelaCorresponding author

Background The mammary glands are the second most common tumor development site in female dogs. One of the ways of staging such tumors is to evaluate the presence or absence of distant metastasis, including in bone marrow. Such findings in human medicine are associated with poor survival of women with breast tumors. However, in veterinary medicine, this clinical staging is used more for patients with lymphomas and mastocytomas. Studies using bone marrow biopsies as a staging method for mammary tumors are scarce. Objectives The present study was to evaluate mammary lesions and bone marrow in 23 female dogs, searching for disseminated tumor cells or metastatic foci. Results: Grade I carcinoma in mixed tumors was the type most observed (22.4%), and there was no statistical difference in relation to tumor size or presence of metastasis in lymph nodes. In the bone marrow of one female dog with carcinosarcoma (4.35%), there was cytoplasmic marking of a probable disseminated tumor cell of epithelial origin, and immunohistochemical evaluation showed presence of cytokeratin-19 antibodies. None of the female dogs presenting reduced cellularity or medullary fibrosis, confirmed through Masson’s trichrome technique, had cell marking in immunohistochemical analyses. Conclusions Bone marrow evaluation can be used as a staging method for mammary gland tumors in female dogs, since disseminated tumor cells present the potential to become secondary lesions and to disseminate to distant foci, thereby causing tertiary metastases over an indeterminate period of time.

Differential of Antioxidant Ability, CD4+T Cells Count and Viral Load in HIV Infected Patients on cART in Yaounde, Cameroon

Jun 2020 DOI 10.14302/issn.2691-8862.jvat-20-3417
Teto GeorgesCorresponding author Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon

Background Decreased antioxidant ability is one of the worsening conditions in AIDS.We aimed to evaluate total antioxidant ability among others, and their variation in HIV infected patients following their CD4+T cells count and viral load, in a context of new ART scarcity in most LMICs. Material and Methods We conducted a cross sectional study on 167 individuals (76 controls, 33 treatments naïve and 58 HIV-1 infected patients on ART). We assessed their plasma total antioxidant ability (FRAP), malondialdehyde (MDA) and thiol (SH) groups using standard spectrophotometric methods, then we calculated lipid peroxidation index (LPI). Statistical analysis was performed using GraphPad Prism 6. Data were analyzed by two-tailed unpaired t-test for two groups’ comparison and ANOVA for more than two groups. Pearson correlation between CD4+T cells count, viral load and the above markers was determined; P ≤ 0.05 was considered statistically significant. Results The following controls/naïve/treated subjects’ values for FRAP(mM) (1.907±0.074/1.77±0.05/1.695±0.03); MDA(μΜ) (0.781±0.081/1.115±0.118/ 1.342±0.109); SH (μΜ) (2.747±0.130/1.582±0.197/1.498 ±0.140)and LPI (0.43±0.61/ 0.61±0.7/2.59±0.83) were all obtained with P ≤ 0.05. The FRAP increased only with 3TC+TDF+EFV and 3TC+ABC+NVP cART while MDA decrease significantly with the later(p=0.027). MDA and LPI significantly increased in heavily treated patients with p<0.0014 and p=0.0001 respectively. overall, the patients showed an increase of viral loads following a decrease of CD4+T cells (r= -0.803, p=0.016) but 3TC+TDF+EFV seem to better manage the both. The only significant correlation was established between SH groups and CD4+Tcells count (r=0.447; p=0.0006); Conclusion Our study showed that thiol groups may be protective againstCD4+Tcells count depletion and that the cART 3TC+TDF+EFV, 3TC+ABC+NVP may be helpful in fighting against free radical generation and particularly 3TC+TDF+EFV as controlling CD4+Tcells count and viral load in long term treated patients. The study particularly showed the implication of cART in increasing lipid peroxidation index following the treatment duration in heavily treated patients, which aggravated their conditions in an area where drug options are limited, calling for new drugs availability and personalized medicine.

Invivo Impact of Malaria and HIV Co-Infection on CD4 Cell Count of Infected Patients of Niger Delta Extraction

May 2020 DOI 10.14302/issn.2328-0182.japst-20-3347
Obioma AzuonwuCorresponding author Department of Medical Laboratory Science, Medical Bacteriology / Virology / Parasitology Unit, Rivers State University, Nkpolu – Oroworukwo, Port Harcourt, Rivers State, Nigeria.

The study evaluated the impact of co-infection of malaria parasitaemia, and HIV positive indices on the CD4 cell count of 120 HIV infected subjects, who were already diagnosed and visiting Braithwaite Memorial Specialist Hospital Port Harcourt for routine Medical check-up. Also, a control group of 40 HIV negative were included as part of the study control group. The subjects were between the age ranges of ≤10–79 years respectively. A double check laboratory assay was conducted to detect the presence of antibody to HIV as confirmed using immunocomb 11 and Determine for HIV status. A thick Blood film stained with field stain (A and B) was used to detect the presence of malaria parasite in the subject’s blood. Furthermore, CD4 cell count was assayed using Partec cyflow counter (Partec, Germany). Excel and Graphpad statistical software were used for analysis of the data generated. The result among the HIV positive subjects and control subjects revealed that the highest positive for malaria infection was observed among ≤10 years age group as 2 (100%) and 11 (84.61%) respectively. In the HIV positive subjects, the distribution of malaria infection among sex revealed a high rate in male 42(77.78%) than in female 44 (66.67%). Similarly, the control recorded a high rate of malaria infection in male 11 (57.89%) than in female 7 (33.33%). However, 86 (71.67%) had malaria and HIV co-infection while 34 (65%) had only HIV mono infection. The positive HIV subjects who had CD4 cells count below 200 cells/mm3 were 15%, above 200-499cells/mm3 were 58.3% while 500 cells/mm3 and above had normal CD4 cells counts for 26%. Nonetheless, for the control subjects, no CD4 cells count of below 200cells/ mm was observed, 2.5% fell within the moderate category while 75% had normal CD4 cells count. Statistical analysis using ANOVA and t-test showed that there is significant difference between CD4 of seropositive and seronegative subjects infected with or without malaria (p=0.00). In addition, a t-test further demonstrated Comparison of Mean CD4 Cell Count among HIV and Malaria Infected and Non-Infected Subjects. MP/HIV Co-Infection and Mono Infection with No Infection showed strong mean difference (p=0.00) in the various CD4 counts while HIV Mono-Infection and others only had a non significant (p=0.44) mean difference between HIV Mono-Infection and No HIV or Malaria Infection. A robust and effective malaria and HIV control management programme should be strongly underpinned; so as to improve the quality of life of patients and HIV patients should be encouraged to live a healthy life style, through the provision of antiretroviral drugs and regular health education engagement, even as the provision of antimalarial treated net would be helpful to the subjects.

Quantitative Computational Prediction of the Consensus B-cell Epitopes of 2019-nCoV

Apr 2020 DOI 10.14302/issn.2691-8862.jvat-20-3278
Isea RaúlCorresponding author Fundación Instituto de Estudios Avanzados, Hoyo de la Puerta, Baruta. Venezuela.

The goal of this paper is to obtain the numerical consensus of B cell epitopes from the three-dimensional structure of the prefusion spike glycoprotein of the new betacoronavirus that could lead to the development of a vaccine to 2019-nCoV. In order to do that, we first calculated the B-cell epitopes that are predicted using fourteen different mathematical algorithms. Later, we obtained the consensus of B-cell epitopes according to the Similarity Index, and finally selecting the best candidates according to the results of a function called <F> which is evaluated for the glycoprotein. The best candidates that we obtained in order to design a vaccine are SSANNCT, PLQSYGFQPT, TESNKKFLP, NNSYEC, AENS, LPDPSK and YDPLQPE.

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

RETRACTED: Assessment of the Risk of Hemochromatosis in Polytransfused Sickle Cell Patients at the Abidjan Transfusion Therapy Unit

Apr 2020 DOI 10.14302/issn.2372-6601.jhor-20-3189
Mamadou Sekongo YassonguiCorresponding author Department of Training and Research, National Blood Transfusion Center; Abidjan; Côte D’Ivoire

This article has been retracted on 29 January 2021. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2372-6601.jhor-25-5854) In Côte d'Ivoire, sickle cell disease affects 14% of the population. It is responsible for significant morbidity and mortality. Transfusion is a significant element in the management of major sickle cell anemia, which exposes them to post-transfusion hemochromatosis. The biological diagnosis is based on the determination of serum iron and the transferrin saturation coefficient (CST). As the determination of the CST was not available in our exercise context in Côte d'Ivoire, we determined only the ferritinemia. The interest of this work lies in the therapeutic implication linked to the identification of patients at risk of hemochromatosis because chelators are difficult to access for most patients. This was a prospective, descriptive and analytical study, on polytransfused sickle cell patients, followed at the transfusion therapy unit (UTT) of the CNTS of Abidjan, from 2010 to 2018. We included 78 sickle cell patients, all ages and genders who have received at least ten transfusions. The ferritinemia assay was carried out by ELISA. Transfusion exchange, with 59% of cases, was the most used mode of transfusion. The mean ferritinemia was 1719.19 ng / ml. Hyperferritinemia was found in 63% of patients. Most of the patients were on a long-term transfusion program with an average of 27.5 bags of red blood cell concentrates. Thirty-two patients had received at least 20 bags of red blood cell concentrates. We noted 21 patients treated, including 3 with deferoxamine and 18 treated with oral deferasirox. We have identified 33 sickle cell anemia patients at risk for hemochromatosis. The determinants of the risk of hemochromatosis were the high number of blood bags and the method of transfusion.

Structural Equation Modeling to Detect Predictors of CD4 Cell Count Change due to Long Term Antiretroviral Therapy Administered to HIV-Positive Adults at Felege Hiwot Teaching and Specialized Hospital, Bahir Dar, Ethiopia

Mar 2020 DOI 10.14302/issn.2641-4538.jphi-19-2610
Seyoum Tegegne AwokeCorresponding author Dept. of statistics, Bahir Dar University, Ethiopia

Background The relationship between predictors and the variable of interest was estimated using a structural equation model which is used to predict latent variables. The main advantage of the SEM is the ability to estimate the direct and indirect pathways of the effect of the primary independent variable on the outcome, given sufficient sample sizes. Despite not directly modeling the mediated pathways, GLMMs excluding mediating variables performed well with respect to power, bias and coverage probability in modeling the total effect of the primary independent variables on the outcome. In longitudinal studies, data are collected from subjects at several time points. The main purpose of longitudinal analysis is to detecting the trends or trajectories of the variables of interest. Methods A longitudinal study was conducted on 792 adults living with HIV/AIDS who commenced HAART. Structural equation modeling was used to construct a model to detecting predictors of CD4 cell count change. The procedure was illustrated by applying it to longitudinal health-related quality-of-life data on HIV/AIDS patients, collected from September 2008 to August 2012 monthly for the first six months and quarterly for remaining study period. Results The result of current investigation indicates that CD4 cell count change was highly influenced by certain socio-demographic and clinical variables. Out of all the participants, 141 (82%) have been considered 100% adherent to antiretroviral therapy. Structural equation modeling has confirmed the direct effect that personality (decision-making and tolerance of frustration) has on motives to behave, or act accordingly, which was in turn directly related to medication adherence behaviors. In addition, these behaviors have had a direct and significant effect on viral load, as well as an indirect effect on CD4 cell count. The final model demonstrates the congruence between theory and data (x2/df. = 1.480, goodness of fit index = 0.97, adjusted goodness of fit index = 0.94, comparative fit index = 0.98, root mean square error of approximation = 0.05), accounting for 55.7% of the variance. Conclusions The results of this study support our theoretical model as a conceptual framework for the prediction of medication adherence behaviors in persons living with HIV/AIDS. Implications for designing, implementing, and evaluating intervention programs based on the model are to be discussed.

