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Apr 2024 DOI 10.14302/issn.2576-9383.jhhr-24-4960
Hanai ToshihikoCorresponding author
The binding strength of Covid-19 variants, Omicron BQ.1, XBB.1.5, XBB 1.16, FE.1, EG.5, BA.2.86, HV.1, and JN.1, with the ACE-2, was calculated insilicoand evaluated with previous variants; the binding strength of new variants is XBB.1.5 << BA.2.86 < Delta < JN.1 < HV.1 < BA.1 << BA.2. The binding strength of Omicron JN.1 was similar to that of Delta, and that of others was less than that of BA.2.86. The binding inhibition of natural polyphenols was analyzed using a popular Omicron JN.1. The natural polyphenols were (-) Catechin, (+) Catechin, (+) epicatechin, apigenin, apigetrin, daidzein, quercetin, genistein, and oleuropein. The ionization of phenolic hydroxy groups was defined based on the atomic partial charge of oxygen. Polyphenols’ ionized hydroxy groups inhibited the binding of JN.1 S-RPB with ACE-2.
Jun 2023 DOI 10.14302/issn.2377-2549.jndc-23-4431
Ifeanyi John ObibuenyiCorresponding author
Background of this paper investigates dogonyaro-leaf-extract as inhibitor for aluminum corrosion in 0.3-M hydrochloric acid, and its acceptability as original. In the methods, the extract was analyzed for phytochemicals and corrosion test performed on aluminum sheet before immersion in acid incorporated extract. Electrochemical Impedance Spectroscopy (EIS), tests were performed over frequency of 100 KHz–10 mHz and 10 mV peak to peak perturbation amplitude to obtain the corrosion potential. Tests were run at 30oC ± room temperature in aerated quiescent solutions. In weight loss method, coupons were suspended in aerated solutions before immersion in 20% mixture of sodium hydroxide and zinc dust to stop further corrosion. Morphology of the mirrorlike finished arid surface aluminum was measured with scanning electron microscope SEM. In the results, various phytochemicals were observed; significant effect of incorporating inhibitor on EIS data recorded and optimum extract efficiency was 99.46%, at 10 g/l, 60oC, within 6 hours. This result was validated and 99.3% efficiency obtained. Introduction of extract into acid corrodents caused increase of charge transfer resistance and reduced double layer capacitance. A warm arid clean coupon evolved after SEM test. In conclusion, there was increase in efficiency of inhibition as inhibitor concentration and temperature increased. Similarly, close responses towards the factors for Inhibition occur. Measured polarization showed that extract inhibited both cathodic and anodic reaction processes and thus, is classified as mixed type inhibitor. The investigations thus proved the extract as excellent corrosion inhibitor for aluminum in 0.3-M hydrochloric-acid.
Sep 2022 DOI 10.14302/issn.2641-4538.jphi-22-4238
Bavbek SevimCorresponding author
Department of Chest Disease, Division of Allergy and Clinical Immunology, Ankara University, School of Medicine, Ankara, Turkey
The safety of cyclooxygenase (COX)-2 inhibitors has been tested in patients who had cross-reactive hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs). However, these studies have been mainly done before the current classification of NSAID hypersensitivity and cross-reaction between COX-2 inhibitors has been rarely reported.We aimed to assess tolerability of COX-2 inhibitors and to evaluate the cross-reactivity between them in cross-reactive phenotype of NSAID hypersensitivity. The diagnosis was based on clinical features, reliable history of HSRs to at least two chemically different NSAIDs, and/or positive provocation tests with implicated NSAIDs in 151 patients. Single-blind, oral challenges with 1/4 and 3/4 divided doses of placebo, nimesulide, meloxicam, and celecoxib, as COX-2 inhibitors, were performed. The most common cross-reactive phenotype was NSAID-induced urticaria/angioedema (56.3%). Positive reactions to meloxicam, nimesulide, and celecoxib challenges were observed in 23/140 (16.4%), 7/33 (21.2%), and none of six patients, respectively. Overall, 24 patients were tested with two, one was tested with three COX-2 inhibitors. Six (31.6%) of 19 patients with meloxicam intolerance reacted to nimesulide provocation. Nimesulide, meloxicam, and celecoxib appeared safe alternatives in cross-reactive phenotypes of NSAID hypersensitivity. Although celecoxib has the most favorable tolerability, cross-reactivity among COX-2 inhibitors seems to be possible.