Pure Small Cell Carcinoma of Prostate in a Patient Presenting with Acute Urinary Retention: A Rare Case Report

Feb 2020 DOI 10.14302/issn.2641-5518.jcci-20-3217
Ozcelik FatihCorresponding author University of Health Sciences, Sultan 2. Abdulhamid Han Training and Research Hospital, Department of Medical Biochemistry, Istanbul, Turkey

Small cell carcinoma of the prostate is a rare and highly aggressive subtype of prostate cancers. In this case report, we evaluated a patient applied our outpatient clinic with acute urinary retention, whose pathology reported as pure small cell carcinoma of the prostate. A 73-year-old male patient was admitted to our outpatient clinic with acute urinary retention. Digital rectal examination was normal. The PSA value was 1.81 ng/dl. Prostate size was 101 cc. Open prostatectomy was performed. The pathology of the patient was reported as pure small cell prostate carcinoma. Four cycles of etoposide and cisplatin chemotherapy were administered to the patient. The patient died 13 months later after the first diagnosis. We evaluated the pathological and clinical findings of small cell carcinoma of the prostate.

Energy Conservation Open Access

The Fermi-Pasta-Ulam Quantum Recurrence in The Dynamics of an Elementary Physical Vacuum Cell and The Problem of its Polarization

Feb 2020 DOI 10.14302/issn.2642-3146.jec-20-3179
A. A Berezin.Corresponding author Independent researcher, Moscow, Russia

A model of a Quantum recurrence in the dynamics of an elementary physical vacuum cell within the framework of four coupled Shrodinger equations has been suggested. The model of an elementary vacuum cell shows that a Quantum recurrence which represents the dynamics of virtual transformations in the cell, qualitatively differs from that of Poincare and the Fermi-Pasta-Ulam. Whereas these recurrences develop in time or space, the Quantum recurrence develops in a sequence of Fourier images represented by non exponentially separating functions. The sequence experiences random energy additions but no exponential separation occurs. The Quantum recurrence can be defined as the most frequent array of Fourier images that appear in a certain quantum system during a period of its observation. Different scenarios of the Fourier images sequences interpreted as bosons (electron and positron) and fermions (photons) apearing in the solutions of the model demonstrate that during some periods of its observation they become indistinguishable. The quantum dynamics of every physical vacuum cell depends on the dynamics of many other vacuum cells interacting with it, thus the quasi periodicity (during the period of observation) of the Fourier images recurrence can have infinite periods of time and space and the amplitudes of the Fourier images can vary many orders in their magnitudes. Such recurrence times does not correspond even roughly to the Poincare recurrence time of an isolated macroscopic system. It reminds the behavior of spatially coupled standard mappings with different parameters. The amount of energy in the physical vacuum is infinite but extracting a part of it and converting, it into a time-space form requires a process of periodical transfer of the reversible microscopic system dynamics into that of a macroscopic system. This process can be realized through a resonant interaction between the classical and quantum recurrences developing in these two systems. However, a technical realization of this problem is problematic.

Monitoring Mast Cell Populations in Waldenström’s Macroglobulinemia: A Xenotransplantation Study

Dec 2019 DOI 10.14302/issn.2372-6601.jhor-19-3092
S. Tsingotjidou AnastasiaCorresponding author Laboratory of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GR-541 24, Greece

Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized mainly by uncontrolled accrual of M- immunoglobulin, secreted by malignant lymphoplasmatic cells. Mast cells interacting with malignant B-cells play an important role at the manifestation of the disease. Utilizing a previous xenotransplantation mouse model, this study evaluates long-term implant viability and quantifies distinct bone marrow mast cell populations along with their dynamics in non-WM and WM human bone implants. Non-WM bone implants were obtained from the femoral head of adult humans undergoing hip arthroplasty or hemiarthroplasty, whereas WM human bone implants originated from bone biopsies obtained from the posterior iliac crest of patients with active WM. All bone particles were implanted intramuscularly in twenty-four NOD/SCID mice. Following 3, 4 or 8 months postoperatively, xenografts were removed and studied using special histological techniques to identify mature and immature mast cells. Xenografts survived up to 8 months after implantation presenting normal cytoarchitecture (non-WM) or high-grade neoplastic infiltration and microresorption (WM bone biopsies). Statistical analysis of mast cell populations showed significant elevation regarding time progression and bone marrow microenvironment, thus suggesting the possible influence of malignant cells to the mast cell population in WM. This study presents the extended survival of intramuscular implantation of human adult bone xenografts into NOD/SCID mice and provides additional information on the interaction between mast cells and malignant B-cells.

Role of Tie2, CD14, Angiopoietin as Angiogenetic Markers in Hepatocellular Carcinoma Complicating Hepatitis C Virus Infection

Nov 2019 DOI 10.14302/issn.2372-6601.jhor-19-3084
Elyamany AshrafCorresponding author Ass. Professor of Medical Oncology, SECI, Assiut University, Egypt.

Background Identifying biomarkers for early detection of hepatocellular carcinoma (HCC) remains quite challenging. In this study we aimed to estimate the number of TIE2-expressing monocytes (TEMs) cells, which display pro-tumoral activities and are defined as CD14+, TIE2+, and angiopoietin-2; and its potential use as a possible diagnostic marker in HCC patients complicating HCV induced cirrhosis. Methods Current study was conducted on 112 patients. They were divided into two groups: Group I (78 patients) with HCC complicating HCV induced cirrhosis; and group II chronic hepatitis C patients (34 patients). Both groups were compared to (age and sex-matched) healthy persons as group III (38 persons). Result The number of the circulating TEMs: CD14+ and TIE2+ monocytes were significantly higher in the peripheral blood of HCC patients than HCV LC patients and healthy controls, sensitivity and specificity for HCC diagnosis were respectively: CD14 (89.7%, 83.3%), TIE 2 (76.9%, 83.3%), and Ang-2 (76.9%, 66.7%). Moreover, analysis of the P-value and the odd’s ratio showed that CD14 has the highest predictive value for HCC. Conclusion Our results suggest that TEMs and Ang-2can be used as diagnostic markers for HCC, especially among the high-risk group of patients.

Energy Conservation Open Access

Perspectives on Sub–Nanometer Level of Electronic Structure of the Synchrotron with Mendelevium Nanoparticles for Elimination of Human Cancer Cells, Tissues and Tumors Treatment Using Mathematica 12.0

Nov 2019 DOI 10.14302/issn.2642-3146.jec-19-3072
Heidari AlirezaCorresponding author Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA

Mendelevium nanoparticles absorb energy of descendent light and generate some heat in the particle. The generated heat transferred to the surrounding environment and leads to increase in temperature of adjacent points to nanoparticles. Heat variations can be obtained by heat transfer equation. In the current study, thermoplasmonic characteristics of Mendelevium nanoparticles with spherical, core–shell and rod shapes are investigated. In order to investigate these characteristics, interaction of synchrotron radiation emission as a function of the beam energy and Mendelevium nanoparticles were simulated using 3D finite element method. Firstly, absorption and extinction cross sections were calculated. Then, increases in temperature due to synchrotron radiation emission as a function of the beam energy absorption were calculated in Mendelevium nanoparticles by solving heat equation. The obtained results show that Mendelevium nanorods are more appropriate option for using in optothermal human cancer cells, tissues and tumors treatment method. When Mendelevium nanoparticles are subjected to descendent light, a part of light scattered (emission process) and the other part absorbed (non–emission process). The amount of energy dissipation in non–emission process mainly depends on material and volume of nanoparticles and it can be identified by absorption cross section. At the other hand, emission process which its characteristics are depend on volume, shape and surface characteristics of nanoparticles explains by scattering cross section. Sum of absorption and scattering processes which lead to light dissipation is called extinction cross section. 

Human Health Research Open Access

In Vitro Cell-Based Biomarkers Study of Vital Organs: Impact of the Biofield Energy Based Test Formulation

Jul 2019 DOI 10.14302/issn.2576-9383.jhhr-19-2945
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), India

The present study was undertaken to evaluate the impact of Biofield Energy Treated test formulation using multiple cell-lines. The test formulation and cell media (Med) was divided into two parts; one part was untreated (UT) and other part received Biofield Energy Treatment remotely by a renowned Biofield Energy Healer, Krista Joanne Callas, USA and labeled as Biofield Energy Treated (BT) test item (TI)/Med. Based on cell viability, test formulation was found safe. Cytoprotective action of test formulation showed significant restoration of cell viability by 89.9% and 106.4% in human cardiac fibroblasts cells (HCF) cells, while improved restoration of cell viability by 77.3% and 69% in HepG2 cells compared to untreated. Cellular restoration in A549 cells was also improved by 141.2% and 157.1% compared to untreated. ALP activity was significantly increased by 118.7% and 140.7% in UT-Med + BT-TI and BT-Med + UT-TI, respectively at 0.1 µg/mL than untreated. Percent cellular protection of HCF (heart) cells (decreased of LDH activity) was significantly increased by 89.9% and 106.4% in UT-Med + BT-TI and BT-Med + BT-TI, respectively than untreated. HepG2 cells protection (decreased ALT activity) was increased by 59.8% in BT-Med + BT-TI than untreated. Superoxide dismutase (SOD) level was increased by 22.8% in BT-Med + BT-TI than untreated. Serotonin level was significantly increased by 361.7% and 197.6% in BT-Med + UT-TI and BT-Med + BT-TI, respectively than untreated in human neuroblastoma cells (SH-SY5Y). However, relative quantification (RQ) of vitamin D receptor (VDR) was significantly increased by 116.5%, 214.7%, and 241.5% in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively than untreated in MG-63 cells. Overall, data showed a significant improvement of organ-specific functional enzyme biomarkers. Thus, Biofield Energy Treated Test formulation (the Trivedi Effect®) would be useful for multiple organs health that can be beneficial against coronary artery disease, arrhythmias, congenital heart disease, cardiomyopathy, cirrhosis, liver cancer, hemochromatosis, asthma, chronic bronchitis, cystic fibrosis, osteoporosis, etc.

Impact of Biofield Energy Treatment Based Test Formulation on Vital Organ Health Specific Biomarkers Using Cell Line Study

Jul 2019 DOI 10.14302/issn.2640-6403.jtrr-19-2946
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), India

Multiple organ dysfunction syndrome or failure is one of the major concerns against healthcare services in order to maintain the normal function. The present study aimed to explore the impact of the Biofield Energy Treated test formulation on the function of vital organs such as bones, heart, liver, lungs, and brain using standard activity parameters in specific cell-based assays. The test formulation and cells medium was divided into two parts, one untreated (UT) and other part received the Biofield Energy Treatment remotely by a renowned Biofield Energy Healer, Ariadne Esmene Afaganis, Canada and was labeled as the Biofield Treated (BT) test formulation/media. The test formulation was tested for cell viability, and the data suggested that the test formulation was found safe and non-toxic against all the cell lines. Cytoprotective activity among the experimental groups showed a significant improved activity by 94.4% at 1 µg/mL in untreated medium (UT-Med) + Biofield Treated Test Item (BT-TI) group in human cardiac fibroblasts cells (HCF) cells, while 84.4% at 10 µg/mL in BT-Med + BT-TI groups in human hepatoma cells (HepG2), and 124% increased cytoprotective action at 1 µg/mL in UT-Med + BT-TI group in adenocarcinomic human alveolar basal epithelial cells (A549) cells as compared with the untreated test group. ALP activity in MG-63 cells was significantly increased by 85.9% at 10 µg/mL in the UT-Med + BT-TI group, while in Ishikawa cells showed maximum increased ALP activity by 59.2% at 0.1 µg/mL in BT-Med + BT-TI groups as compared to the untreated group. The percent protection of HCF (heart) cells (decreased of LDH activity) was significantly increased by 53% and 40.5% at 1 and 10 µg/mL concentrations respectively, in UT-Med + BT-TI group, while BT-Med + UT-TI group showed increased protection by 68.5%, 70.7%, and 16.8% at 0.1, 1, and 10 µg/mL respectively, and 86.5%, 62.5%, and 34.2% improved cellular protection at 0.1, 1, and 10 µg/mL respectively, in BT-Med + BT-TI group as compared to the untreated test group. The percent protection of HepG2 (liver) cells (decreased of ALT activity) was reported by 33.5%, 63.2%, and 99.2% at 10 µg/mL in the UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI groups, respectively compared to the untreated group. Cellular protection of A549 (lungs) cells (increased of SOD activity) in terms of percentage was increased by increased by 39.8% (at 10 µg/mL), 44% (at 25.5 µg/mL), and 59.7% (at 25.5 µg/mL) in the UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI groups, respectively compared to untreated group. Serotonin level was significantly increased by 59.2% (at 0.1 µg/mL), 190.3% (at 0.1 µg/mL), and 201% (at 1 µg/mL) in the UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI groups, respectively compared to untreated in human neuroblastoma cells (SH-SY5Y). However, the relative quantification (RQ) of vitamin D receptor (VDR) was significantly increased by 159.1% (at 50 µg/mL), 212.7% (at 1 µg/mL), and 278.3% (at 10 µg/mL) in the UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI groups, respectively as compared to the untreated in MG-63 cells. Thus, the present data concluded that the overall multiple organ health using various standard biomarkers in specific cell lines were significantly improved with respect to health of bones, heart, liver, lungs, and brain after treatment with the Biofield Energy treated test formulation (The Trivedi Effect®). Thus, it can be used as a complementary and alternative therapy approach against many multiple organ disorders such as coronary artery disease, arrhythmias, congenital heart disease, cardiomyopathy, cirrhosis, liver cancer, hemochromatosis, asthma, chronic bronchitis, cystic fibrosis, osteoporosis, etc.

Cell-Based Vital Organs Specific Biomarkers Assessment using Biofield Energy Based Novel Test Formulation

Jul 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2944
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), India

The aim of the present study was to determine the impact of Biofield Energy Treated test formulation using six differentcell-lines. The test formulation/item (TI) and cell media (Med) was divided into two parts; one part was untreated (UT) and other part received Biofield Energy Treatment remotely by a renowned Biofield Energy Healer, Janice Patricia Kinney, USA and labeled as Biofield Energy Treated (BT) test item (TI)/media. Based on cell viability assay, test formulation was found as safe at tested concentrations. Cytoprotective activity of test formulation showed a significant restoration of cell viability by 60.6% (10 µg/mL), 67.5% (63.75 µg/mL), and 117.5% (63.75 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, BT-Med + BT-TI, respectively compared to untreated in human cardiac fibroblasts cells (HCF) cells. Moreover, restoration of cell viability was improved by 64% and 127.3% in UT-Med + BT-TI and BT-Med + UT-TI, respectively at 1 µg/mL compared to untreated in human liver cancer (HepG2) cells. Cellular restoration in A549 cells was improved by 314% and 112.3% at 1 µg/mL in BT-Med + UT-TI and BT-Med + BT-TI, respectively than untreated. ALP activity in Ishikawa cells was significantly increased by 175.5%, 547.2%, and 220.8% in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively at 0.1 µg/mL as compared to untreated. Additionally, in MG-63 cells showed increased ALP activity by 76.9%, 78.4%, and 79% in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively at 50 µg/mL compared to untreated. The percent cellular protection of HCF (heart) cells (decreased of LDH activity) was significantly increased by 60.6% (10 µg/mL), 67.5% (63.75 µg/mL), and 117.5% (63.75 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively as compared to untreated. An improved HepG2 cells protection (represents decreased ALT activity) by 115.1% (1 µg/mL), 42.5% (25.5 µg/mL), and 60.8% (10 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, BT-Med + BT-TI, respectively as compared to untreated. Percentage cellular protection of A549 (lungs) cells (represents increased of SOD activity) was significantly increased by 191.1% and 81.4% at 0.1 µg/mL in UT-Med + BT-TI and BT-Med + BT-TI, respectively as compared to untreated. Serotonin level was significantly increased by 31.8% (10 µg/mL) and 56.9% (25.5 µg/mL) in UT-Med + BT-TI and BT-Med + BT-TI, respectively compared to untreated in human neuroblastoma cells (SH-SY5Y). Relative quantification (RQ) of vitamin D receptor (VDR) was significantly increased by 304.3% (0.01 µg/mL), 128.4% (0.1 µg/mL), and 240% (0.1 µg/mL) in UT-Med + BT-TI, BT-Med + UT-TI, and BT-Med + BT-TI, respectively compared to untreated in MG-63 cells. Thus, Biofield Energy Treated test formulation (The Trivedi Effect®) significantly improved organ specific functional biomarkers and would be useful for multiple organs health related to coronary artery disease, arrhythmias, congenital heart disease, cardiomyopathy, cirrhosis, liver cancer, hemochromatosis, asthma, chronic bronchitis, cystic fibrosis, osteoporosis, etc.

Excellent Completion Rate of 8-Weeks Hepatitis C Treatment in Prison; Results of French National Study.

May 2019 DOI 10.14302/issn.2328-0182.japst-19-2738
BARON AuroreCorresponding author USMP Fleury Merogis, CH Sud Francilien

Rationale Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Prevalence of viral hepatitis C (HCV) is higher in prison environment in France than in the general population and is estimated to be 4,8%. The impact in prison environment is little-known as based on local studies.  Inmate health care falls under USMP (prison setting medical unit), hospital specific units as by the january 18, 1994 law. Access to antiviral c treatment for inmates has always been difficult in France, would it be for interferon and ribavirin or use of protease inhibitors, with less than 20% of treated patients. French recommendations for HCV screening recommend systematic screening of inmates. The arrival of all oral therapies by direct antiviral agents (DAA) with shorter treatment times was an opportunity for doctors to propose a treatment and the patient to accept it. In 2014, the French guidelines recommended that HCV carriers in prison should systematically be treated independently of the stage of fibrosis. Objective of the Study PH8 Our objective was to evaluate the completion rate of an 8-week antiviral C treatment by sofosbuvir / ledipasvir regimen in non-cirrhotic genotype 1 patients in deprivation of liberty and achieve sustained virological response (SVR) and to measure the effectiveness of an 8-week treatment (by protocol analysis). Methodology prospective non-interventional multicenter trial among inmates with chronic hepatitis C genotype 1 with METAVIR fibrosis score F0 to F2 and who will receive a daily combination of sofosbuvir / ledipasvir for 8 weeks. Results 6 prison medical units included 115 consenting patients: there were 81% men, mean age 41 years (21 to 64 years). Route contamination was drug injection for 85%. HCV genotype was 1a for 74%, 1b for 24% and 2% none differenciated 1. Fibroscan mesure was available in 89 patients (mean score 3,5 KPa). Fibrotest was available in 37 patients with mean value 0.21. Eleven patients had Fibroscan and Fibrotest; 69% of patients were F0, 22% F1 and 9% F2. Average time between diagnosis and start of treatment was 3 weeks. We are sure that 109 patients (95%) completed DAA 8 weeks treatment; only 2 stopped DAA treatment before 8 weeks and 4 had no follow up after end of detention. HCV viral load was measured at W2 for 90 patients (78%), at W4 for 92 patients (78%), at end of treatment for 92 patients (78%), one month after treatment for 90 patients (78%) and 3 months after for 95 patients (93%). Only one viral load was positive, one month after treatment. Patient was retreated by sofosbuvir / velpastasvir. All HCV viral load 3 months after treatment negative; one patient took DAA only 6 weeks was cured. Conclusions In these study PH8, we observed completion rate of 94% for included patients in patient with 8 weeks ledipasvir/sofosbuvir regimen; data missed for only 4 patients and one relapsed. Short DAA treatment was efficient in prisoners and could be preferred in specific population.

Selective Cytotoxicity of Damsin Derivatives in Breast Cancer Cells

Apr 2019 DOI 10.14302/issn.2328-0182.japst-19-2759
Sterner OlovCorresponding author Centre for Analysis and Synthesis, Lund University, P.O.Box 124, 22100 Lund, Sweden

Cancer is the leading cause of death worldwide, and there is a constant need for new treatment strategies. Sesquiterpene lactones containing a 3-methylenedihydrofuran-2(3H)-one (or α-methylene-γ-lactone) moiety, for example damsin (1), are Michael acceptors that affect biological processes such as cell proliferation, death/apoptosis, and cell migration, by interfering with cell signalling pathways. Although the reactivity of the α-methylene-γ-lactone moiety is important for these effects, the Michael addition is reversible and it can be assumed that also other parts of the molecules will moderate any given biological activity. In this investigation, the cytotoxicity of 23 -methylene--lactones towards normal breast epithelial MCF-10A cells as well as breast cancer JIMT-1 cells is compared. Most of the investigated compounds are semisynthetic derivatives prepared by the condensation of the natural product damsin (1) with aldehydes. The two cell lines were treated with various concentrations of the compounds in dose response assays, and the 50 % inhibitory concentration (IC50) was determined from dose response curves. The IC50 values were found to depend strongly on the overall structure. The ratio between the IC50 values for MCF-10A and JIMT-1 cells, as a measure for the selectivity of a compound to kill cancer cells, was calculated, and found to vary between just over 1 to more than 10. The most potent derivatives formed from the condensation of 1 with aromatic aldehydes towards JIMT-1 cells are 3a and 3i, both with ratios between the IC50 values for MCF-10A and JIMT-1 cells close to 5. Also some aldol condensation products with acyclic aldehydes, i.e. 3r and 3u, were equally potent, and the latter showed the highest selectivity (ratio > 10). Structure-activity relationships that may explain the observed differences in potency and selectivity are discussed.

Zoological Research Open Access

Effect of Graded Levels of Spirulina (Arthropsira platensis) on Feed Intake and in vivo Digestibility of Trypsacum laxum in Guinea Pig (Cavia Porcellus L)

Apr 2019 DOI 10.14302/issn.2694-2275.jzr-19-2695
Miégoué EmileCorresponding author University of Dschang, Faculty of Agronomy and Agricultural Sciences, Department of Animal Production Animal Nutrition and production Research Unit B.P. 188 Dschang, Cameroun.

The intake and in vivo digestibility of Trypsacumlaxum in guinea pigs according to the graded level of spirulina was evaluated in Cameroon. 20 animals aged of 6 months with an average weight of 450 ± 50 g were randomly divided into 4 equivalent groups. Each group received T. laxum and 40g of compound feed containing 0% (TS0), 2% (TS2), 4% (TS4), and 6% (TS6) of spirulina. Feed intake was the different between the left over and the quantity served. The sample of T. laxum and those of each diet as well as feces were collected and analyzed for the apparent digestibility of each nutrient. Animals were weighed at the beginning and at the end of each period of the test to determine the body weight gain. This study showed that the average daily intake of dry matter (DM) for TS0, TS2, TS4 and TS6 was 74.39 ± 2.98, 78.66 ± 3.14, 83.89 ± 4.28 and 77.76 ± 4.40 g/head/day. The highest apparent digestibility coefficients of different nutrients were obtained with animals fed TS6 group while the lowest were observed in TS0.The apparent digestibility coefficient of dry matter (DM), organic matter (OM) and crude protein (CP) of the supplemented group were statistically higher than those of the control diet. Animals’ weight performances were statistically comparable between treatments. Thus, the combination of T. laxum with concentrated feed containing spirulina can be recommended for guinea-pigs, but the level of incorporation may not exceed 4% of its daily ration.

The use of Dermacell® in Fingertip Injury

Mar 2019 DOI 10.14302/issn.2641-5518.jcci-19-2626
Bertasi GiampietroCorresponding author University of Padua, Italy

Matrices or tissue scaffolds provide a collagen structure for tissue remodelling while the removal of viable cells aims to minimize or prevent inflammatory or immunogenic response. Allograft collagen scaffold can support the patient’s own cellular ingrowth, ingeneered to minimize an immune response and to yeld a bio-compatible matrix and support incoming cellular growth. The decellyularized dermis retains its growth factors, native collagen scaffold, and elastin, thanks to a LifeNet Health proprietaryprocessin technology.

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.

Chalkley Counting in Oral Tongue Squamous Cell Carcinoma:Does It have A Prognostic Value?

Mar 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2625
T Tan SweeCorresponding author Gillies McIndoe Research Institute, Wellington, New Zealand

Chalkley counting has been regarded as a relatively reliable method of quantifying tumor angiogenesis. In this study we investigated the reliability of Chalkley counting in quantifying tumor angiogenesis in oral tongue squamous cell carcinoma (OTSCC) using CD34; and tumor vasculogenesis using angiotensin converting enzyme, angiotensin II receptor 1 and angiotensin II receptor 2, in 32 OTSCC samples. Chalkley counting was performed by two independent observers. The averages of three ‘hot spot’ counts were compared with known prognostic factors. All four markers showed no correlation with any of the prognostic factors. When comparing the results from the two independent observers, the only marker shown to have a significant moderate correlation was CD34. The other three markers showed no significant correlation. The lack of statistical significance between the independent observers, and known prognostic factors with the four markers used, shows that Chalkley counting is not a reliable prognostic tool in OTSCC.

In vitro Assessment of the Biofield Treated Test Item on Cardiac Function Using Rat Cardiomyocytes Cell Line (H9c2) via Multiparametric Analysis

Feb 2019 DOI 10.14302/issn.2329-9487.jhc-19-2582
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), India

Introduction Heart disorders are the major concern of population health worldwide. According to WHO estimates 2018, 17.9 million peoples were died due to cardiovascular disorders. Aim The aim of this study was to investigate the cardioprotective activity of Biofield Energy Treated test item, Dulbecco's Modified Eagle Medium (DMEM) using rat cardiomyocytes (H9c2). Methods The test item (DMEM) was divided into three parts, first part received one-time Biofield Energy Treatment by a renowned Biofield Energy Healer, Mahendra Kumar Trivedi and was labeled as the one-time Biofield Energy Treated (BT-I) DMEM, while second part received the two-times Biofield Energy Treatment and is denoted as BT-II DMEM. The third part did not receive any treatment and defined as the untreated DMEM group. Results Cell viability of the test samples by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay showed 89.03% and 98.49% in the BT-I and BT-II groups, respectively suggested a nontoxic and safe in nature of the tested test item. The BT-I group showed 16.01% restoration of cell viability. The level of lactate dehydrogenase (LDH) was significantly inhibited by 50.37% and 49.35% in the BT-I and BT-II groups, respectively compared to the untreated DMEM group. Moreover, percent protection of creatine kinase-myocardial band (CK-MB) by 49.48% and 59.79% in the BT-I and BT-II groups, respectively, compared to the untreated DMEM group. Reactive oxygen species (ROS) level in terms of mean fluorescence unit (FU) was reduced by 6.64% in the BT-I group than untreated DMEM. Besides, BT-I and BT-II groups significantly increased the level of % apoptotic cells by 63.16% and 97.37% (p≤0.05), respectively than untreated DMEM. Conclusion Allover, results envisaged that Biofield Treatment significantly improved different cardiac parameters. Thus, Biofield Energy Treatment (The Trivedi Effect®) could be utilized as a cardio-protectant against several cardiac disorders such as coronary artery disease, heart attack, arrhythmias, heart failure, congenital heart disease, cardiomyopathy, etc.

Carbohydrates Open Access

Lignocellulosic Waste as a Sole Substrate for Production of Crude Cellulase from Bacillus subtilis PJK6 Under Solid State Fermentation Using Statistical Approach

Dec 2018
K. Bhardwaj NishiCorresponding author Joint Director, Avantha Centre for Industrial Research & Development, Paper Mill Campus, Yamuna Nagar – 135 001 (Haryana)

The agricultural organic wastes pose major environmental issues and their inappropriate disposal is a major cause of pollution while these as cheap lignocellulosic resources can be utilized for many value added products such as enzymes. The purpose of the present study was to utilize wheat bran as a sole substrate for enhanced cellulase production under submerged fermentation (SMF) or solid state fermentation (SSF) and optimize the various process variables involved in the selected fermentation type. In order to achieve high titer of cellulase, a central composite design (CCD) was constructed and performed for optimization of SSF with five process variables at five coded levels. A 25 full factorial design was constructed leading to a set of 50 experiments that were performed in triplicates. The key variables namely incubation time, temperature, wheat bran and tap water ratio, pH and inoculum size were evaluated. The optimization of the process variables resulted in 1.14 IU/ml of cellulase activity from Bacillus subtilis PJK6 under SSF using wheat bran as a sole organic substrate with tap water. The optimum conditions included incubation time- 72 h, temperature- 45oC, pH- 6, inoculum size- 14% with 1:4 as wheat bran and tap water ratio. The production of cellulase using only moistened wheat bran was demonstrated and found to be significantly controlled by incubation time and temperature while pH showed the least effect. The economic production of valuable and useful enzyme using agricultural residue was achieved at moderate conditions from a GRAS microbe that can benefit the industry as well as the environment.

Zoological Research Open Access

Physiological Features of Pennisetum Purpureum or Panicum Maximum Consumption in Guinea Pigs (Cavia Porcellus)

Dec 2018 DOI 10.14302/issn.2694-2275.jzr-18-2474
Emile MiégouéCorresponding author

Guinea pig diet is essentially based on the use of grasses associated with protein sources. Then, in to improve the herbivores nutrition, the evaluation of intake and In vivo digestibility of Pennisetum purpureum or Panicum maximum in guinea pigs (Cavia porcellus) was carried out in January 2017 at the University of Dschang research and experimental farm and animal production and nutrition laboratory. 20 adult animals of local breed on average weight 450 ± 50g and aged about 5 months were used. They were organized into two batches of 10 animals each (5 males and 5 females). The first batch received 250g of fresh matter of Pennisetum purpureum + 60g concentrate/animal/day, while the second received the same treatment with Panicum maximum as grasses. Leftover and animals were weighed every morning before food distributions, and drinking water containing vitamin C was served ad libitum. According to the results, the highest ingestion was obtained with Panicum maximum. However, the digestibility different nutrients was comparable between treatments; nevertheless, males fed on P. maximum digested crude cellulose (63.78%) better than males fed on P. purpureum (51.17%). With regard to the variation of the bacterial rate of the caecal flora, enterobacteria of animals fed P. maximum was high (11.20 CFU/ml) compared to those of the animals receiving P. purpureum (7.27 CFU/ml), although regardless of the treatment, the level of lactobacilli was higher than that of enterobacteria. In view of the results obtained, these grasses can be alternatively used in feeding guinea pigs.

Enhanced Alkaloid Production from Cell Culture System of Catharanthus roseus in Combined Effect of Nutrient Salts, Sucrose and Plant Growth Regulators

Dec 2018 DOI 10.14302/issn.2576-6694.jbbs-18-2475
Kumar Srivastava RajeshCorresponding author Department of Biotechnology, GITAM Institute of Technology, Gandhi Institute of Technology and Management, (GITAM) (Deemed to be University), Rushikonda, Visakhapatnam (A.P.), India.

Callus and biomass culture of Catharanthus roseus L. were established to check for the presence of total alkaloid and its subsequent yield. Various treatments like strength of nutrient salts, sucrose concentrations and combinations of plant growth regulators (PGR’s) were applied to both MS and B5 in agar as well as suspension medium to test their effects on enhanced alkaloid content and its yield. There was no significant difference in any of the observable parameters of fresh wt, dry wt, alkaloid content, production, productivity and yield if the culture were treated similarly in both types of media formulations (MS or B5 salts). Physical state (agar solidified or the liquid suspension) of the medium had significant effect on all the parameters particular on fresh wt, alkaloid content and yields. Although, the fresh wt. and dry wt. of biomass in suspension culture was 2-3 times less than that of callus obtained from agar medium. However, the alkaloid content and yield was 2-3 times higher in suspension culture compared to agar medium in similar treatments. The highest alkaloid content observed was 5.67mg/g dwt in B5 suspension medium containing 3% sucrose and modified with 0.5mg/l 2,4-Dichlorophenoxy acetic acid (2,4-D) + 1 mg/l Kinetin (KIN) + 2mg/l α- naphthalene acetic acid (NAA). The combined effects of these factors on the enhanced production of total alkaloids were expected to contain higher yield of anticancer vinblastine and vincristine in the cell suspension culture system.

In Vitro Assessment of Estrogenic Potential of Biofield Energy Treatment using Human Endometrial Adenocarcinoma Cell Line

Dec 2018 DOI 10.14302/issn.2381-862X.jwrh-18-2459
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd.,Bhopal, India

The objective of the study was to investigate the effect of Consciousness Energy Healing based DMEM medium on the level of alkaline phosphatase enzyme (ALP) activity in Ishikawa cells. The test item, DMEM medium was divided into two parts. One part of the test item received Consciousness Energy Healing Treatment by a renowned Biofield Energy Healer, Mahendra Kumar Trivedi and was labeled as the Biofield Energy Treated DMEM, while the other part did not receive any treatment, and defined as the untreated DMEM group. The cell viability using MTT assay of the Biofield Energy Treated DMEM group was observed as 108%, which indicated that the test item was safe and non-toxic. The estrogenic potential using ALP level showed a significantly increase by 73.21% in the Biofield Energy Treated DMEM group as compared to the untreated DMEM group. Overall, the experimental data suggested that the Biofield Energy Treated DMEM has significantly improved ALP level, which play a vital role for the promotion and maintenance of estrogen level. Based on the study outcomes, it is concluded that Biofield Energy Healing Treatment showed a significant improved ALP level, which can be used in various estrogenic disorders such as hypophosphatasia, osteoporosis, severe anemia, malnutrition, hypothyroidism, magnesium deficiency, heart surgery, aplastic anemia, chronic myelogenous leukemia, enteritis in children, Wilson’s disease, pernicious anemia, bacterial infection and intrauterine infection is a leading cause of pelvic inflammatory disease, subfertility, infertility, endometritis, early pregnancy loss, fetal defects, and preterm birth.

Effect of Bone Marrow and Adipose Mesenchymal Stem Cells on Rat Intestinal Injury Induced by Methotrexate

Nov 2018 DOI 10.14302/issn.2640-6403.jtrr-18-2449
Mohammad F EbtehalCorresponding author Pharmacology Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury.

The Anemone, The Porcupine: Hairy Cell Leukaemia

Nov 2018 DOI 10.14302/issn.2689-5773.jcdp-18-2435
Bajaj AnubhaCorresponding author Consultant Histopathologist

Theobjective of reviewing Hairy Cell Leukaemia may be achieved by emphasising the condition as a category of chronic lymphocytic leukaemia with hair like protrusions of the cytoplasm situated on the aberrant B cell surface. An infrequent disorder, hairy cell leukaemia contributes an estimated 2% of lymphoid malignancies with a male predominance ( M:F ::4-5:1). A majority (90%) of instances depict a mutant immunoglobulin heavy chain variable region (IGHV). The haematopoietic stem cells (HSCs) elucidate a B raf proto-oncogene( BRAF V600E gene- 7q34). An enlarged spleen may be discerned along with pancytopenia as a presenting symptom. The morphology of specific hairy cell leukaemia may be on account of an in vitro interaction of primary hairy cells with BRAF genes and MEK inhibitors, which incite a prominent MEK - ERK dephosphorylation, thereby curtailing transcriptional outpourings of the RAS- RAF- MEK-ERK pathway. Bone marrow aspiration or bone marrow trephine biopsy may be inadequate for diagnosis in 30%-50% individuals on account of extensive fibrosis and the bone marrow sections depict a characteristic interstitial infiltration of leukaemia cells.. Reticulin stains exhibit broad, dense reticulum fibres surrounding the individual or aggregates of leukaemia cells with fibrotic extensions into the abutting bone marrow. The immune reactivity of classic hairy cell leukaemia is concurrent CD19+ CD20+,CD 11c+, CD25+, CD103+ and CD123+. Immune staining for CD20+, annexin 1 and VE1 (a BRAF V600E stain) validates the diagnosis and analyses the extent of malignant bone marrow infiltration. Application of inhibitors of BRAF V600E gene is efficacious in patients resistant to standard therapy. An enlarged spleen beyond 3 centimetres of the left costal margin, a white blood cell count greater than 10000 cells/µL , circulating hairy cells in the peripheral blood greater than 5000 cells/µL and a β 2 micro-globulin level exceeding twice the normal range of 3 µg/ml delineate an inferior outcome with resistance to purine analogues (PNAs). CD38+ elucidation ensures a worse prognosis as does the lack of an IGHV mutation with a reduced overall survival,. A lack of BRAF genetic mutation in 10% -20% of hairy cell leukaemia comprises of inferior prognosis.

Evaluation of Blood Ordering Practice for Packed Red Blood Cells in A Tertiary Care Hospital

Oct 2018 DOI 10.14302/issn.3070-1937.ijbt-18-2410
PrasanthB KrishnaCorresponding author Epidemiologist & Assistant Professor, Department of Community Medicine, Ponnaiyah Ramajayam Institute of Medical Sciences.

Introduction: Blood is a valuable resource and blood transfusion is life saving in many situations. However blood transfusions carry the risk of transfusion transmitted infections, allergic reactions, hemolytic reactions and introduction of foreign antigens. So monitoring of blood transfusion practice is necessary for the rationale use of blood components. The aim of this study was to evaluate the appropriateness of blood ordering practice for Packed Red Blood Cells (PRBC) as per National Blood Transfusion Guidelines. Materials & Methods: The study was conducted in a tertiary care hospital in Tamilnadu. A total of 4236 blood request forms were analyzed over a period of 12 months. Number of units requested were noted and the appropriateness of the requested transfusion was assessed according to the National guidelines on transfusion 3. Request forms of neonates and children up to 18 years of age (in whom Transfusion guidelines are different) were excluded from the study. Cross match to Transfusion ratio (CT ratio) was also calculated. Results: A total of 4236 blood request forms were analyzed out of which 76.6 % (n=3246) were for PRBC, and hemoglobin values were mentioned in 68.8% (n=2235) and not mentioned in 31.2% (n=1011) of request forms. Anemia, surgery and bleeding were the most common indications for which transfusions were requested. There were 3246 PRBC requests out of which 53.5% (n=1736) requests were considered appropriate, 38.6% (n=1254) were considered inappropriate and 7.9% (n=256) requests could not be assessed due to inadequate details on Hemoglobin and clinical relevance. CT ratio was 1.5. Conclusion: In this study, it was noted that significant percentage (38.6%) of inappropriate PRBC transfusions were given and 7.9% forms could not be assessed due to inadequate investigation details. Regular audits and CMEs should be conducted in this hospital to rationalize the use of blood components.

Antioxidant Activity Open Access

Antioxidative Potential of Consciousness Energy Healing Treatment on HepG2 Cells and DMEM after Oxidative Stress Induced by Hydrogen Peroxide

Oct 2018 DOI 10.14302/issn.2471-2140.jaa-18-2400
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd.,Bhopal, India

Antioxidants can reduce oxidative stress in cells is used for the treatment of several disorders such as cancer, cardiovascular, and inflammatory diseases. The present study was evaluated the antioxidant potential of the Consciousness Energy Healing (The Trivedi Effect®) Treated human hepatoma cell line (HepG2) and Dulbecco's Modified Eagle Medium (DMEM) for the assessment of cell viability under hydrogen peroxide-induced oxidative stress. The Biofield Energy Treated HepG2 cells group was maintained for 23 days under standard conditions. On the next day, the cells were challenged with 1 mM of H2O2 for the generation of oxidative stress. The ability of the Biofield Energy Healing Treatment to protect from the oxidative stress was determined by MTT cell viability assay and compared with the negative control group. The percentage of cell viability was significantly (p≤0.001) increased by 13.6% in the Biofield Energy Treated DMEM group; while altered by 3.2% in the Biofield Energy Treated HepG2 cells group compared to the negative control groussp. Overall, the Biofield Energy Treated DMEM showed a better antioxidative protection against oxidative stress than HepG2 cells group, which was induced by H2O2. Therefore, the results envisaged that The Trivedi Effect®- Biofield Energy Healing Treatment has an impact on the protection of various vital organs from oxidative stress; which might be helpful in the development of powerful/energized growth medium for the accelerated study with a cost-effective manner.

Perioperative Period is a Critical Gap for Minimal Residual Cancer Cells Progression and Therapy: Biological and Molecular Based Evidences

Oct 2018 DOI 10.14302/issn.2372-6601.jhor-18-2396
Tawfik Amin AnwarCorresponding author Surgical Oncology Department, South Egypt Cancer Institute Assiut University, Egypt.

Although surgery is the main treatment for solid tumors, it could enhance the growth and metastasis of minimal residual cancer. In this review article we have discussed the perioperative changes in cancer cells and surrounding environment as well as the alterations in the immune system. Several trials are ongoing to develop new diagnostic and therapeutic options for minimal residual cancer after surgery.

Antioxidant Activity Open Access

Antioxidant Protection of Donor Packed Red Blood Cells using Mexidol

Sep 2018 DOI 10.14302/issn.2471-2140.jaa-18-2283
D.V. GavryuchenkovCorresponding author First Moscow State Medical University Named after I.M. Sechenov, Department of Life Safety and Emergency Disasters Medicine, Moscow, Russia.

The current research shows the possibility of long-term conservation of the erythrocytes an-tioxidant activity in the process of donor packed red blood cells while introducing mexidol to the hemoconservant glugicir composition.

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.

Advanced Cytology Open Access

The Biological Basis of Cellular Diabetes Mellitus

Sep 2018
Alnaji AbbasCorresponding author Consultant Neurosurgeon, Al-sadir medical city, Najaf, Iraq

This letter presents a clinician's perspective on the biological basis of diabetes mellitus at the cellular level. Drawing on neurosurgical practice, the author argues that persistent dysglycemia hinders recovery and may reflect long-standing intracellular processes, calling for causal, interdisciplinary management beyond symptomatic care. The piece outlines testable hypotheses and invites further laboratory validation.

Membrane Pump Operation Synchronicity (Criticality) in Epidermal Cells: The Possibility of Quantifying the Level of Synchronization

Sep 2018 DOI 10.14302/issn.2641-9181.ijnr-18-2226
V.I.PetukhovCorresponding author Vladimir State University, Vladimir, Russia

The authors analyze the results of atomic emission spectrometry of hair samples for Al, Cd, Fe, Cr, Cu, Li, Pb, V, and Zn in 952 healthy subjects and 952 liquidators of the Chernobyl nuclear power plant accident. Using correlation analysis (Pearson) of the obtained data, the authors have found pair correlations between metal concentration values. According to the authors, criticality or synchronization (as a particular case of the critical state of the system) can be inherent in all ATP-dependent membrane pumps (P-type) controlling metal-ligand homeostasis in epidermal cells. A quantitative criterion (synchronization index) is proposed to measure the level of criticality (synchronization) in the functioning of membrane ATPases.

Assessment of Biofield Energy Healing Based Vitamin D3 Effects on Bone Health Parameters Using Human Osteoblast Cell Line (MG-63)

Aug 2018 DOI 10.14302/issn.2379-7835.ijn-18-2301
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd.,Bhopal, India

Poor bone health is the primary health issue, which leads to significant health problems, stress and worsening the patients' quality of life. The potential of The Trivedi Effect®- Biofield Energy Healing on vitamin D3 as a test item (TI) and DMEM on MG-63 cells was investigated. The test items were treated with The Trivedi Effect® by Mahendra Kumar Trivedi and divided as Biofield Energy Treated (BT) and untreated (UT) test items. An increase in ALP activity, collagen levels, and bone mineralization was considered as the biomarker for bone health. MTT data showed that the test samples observed nontoxic in the tested concentrations. The level of ALP was significantly increased by 832.9% and 209.4% in the UT-DMEM+BT-TI and BT-DMEM+UT-TI groups, respectively at 10 µg/mL, while 222.9% increase in the BT-DMEM+BT-TI at 1 µg/mL compared to the untreated group. Collagen was significantly increased by 487.7% and 544.5% in the BT-DMEM+UT-TI and BT-DMEM+BT-TI groups, respectively at 100 µg/mL, while 116.2% at 1 µg/mL in UT-DMEM+BT-TI compared to the untreated group. Moreover, the percent of bone mineralization was significantly increased in the UT-DMEM+BT-TI and BT-DMEM+UT-TI groups by 344.9% and 149.7%, respectively at 50 µg/mL, while 183.6% in the BT-DMEM+BT-TI group at 100 µg/mL compared to the untreated group. Thus, the role of Biofield Energy Treated vitamin D3 and DMEM in order to control osteoblast function and its direct effects on bone mineralization can be used to improve bone disorders.

Assessment of Energy of Consciousness Healing on Cell Growth of Plant Stem Cells Callus Culture

Aug 2018 DOI 10.14302/issn.2578-8590.ipj-18-2309
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd.,Bhopal, India

The present study was aimed to evaluate the effect of Consciousness Energy Healing Treatment on plant callus of Mandukparni (Centellaasiatica), Katsarika (Barleriacristata), and Amla (Phyllanthus emblica) in Murashige & Skoog liquid medium (MS) for its growth and yield on day 7. The plant callus of all the three plants were divided into two parts, one part received Biofield Energy Treatment remotely (known as The Trivedi Effect®-Energy of Consciousness Healing Treatment) by a renowned Biofield Energy Healer, Gopal Nayak and denoted as Biofield Energy Treated group, while another part did not receive any treatment and defined as control. Plants callus were observed on day 7 after treatment and visualized under phase contrast microscope for cell growth, captured photomicrographs along with wet weight compared with day 0. Results suggested that three plants viz. Mandukparni, Katsarika, and Amla callus after 7 days showed a significant improved growth rate as compared with the respective untreated groups. The weight of the callus growth (in mg) after Biofield Energy Treatment among Mandukparni, Katsarika, and Amla callus on day 7 was 630, 782, and 920 mg, respectively. However, the percentage increase in weight of the callus in Mandukparni, Katsarika and Amla was 11.1%, 52.4%, and 68.5%, respectively than untreated. Hence, results concluded a significant growth in callus weight after Biofield Energy Treatment, which suggested the action as complementary and alternate approach in order to produce most high-value phytoconstituents from plant callus that can be used for making various drugs, food flavoring and colouring agents.

Silver Nanoparticles: Cytotoxic and Apoptotic Activity on HT-29 and A549 Cell Lines

Aug 2018 DOI 10.14302/issn.2377-2549.jndc-18-2116
Sarani MinaCorresponding author Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences.

Silver nanoparticles (Ag-NPs) are versatile materials with a broad range of applications in various fields such as cancer therapy, drug delivery. In this work, cytotoxic and apoptotic activities of silver nanoparticles was evaluation against lung (A549) and colon (HT-29) cell lines. The cytotoxic activity of nanoparticles was performed by MTT assay, while their apoptotic activity was tested through TUNEL method. The results of MTT of A549 have illustrate that fifty percent of cells destruction in concentrations more than 250 µg/ml of Ag-NPs. Apoptotic results of nanoparticles have shown more than fifty percent of apoptosis on A549 cell line. HT-29 display full apoptosis at concentrations more than 500 µg/ml. It seems that synthesized Ag-NPs by using P. farcta extract can be candidate as anti-cancer agent in treatment many cancers through creating or discovering new drug forms

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.

Clinical and Laboratory Predictors of Elevated TRV In Sickle Cell Anaemia

Jun 2018 DOI 10.14302/issn.2372-6601.jhor-18-2139
S. Afriyie-Mensah JaneCorresponding author Department of Medicine and therapeutics, School of Medicine and Dentistry, College of Health Sciences university of Ghana, Accra, Ghana.

Pulmonary hypertension (PH) has become an increasingly recognized complication in sickle cell anaemia (SCA) and is a major cause of morbidity and mortality. Though the burden of SCA in sub-Saharan Africa is high, there is paucity of data on SCA-associated PH with little or no attention given to it in routine patient care. The current study therefore sought to determine the prevalence of PH and its associated risk factors among adult patients with SCA. This was a cross-sectional study involving 76 clinically stable, hydroxyurea-naive participants. We obtained socio-demographic and clinical history. Measurement of Tricuspid Regurgitant jet Velocity (TRV) was obtained via transthoracic echocardiography and lung function was assessed using spirometry and pulse oximetry. Other investigations were complete blood counts, free plasma haemoglobin, serum urea and creatinine. Twenty-five (32.9%) of study participants had elevated TRV (≥ 2.5m/s) on Doppler echocardiography, which was suggestive of raised pulmonary artery systolic pressure. There were significant associations between elevated TRV and steady-state haemoglobin (p < 0.001), blood urea level (p = 0.030), presence of chronic leg ulcers (p = 0.043) and oxygen saturation (p < 0.001) and these may be identifiable and modifiable risk factors for selective screening with echocardiography in a resource poor setting. 

Enzymes Open Access

Hydrolysis of Cellulose by Soluble Clostridium Thermocellum and Acidothermus Cellulolyticus Cellulases

Apr 2018 DOI 10.14302/issn.2690-4829.jen-18-2025
Brumm PhillipCorresponding author C5-6 Technologies LLC, 5627 Old Oak Drive, Fitchburg, WI 53711, USA

The goal of this work was to clone, express, characterize and assemble a set of soluble thermostablecellulases capable of significantly degrading cellulose. We successfully cloned, expressed, and purified eleven Clostridium thermocellum (Cthe) cellulases and eight Acidothermuscellulolyticus(Acel) cellulases. The performance of the nineteen enzymes was evaluated on crystalline (filter paper) and amorphous (PASC) cellulose. Hydrolysis products generated from these two substrates were converted to glucose using beta-glucosidase and the glucose formed was determined enzymatically. Ten of the eleven Cthe enzymes were highly active on amorphous cellulose. The individual enzymes all produced <10% reducing sugar equivalents from filter paper. Combinations of Cthe cellulases gave higher conversions, with the combination of CelE, CelI, CelG, and CelK converting 34% of the crystalline cellulose. All eight Acel cellulases showed endo-cellulase activity and were highly active on PASC. Only Acel_0615 produced more than 10% reducing sugar equivalents from filter paper, and a combination of six Acel cellulases produced 32% conversion. Acel_0617, a GH48 exo-cellulase, and Acel_0619, a GH12 endo-cellulase, synergistically stimulated cellulose degradation by the combination of Cthe cellulases to almost 80%. Addition of both Acel enzymes to the Cthe enzyme mix did not further stimulate hydrolysis. Cthe CelG and CelI stimulated cellulose degradation by the combination of Acel cellulases to 66%.

Coolifting® CoolCell®, A New Group of Highly Effective Active Ingredients for the Reduction of Cellulite in Women

Apr 2018 DOI 10.14302/issn.2640-6403.jtrr-18-2054
Pinto HernánCorresponding author i2e3 Biomedical Research Institute, Barcelona, Spain

Cellulite is a very frequent clinical condition that, despite not being serious, constitutes one of the greatest aesthetic concerns of a large number of women. In recent years, some of the technologies that have allowed the development of devices and key tools in aesthetic medicine treatments have been consolidated. The aim of this article is to test the effectiveness of CoolCell®, a new treatment for cellulite that is administered with Coolifting® technology. We included 24 women who received 8 sessions of Coolifting® CoolCell®, one per week. Thermographic measurements were taken and satisfaction questionnaires were completed. Thermographic analysis showed a statistically significant color variation and self-assessment reports revealed that more around 75% of the subjects witnessed great or spectacular changes on their skin.

Successful Allogeneic Hematopoietic Stem Cell Transplantation from A 5/10 Mismatched Unrelated Donor in A Patient with Donor-Specific Anti-HLA Antibodies.

Apr 2018 DOI 10.14302/issn.2372-6601.jhor-18-1988
M RoviraCorresponding author Bone Marrow Transplantation Unit. Hematology Department. Hospital Clinic-IDIBAPS. Josep Carreras Leukaemia Research Institute (IJC)

Hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor, an haploidentical donor or a cord blood unit (CBU) has become a widely aviable approach if patient lacks a matched related or unrelated donor. However, if the patient has anti-HLA antibodies against antigens present in the mismatched donor or CBU (donor-specific antibodies, DSAs) this option should be disregarded due to the high risk of graft failure. Desensitization can be used to reduce levels of DSAs but this technique has limited results. We report the case of a 62-year-old woman with DSAs against two haploidentical familiar donors who failed desensitization of DSAs. Finally she underwent a HSCT from a 5/10 mismatched unrelated donor which has been successful.

Biomaterials Open Access

Nanotechnology Meets Immunotherapy: CAR-T Cells Technology and Beyond

Mar 2018
Rizzello LorisCorresponding author Department of Chemistry, University College London (UCL), 20 Gordon Street, WC1H 0AJ - London (UK)

The crusade against cancer has a new army: immunotherapy. The rational design is very simple, but brilliant at the same time. Extract the patients T-cells, reprogram them in vitro for the expression of highly specific receptors against cancer, perfuse them back to the patient. As a result, T-cells are now instructed to selectively kill circulating tumor cells, while avoiding potential side effects. This ‘Fairy Tale’ however does not lack of drawbacks and limitations. First, malignant progression can be accompanied by profound immune suppression, which counteracts the immune system-mediated tumor elimination. Second, the immune cells modification does not match high standards in terms of safety for humans. Here, nanotech can fill these gaps, and help immunotherapy to be safer and more effective.

β-Cell function in type 1 diabetes may not be as low as presumed

Feb 2018 DOI 10.14302/issn.3070-2313.jeh-17-1756
Tamer GoncaCorresponding author Division of Endocrinology and Metabolism, Department of Internal Medicine, Medeniyet University, Göztepe Training and Research Hospital, Istanbul.

Objective We aimed to evaluate β-cell function of type 1 diabetic patients (T1DP)s based on fasting and stimulated C-peptide levels. Material and methods Study included 135 T1DPs and 31 healthy subjects. Fasting C-peptide levels were measured in healthy subjects and T1DPs. The Mixed-meal tolerance test (MMTT) was performed in T1DPs. Fasting and stimulated (90 minute post MMTT) C-peptide levels were measured via electrochemiluminescence assay. Two categorizations were made according to fasting (the first categorization ) and at 90th minute MMTT (the second categorization) C-peptide levels. For the first categorization; the groups were classified as follows: patients with undetectable ≤0.1ng/mL(group1); minimal 0.1-0.8ng/mL(group2); and sustained ≥0.8ng/mL (group3) C-peptide levels. For the second categorization, groups were as follows: patients with undetectable ≤0.1 ng/mL(group1); minimal 0.1-0.8 ng/ml (group2); and sustained ≥0.8ng/mL (group3) in which C peptide levels were increased to ≥150% of fasting C-peptide levels at the 90th minute after MMTT. Results For the first category; 41.5%, 40% and 18.5% of T1DPs were in group1, group2 and group3, respectively. For the second category; 34.8%, 20.7% and 44.4% were in group1, group2 and group3, respectively. In first categorization 58.5% and in second categorization 65.1% of T1DPs had detectable C-peptide levels. 44,4%of the T1DPs had a response to MMTT with C-peptide levels ≥0.8 ng/mL which increased to ≥150% of fasting C-peptide level at the 90th minute after MMTT as it is seen in non-diabetics. Conclusion The present study suggests the presence of functioning β-cells in T1DPs and 44.4 % of T1DPs have a response to MMTT as seen in non-diabetics. (ClinicalTrials.gov number: NCT02199470.)

Antioxidant Activity Open Access

Some Aspects of Regulatory Criteria for Metal-ligand Homeostasis in Epidermal Cells

Jan 2018 DOI 10.14302/issn.2471-2140.jaa-17-1927
V.I.PetukhovCorresponding author Vladimir State University, Vladimir, Russia

The work is dedicated to the problem of the norm in the quantitative evaluation of metal content in the epidermal cells (hair) obtained by the method of spectrometry. Authors have analyzed the hair samples for Zn, Cu, and Fe content, which were obtained from 10000 healthy subjects (5000 males and 5000 females aged 20 to 45). The definition of the norm, in the authors’ opinion, is closely related to the basic positions of the theory of self-organized criticality (SC). The observed shifts in the homeostasis of essential metals are local and therefore cannot serve as a criterion of sufficient (or insufficient) metal content throughout the body.

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.

First Evidences of Epithelial-Mesenchymal Transition and Cancer Stem-Cell Phenotype Acquisition in Dermo-Epidermal Junction of BPV-Infected Neoplasms

Dec 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1869
de Cassia Stocco RitaCorresponding author Genetics Laboratory, Butantan Institute, São Paulo-SP, Brazil

Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).

Cellular Mechanics and Therapeutic Resistance of the Cancer Relapse

Dec 2017 DOI 10.14302/issn.2766-8630.jrnm-17-1770
Y. Moawad EmadCorresponding author Independent researcher graduated from department of engineering, Ain Shams University

The aims of this study are to investigate the variation in the mechanical behaviour of the primary cancer from cancer relapse, and measuring the therapeutic resistance acquired by cancer relapse. A431-cultured cells were irradiated for 7 months until 85 Gy. Then, a selected single cell was left to grow as stable A431-R cell line. 106 cells of A431 cells and 106 of A431-R cells suspended in 100 μL of medium were injected into subcutaneous tissues on the right thigh of athymic mice to generate tumor xenografts models of primary cancer (A431-P) and cancer relapse (A431-R). Radiotherapy of a low-dose of 30Gy was applied on xenoimplanted tumors after one week from inoculation. A mock process was performed on untreated groups of mice for controls. Tumor size was monitored starting from inoculation and tumor growth was measured along 42 days. Rates of mitosis and apoptosis and the histologic grade (HG) that characterize the tumor response were determined as described in earlier studies. Alterations induced on tumor HG in the treated models were 100% identical to the energy of the applied doses. The differences in response energy between cancer relapse and primary cancer irrespectively of the treatment (untreated vs. treated) or origin of the cells (A431-P vs. A431-R) in all phases of tumor responses (growth, shrinkage or regrowth) were 100% identical to the total differences in the administered regimens applied on those groups during those phases. Cancer relapse is characterized by a delay in growth before second line therapy for its relatively lower rate of mitosis compared by the primary cancer inducing a corresponding delay in the early detection. The therapeutic resistance of the cancer relapse is equivalent to the energy of the doses which have been delivered in the prior therapies, and requires increasing the administered dose by an amount equivalent to that resistance.

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.

Squamous Cell Carcinoma of the Conjunctiva (Scc) and Human Immunodefisciency Virus (Hiv): What Reality in Ivory Coast Through 23 Cases?

Sep 2017 DOI 10.14302/issn.2324-7339.jcrhap-17-1694
Coulibaly R BereteCorresponding author Ophthalmology Department of University Hospital of Treichville

Introduction: Squamous cell carcinomas of the conjunctiva (SCC) are rare neoplasia but have a high rate of increase and a high rate of mortality, especially when they occur in the context of Human Immunodeficiency Virus (HIV) infection. The objective of this study was to establish an epidemiological and clinical profile of SCC in patients living with HIV and to assess its evolutionary characteristics. Patients and Methods: this was a descriptive cross-sectional study carried out over a period of 5 years in the ophthalmology department of the University Hospital of Treichville. The data collected focused on epidemiological, clinical, pathological, therapeutic and evolutionary elements. Twenty tree eyes of 23 patients were examined during this period. Results: The average age of our patients was 45 years with extremes ranging from 31 to 60 years. A female predominance was observed with a sex ratio of 0.92. The average consultation period was 18 months with extremes ranging from 6 to 60 months. Physically, 35% of our eyes (08 eyes) presented a functional loss of the eye. All our patients had a HIV positive status with 16 cases of HIV1 infection, 4 cases of HIV 2 infection and 3 cases of HIV 1 and 2 co-infection. Lymphocyte typing was performed for 15 patients out of the 23 With CD4 cell counts ˂ 200 in 30.43% of cases, between 200 and 500 in 34.78% of cases. All our tumors had had biopsy excision with pathological examination. A postoperative adjuvant topical chemotherapy in 6 cases. The average follow-up period of our patients was 29 months. In all cases, it was invasive differentiated squamous cell carcinoma. Discussion: HIV infection is a risk factor for the occurrence of conjunctival squamous cell carcinoma, but it is also an aggravating factor especially in the case of low CD4 cell count, particularly in sub-Saharan Africa, where the fight against infection, although boosted in these recent years, is far to achieve all objectives Conclusion: HIV seroprevalence is very often associated with opportunistic infections which include carcinogenic processes such as squamous cell carcinomas of the conjunctiva

Expression of Estrogen Receptor β in Hypothalamic Stem Cells

Jul 2017 DOI 10.14302/issn.2574-4372.jesr-17-1611
He ZhenCorresponding author Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, USA 72079

Neural stem cell activity at least partially accounts for the postweaning development of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and estrogen selectively mobilizes neural stem cells in the 3rd ventricle stem cell niche (3VSCN). Here, we examined the expression of estrogen receptor β (ERβ) in the SDN-POA and the 3VSCN. A subset of cells within the SDN-POA--delineated with or without calbindin D28K (CB28)-immunoreactivity (ir)--exhibited ERβ-ir. The ependymal cells that expressed nestin within the 3VSCN also expressed ERβ. Interestingly, a few proliferating (Ki67 positive) cells within the 3VSCN and the hypothalamic parenchyma, including the SDN-POA, displayed ERβ-ir. In parallel, a subset of cells in the subventricular zone was double-labeled with nestin and ERβ or Ki67 and ERβ while the subgranular zone exhibited few such double-labeled cells. ERβ is expressed in hypothalamic stem cells that may regulate cell regenerative cycles.

Neoplasms Open Access

Tumor Growth Dynamics: Dietary Fish Oil Induced Inhibition of Human Breast Carcinoma Growth, A Phenomenon of Reduced Cellular DNA Synthesis or Increased Cell Loss?

Jul 2017 DOI 10.14302/issn.2639-1716.jn-17-1495
J Gonzalez MichaelCorresponding author University of Puerto Rico Medical Sciences Campus, Schools of Public Health and Pharmacy, San Juan PR.

Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic processes, via an effect on tumor cell proliferation or tumor cell loss, has not been clearly established. In the studies described in this communication, three methods were utilized to study tumor cell proliferation, i.e., H3-thymidine autoradiographic analysis, 5-bromo 2'-deoxyuridine (Brdu) flow cytometric analysis, and proliferative cell nuclear antigen (PCNA) flow cytometric analysis. Two methods were used to study tumor cell loss, i.e., a determination of the I125Urd tumor emission rate and a determination of a cell loss factor from the formulas of Steel and Begg. The tumor examined was the human breast carcinoma cell line MDA- MB231 maintained in athymic nude mouse. No significant difference in cell proliferation between carcinomas of mice fed a high corn oil diet (20% w/w) and a diet high in fish oil (19% menhaden oil, 1% corn oil). In contrast, a significant (p<0.05) increase in the rate of I125Urd emission rate and cell loss factor from the carcinomas in the fish oil fed mice compared to the corn oil fed mice was observed. In summary, the decreased tumor volume in the human breast carcinomas maintained in athymic nude mice fed a fish oil diet as compared to those fed a corn oil diet, appears to be due, at least in part, to an increased rate of carcinoma cell loss rather than a decreased rate of carcinoma cell proliferation.

Raising HLA-E-Restricted HIV-1-Specific Immune Responses Through T Cell Vaccination: A Hypothesis

Jun 2017 DOI 10.14302/issn.2690-4721.ijcm-17-1533
Soon Hoe BSc (Hon) HoCorresponding author Independent Researcher

This essay draws on recent evidences from SIV vaccination studies in rhesus macaques to argue for the potential importance of HIV-1-specific CD8+ T cells restricted by the non-classical major histocompatibility complex, HLA-E, in controlling HIV-1 replication. It then seeks to present a possible method of inducing such responses through the procedure of T cell vaccination using activated autoimmune CD4+ T lymphocytes ‘infected’ with inactivated replication-incompetent structurally intact HIV-1 particles. It is hoped that the argument presented here will interest many of those involved in HIV/AIDS research and others in the general scientific community.

Ophthalmic Science Open Access

Macular Ganglion Cell Layer Thickness in Patients Using Oral Isotretinoin

Jun 2017 DOI 10.14302/issn.2470-0436.jos-17-1442
Kocamis OzkanCorresponding author Ozkan Kocamis, Ahi Evran University, Medical School Ophthalmology Clinic, irsehir, Turkey

Objective: Determining the effects on macular ganglion cell layer thickness in patients using isotretinoin by utilization of optical coherence tomography. Material and Methods: Sixty eyes of 30 patients using isotretinoin and 60 eyes of 30 control group patients in the same age range were included in this study. The average age of the patients using isotretinoin was; 21.2 ± 3.62 years, whereas the average age of the patients in the control group was 22.7 ± 3.7 years. The thickness of the macular ganglion cell layer (GCL), the retinal nerve fiber layer (RNFL) and subfoveal macular thickness of all patients were measured with optical coherence tomography (OCT). Results: The macular ganglion cell layer thickness in the OCT of the patients using isotretinoin was measured as 61.6±4.6 µm, 62.4±4.4µm, for the right and left eye respectively, whereas the thickness in the control group was measured as 60.6±4.1µm, 61.2±4.9µm respectively. The retinal nerve fiber layer thickness in the OCT of the patients using isotretinoin was measured as 74.8±11.3µm, 76.2±12.3µm, for the right and left eye respectively, whereas the thickness in the control group was measured as 72.2±10.5µm, 74.1±1.9µm, respectively. Conclusions: No statistically significant difference was observed in the macular ganglion cell layer thickness, retinal nerve fiber layer thickness and macular thickness in terms of both the right and left eyes between the control group and patients using isotretinoin.

Ophthalmic Science Open Access

Transiently Raised IOP Equivalent to That Experienced During Ocular Surgery Causes Moderate Inflammation but does not Affect Retinal Function or Result in Retinal Ganglion Cell Loss in An Animal Model

May 2017 DOI 10.14302/issn.2470-0436.jos-17-1453
Zhang JieCorresponding author Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Private bag 92019, Auckland 1142, New Zealand.

Purpose: High intraocular pressure (IOP) is known to result in retinal ganglion cell (RGC) loss, both with chronically raised intraocular pressure (such as with glaucoma) and with acute raises in pressure (due to injury or acute angle closure). Because IOP is often raised during ocular surgery, the purpose of this study was to evaluate the effect of transient moderate IOP on retinal function, RGC survival and the expression of Connexin 43 (Cx43) and glial fibrillary acidic protein (GFAP), ubiquitously expressed central nervous system (CNS) proteins that are known to be elevated during the retinal inflammatory response to injury. Materials and Methods: Wistar rats were exposed to transient IOP at 40 mmHg for 5 or 30 minutes, and 60 mmHg for 5 minutes (via cannulation of the anterior chamber with a saline reservoir raised to a height corresponding to the desired IOP), mimicking potential IOP rises during surgery such as DSAEK and some laser procedures (LASIK and femtosecond laser cataract surgery). Separate groups of animals had IOP maintained at 10 mmHg for 5 or 30 minutes as cannulation controls, or 120 mmHg for 60 minutes as positive controls. Changes in the optic nerve and retina were assessed immunohistochemically for GFAP and Cx43 expression. Retinal function was assessed using electroretinography (ERG) recorded at baseline and 14 days after the IOP rise and compared with RGC counts. Results: Results showed that there was a differential GFAP labelling pattern observed in the anterior optic nerve in the 40 mmHg 30 minute and 60 mmHg 5 minute groups 4 hours after manipulation. Gap junction protein Cx43 was minimally up-regulated in the retina in the short-term. There was, however, minimal long-term effect on retinal function and no RGC loss. Conclusions: n conclusion, elevations of IOP that are short in duration such as those occurring during surgical procedures, do not cause significant changes long-term in retinal function or RGC survival. Key Messages: Cx43 and GFAP are known to be elevated during the retinal inflammatory response to injury. No previous study has explored the effect of moderate and relatively short increases in IOP on the initial inflammatory response. We observed a mild glial inflammatory response in the anterior optic nerve, but only a minimal up-regulation of Cx43. However, transient and moderate IOP rises did not induce long term disruption to RGC function or number as measured by electrophysiology and RGC counts, respectively. This is applicable to clinical practice, as it means the IOP elevations that occur during some surgical procedures are unlikely to be causing long term damage in retinal function or RGC survival.

Bone Marrow Biology Open Access

The Effect of HLA-DRB1 Allele Mismatch on the Results after Hematopoietic Stem Cell Transplantation

Mar 2017
Remberger MatsCorresponding author Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital,

This article examines how HLA‑DRB1 allele mismatching influences outcomes after hematopoietic stem cell transplantation. It reviews graft‑versus‑host disease risk, engraftment, and survival metrics in the context of donor matching strategies. The findings support careful allele‑level typing to optimize donor selection and improve post‑transplant prognosis.

Dual Effects of Neuroprotection and Neurotoxicity by General Anesthetics on Neural Stem Cells: Role of Autophagy

Feb 2017 DOI 10.14302/issn.2574-4372.jesr-16-1380
Wei HuafengCorresponding author Department of Anesthesiology and Critical Care, Perelman School of Medicine,

General anesthetics (GAs) are widely used for various essential surgical or medical procedures. Recent studies implicate the GAs has dual effects of neuroprotection and neurotoxicity on neurogenesis with unclear mechanisms. This minireview summarizes recent studies on GAs mediated effects on neurogenesis and proposed mechanisms, with focus on autophagy regulation and intracellular calcium homeostasis.

Emerging Paradigms in Regenerative Medicine: Stem cell Therapies

Feb 2017 DOI 10.14302/issn.2574-4372.jesr-16-1382
K. Sharma BhuvneshCorresponding author R&D (Translational Oncology), ScyTek Labs., Inc. Logan, UT, USA

Stem cell research is now emerging as most exciting and promising area of modern biomedical research which has enormous potential for easing suffering for many diseases such as Parkinson’s, Alzheimer’s, Diabetes,Cancer and many more. This is now recognized most promising alternate therapeutic choice for some of the diseases which currently have no other option of an effective therapy. The Stem cell therapy is now strengthened by cutting- edge technologies and rigorous standards of clinical research thus rapidly progressed from bench to the clinic.

Human Umbilical Cord-Derived Mesenchymal Stem Cells as a Source of Odontoblasts: a GMP-compliant Approach

Jan 2017 DOI 10.14302/issn.2574-4372.jesr-16-1327
Zanini CristinaCorresponding author EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre (MBC), University of Turin, Turin, Italy.

Stem cell-based regenerative therapy can be considered an innovative approach for curing dental caries. Pulp stem cells from human exfoliated deciduous teeth (SHEDs) represent a source of committed cells for generating odontoblasts in vitro; however, SHEDs are not easy to obtain and are limited in quantity. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered to be adult stem cells that can be easily obtained in large numbers. Here, SHEDs and UC-MSCs were conditioned in custom-made serum-free culture media in order to induce differentiation towards odontoblasts. SHEDs and UC-MSCs were expanded in vitro and differentiated into odontoblasts for 21 days using a medium containing transforming growth factor-β (TGF-b3), hepatocyte growth factor (HGF) and growth differentiation factor 5 (GDF5). The ability to induce odontoblast differentiation with a straightforward clinical protocol in compliance with good manufactoring practice (GMP), which avoids animal reagents, and uses unrelated stem cells of unrestricted availability, may be a first step towards a new innovative approach for dentin regeneration.

Importance of Neutrophil/Lymphocyte Ratio in Squamous-Cell Carcinoma of the Larynx

Jan 2017 DOI 10.14302/issn.2379-8572.joa-16-1399
fatih topuz MuhammetCorresponding author Marmara University, Department of Otorhinolaryngology, Kartal, İstanbul

Aim: The relation between inflammation and cancer has been known since the 19th century. However, investigations on the pathogenesis and pathophysiology of this relation have begun recently. It was demonstrated that increased neutrophil/lymphocyte ratio is a poor prognostic factor in some malignancies. The present study aimed to determine whether preoperative neutrophil/lymphocyte ratio has a prognostic value in larynx cancer. Method: Preoperative blood analyses of 139 patients, who underwent subtotal or total laryngectomy for larynx cancer between 2003 and 2013 at Marmara University School of Medicine, Department of ENT, were retrospectively evaluated. Neutrophil/lymphocyte ratio (NLR) was calculated dividing absolute neutrophil count by absolute lymphocyte count. Optimal cut-off value for NLR was determined by receiver operating characteristics (ROC) curve analysis. Statistical analyses were done using IBM SPSS statistic 22.0 (IBM SPSS, Turkey) and Med Calc 12.3.0 package programs. Results: The sensitivity of NLR in predicting advanced-stage (Stage 3 and 4) squamous-cell carcinoma of the larynx (LSSC), T4 LSSC and lymph node metastasis at different cut-off values were 66.2%, 83.9% and 73.8%, respectively and the specificity was 76.7%, 66.2% and 65.2%, respectively. Staging according to T classification revealed that NLR significantly increases with tumor stage (p<0.001). Statistically significant relation was determined between lymph node metastasis of tumor and neutrophil/lymphocyte ratio (p=0.003). Comparing overall survival (OS) and disease-free survival (DFS) between the cases with NLR <3.02 and the cases with NLR >3.02, it was demonstrated that OS and DFS are significantly lower in the cases with NLR<3.02 (p: 0.001 vs. p<0.05 for OS and p: 0.013 vs. p<0.05 for DFS) Conclusion: NLR increases with the stage of disease in LSSC. NLR is a simple, cheap, repeatable and valuable parameter that can be obtained from routine analyses, gives information about poor prognosis and survival, and is able to predict T4 LSSC, advanced-stage LSSC (stage 3-4) and lymph node metastasis.

Immune Thrombocytopenia after Allogeneic Stem Cell Transplantation: Case Report and Brief Overview of Treatment Strategies

Dec 2016 DOI 10.14302/issn.2372-6601.jhor-16-1330
Ferrarini IsaccoCorresponding author Section of Hematology, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

Immune thrombocytopenia (ITP) is a rare but well-recognized post-allogeneic hematopoietic stem cell transplant (HSCT) autoimmune complication for which a standard treatment approach is lacking. Herein we report on an adult patient affected by high-risk acute myeloid leukemia (AML) who developed a post-HSCT ITP. Due to the refractoriness to first-line therapies the patient underwent the thrombopoietin (TPO) mimetic Eltrombopag obtaining the ITP resolution. We also discuss the clinical course of ITP in post-HSCT setting and pros and cons of different therapeutic strategies, focusing on the emerging role of TPO mimetics.

Adenosquamous Cell Carcinoma of the Stomach 18F-FDG PET/CT Diagnosis and Review of Literature

Nov 2016 DOI 10.14302/issn.2574-4526.jddd-16-1311
M DarouichiCorresponding author Department of radiology

Adenosquamous carcinoma of the stomach (ASCS) is extremely rare with less than one hundred cases published in the world literature. It is defined by combined adenocarcima and squamous cells carcinoma of the stomach. ASCS is clinically aggressive and has a poor prognosis, even when discovered at an early stage. This intriguing entity is characterized by non specific symptoms or radiological signs. Integrate 18F-fluorodeoxyglucose positron emission tomography/computed tomography 18F FDG.PET/CT is useful morphologic and functional modalities for evaluating primary tumor, local extend and invasion beyond gastric wall or distant metastatic and eventually for management. Diagnosis of ASCS requires immunohistochemical confirmation. We report a 77-year-old man who was admitted to hospital because of epigastric pain, vomiting and melena since more than a month. Gastroscopy with biopsies had initially suggested gastric squamous cell carcinoma .Thoracic and abdominal computed tomography scan (CT) showed a huge mass in the gastric body, largely necrotic, infiltrating the adjacent structures without metastases. Partial gastrectomy with resection of the proximal 2/3 of the stomach, the spleen, the body and tail of pancreas and the left transverse colon was performed. Immunohistochemical analysis demonstrated ASCS with mixed adenocarcinomatous and squamous cells carcinoma with invasion of gastric lymph nodes. Unfortunately, two months after surgery, a CT of the abdomen revealed diffuse metastasis and the patient died three months later. In light of this case, we discuss the pathogenesis, staging and monitoring of this rare entity by combined 18F-FDG PET/CT with review of the literature.

Does a Controlled Diet Improve Cellulite?

Jul 2016 DOI 10.14302/issn.2379-7835.ijn-16-986
S Yarak,Corresponding author Universidade Federal de São Paulo, Dermatology Department. 

Abstract: Several researchers have suggested that a targeted diet for reducing theadipose tissue may interfere with the severity of cellulite. Others emphasize that the diet composition seems to play a more relevant role than the calorie profile for weight loss and cellulite control. Objective: The aim of this study was to evaluate the influence of a controlled diet on body composition and cellulite improvement in adult women. Methods: Thirty two healthy women, aged from 25 to 40 were included. They receivedan orientation for a controlled diet to be followed for 3 months. Assessments were performed at the baseline and the end of the study which included four parameters: 1) Photonumeric cellulite severity scale; 2) Anthropometric measuremets 3) Skin elasticity (Cutometer®) and 4) Collagen density or echogenicity and length of the dermis-hypodermis interface line (ultrasonography - DermaScan®). The data was compared with the Paired T-test, Wilcoxon and Pearson's correlation for statistical analyses. Results: Only 14 completed the study. Although the scores of photonumeric scalereduced, there was no difference in the grade of cellulite severity. There were significant reductions in body measurement. The skin elasticity showed no significant change. On the other hand, the dermal density or echogenicity showed a significant increase in the right and left sides (p = 0.05 and p = 0.005, respectively); however, no difference was observed in the lenght of dermis-hypodermis line. Conclusion: the controlled diet was effective for the reduction of weight and body composition, but despite the increase in dermal collagen density, no clinical effect on cellulite could be detected.

Biocompatible Scaffolds for Human-Induced Pluripotent Stem Cell Transplantation and Modeling Post-Stroke Recovery in Three-Dimensional Neural Cell Culture

Jul 2016 DOI 10.14302/issn.2574-4372.jesr-16-1055
B. Jensen MatthewCorresponding author University of Wisconsin Department of Neurology

Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.

Cytoplasmic Retention of CDC6 Induces Premature Senescence in Immortalized Cells and Suppresses Tumor Formation in Mice

Jun 2016 DOI 10.14302/issn.2372-6601.jhor-16-1125
Kato Jun-yaCorresponding author Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan

Senescence is a powerful mechanism that prevents the development of tumors in vivo; however, once tumors are formed, most are refractory to senescence in response to oncogenic stress. Therefore, a novel pathway leading to senescence is required. We herein demonstrated that the cell cycle regulator CDC6 translocated from the nucleus to the cytoplasm during senescence in a leptomycin B-resistant manner. In order to evaluate the translocation of CDC6, we utilized an estrogen receptor (ER) tag to retain CDC6 in the cytoplasm. ER-tagged CDC6 was exclusively cytoplasmic, inhibited cell proliferation, and induced senescence-associated (SA) b-galactosidase activity. Furthermore, ER-CDC6 inhibited the transformation of mouse fibroblasts by the active ras oncogene in vitro, and suppressed tumor formation in NOD-SCID mice. Thus, CDC6 may play a critical role in the regulation of senescence in the cytoplasm in order to counteract tumorigenesis.

Evaluation of Crest Guideline Validity for Diagnosis of Non-Facial Cellulites

Jun 2016 DOI 10.14302/issn.2471-2175.jdrt-15-836
Abiri SamanehCorresponding author Department of Emergency, Iran University of Medical University, Tehran, Iran.

Cellulitis is an acute, spreading pyogenic inflammation of the dermis and subcutaneous tissue, usually complicating a wound, ulcer, or dermatosis. Inappropriate diagnosis of cellulitis is a problem and would need prospective rather than retrospective studies to quantify the extent. There is one national guideline for the management of patients with cellulitis. The aim of this study is to determine the validity of Crest guideline in the patients with non-facial cellulitis. This prospective cohort study was conducted on all Adult patients with cellulites who were admitted at Resole-Akram and Sina emergency department between November 2013 and January 2014. Based on admission duration, the patients were randomly divided into two groups including primary and secondary outcome, <24-hours or >24-hours admission, respectively. Out of 89 admitted patients, 55% were hospitalized over 24 hours and 20% of them had significant systemic symptoms. The most patients (n= 42) had either systemically ill or systemically well or class II followed by classes I (n=28), III (n=18), and IV (n=1). There was significant relevancy between age, fever, PR, infected organ, leukocytosis, diabetes mellitus, IUDA, human bite, and primary outcome. In conclusion, factors associated with admission were age, presence of multiple comorbid conditions, diabetes mellitus, human bite, IUDA, infected organ, leukocytosis and fever. These results showed that the decision in the emergency department was mostly the same as Crest guideline and the prospection of admission and discharge of these patients was almost according to the educations of Crest guideline.

Ophthalmic Science Open Access

Ciliary Neurotrophic Factor Activated Signaling Pathways in Retinal Müller Cells

Mar 2016 DOI 10.14302/issn.2470-0436.jos-15-739
P. Sarthy VijayCorresponding author Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 606111.

Ciliary neurotrophic factor (CNTF) is a well-tested, neuroprotective agent that has been shown to retard photoreceptor degeneration in several animal models of retinitis pigmentosa. The molecular mechanisms underlying CNTF-mediated neuroprotection are currently not understood. CNTF could act directly on photoreceptors or it could act indirectly by stimulating Müller glial cells to produce photoreceptor neuroprotective agents. To better characterize CNTF action on Müller cells, we have studied signaling pathways activated by CNTF using an established retinal Müller cell line, rMC-1. RNA was isolated from CNTF-treated cultures, and suppressor of signal transducer and activator of transcription (SOCS3) and Glial fibrillary acidic protein (GFAP) transcript levels were assessed by quantitative real-time PCR. Immunoblotting was used to examine activation ofmitogen activated protein kinase (ERK1/2/MAPK) and phosphoinositide 3-kinase (PI3-K)/Aktpathways in response to CNTF. Additionally, the level of5' AMP-activated protein kinase (AMPK), an enzyme that plays a key role in cellular energy homeostasis levels, was determined by immunoblotting. CNTF treatment resulted strong upregulation of SOCS3 and GFAP transcripts that were blocked by expression of a dominant-negative STAT3 mutant. CNTF treatment also resulted in transient activation of ERK1/2/MAPK but not PI3K/Akt signaling pathway. There was no change in activation of AMPK. We conclude that CNTF treatment leads to stimulation of JAK-STAT and MAPK signaling pathways but not the PI3K/AKT pathway, associated with cell death, in Müller cells.

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