Jun 2021
Akonu Adom Mensah Forson KwesiCorresponding author
University of Cape Coast, Ghana
The purpose of this study was to investigate the effects of extracts of Tridax procumbens leaves a traditional medicinal plant, on α-amylase activities in vitro. The air-dried aerial parts of Tridax procumbens leaves were extracted with Petroleum ether and Ethanol. The results of both enzyme inhibition activities were found in a dose-dependent manner. The strongest activity of α-amylase inhibition was found in Petroleum ether extract (IC50 = 10.436 mg/mL) followed by ethanol extract (IC50 = 12.65 mg/mL) compared with acarbose having an IC50 value of 0.044 mg/mL. All extracts from this plant possess potent α-amylase activity inhibition which may offer a better therapeutic strategy to minimize postprandial hyperglycemia and its complications.
Nov 2019 DOI 10.14302/issn.2324-7339.jcrhap-19-3070
Sharma BechanCorresponding author
Department of Biochemistry, Faculty of Science, University of Allahabad, Allahabad-211002, UP, India.
The telomeres existing at the end of the eukaryotic chromosome, play an important role in localization, pairing of homologous chromosomes during cell division and synapsis formation, while telomerase is involved in maintenance of the telomere length. The application of antiHIV-1 molecules particularly NRTIs have been shown to interfere with telomerase function thereby inducing aging processes. Since the application of these molecules has already indicated production of oxidative stress and toxicity in AIDS patients, their adverse impact on telomerase function may further worsen the situation. In addition, the negative influence of antiHIV-1 regimens on certain host factors involved in telomerase function may enhance aging. HAART changes the landscape of the disease by progressively decreasing the progression of HIV-1, but exerts prolonged adverse effects on the telomerase function. Though there is no exact information available on this issue, intensive efforts are needed to explore regulation of telomerase expression in HIV infected individuals and particularly those receiving antiretrovirals.
Aug 2017 DOI 10.14302/issn.2470-0436.jos-17-1721
C. Rodger DamienCorresponding author
USC Roski Eye Institute, Los Angeles, California
A 57-year-old Hispanic female presented with 3 days of blurry vision in the left eye. Eight years prior, she had a branch retinal artery occlusion in the right eye and a hematologic work-up revealed a 4G/4G polymorphism in plasminogen activator inhibitor-1. With the current episode, she was found to have bilateral branch retinal artery occlusions and mild vitritis in the left eye, simulating a toxoplasma infection. An infectious and inflammatory work up, however, was negative and the vitritis resolved after a short course of steroids. Plasminogen activator inhibitor-1 mutations may be associated with an increased risk of retinal vascular occlusions.
Jan 2013 DOI 10.14302/issn.2328-0182.japst-12-99
C Korte WolfgangCorresponding author
Center for Laboratory Medicine, St. Gallen;
To date, platelet aggregation studies have not been formally evaluated in persons receiving Etodolac, a preferential cyclooxygenase-2 (COX-2) inhibitor. Our purpose was to investigate the influence of Etodolac in therapeutic (analgesic) doses (300 mg every 12h) on platelet aggregation as compared to placebo in healthy volunteers. Platelet aggregation, the primary efficacy variable in this trial, was performed according to the Born method with platelet rich plasma; it was evaluated as maximal platelet aggregation induced by 3 substances (adenosine diphosphate (ADP), epinephrine, collagen); each of these substances was used at 3 different concentrations. No significant difference in platelet aggregation as assessed by Born aggregometry was seen in volunteers treated with etodolac or placebo. Etodolac - applied in regular analgesic doses to volunteers - does not show an inhibitory effect on platelet aggregation and therefore seems an attractive analgesic substance for the perioperative setting.
Mar 2026 DOI 10.14302/issn.2994-6743.ijstd-26-6060
Francesco Amadeo PierCorresponding author
Objective To describe the clinical features and real-world treatment of people living with human immunodeficiency virus (PLHIV) using fixed-dose or free combinations of 2-drug regimens (2DR) of antiretroviral therapy (ART). Design Italian retrospective cohort study. Methods Data were extracted from PLHIV who initiated or switched to 2DR: Group 1 (fixed dose), Group 2 (free combination). Results Group 1 was younger and more predominantly male, and had shorter time from AIDS-defining diagnosis to 2DR-ART and from diagnosis to baseline, a lower prevalence of resistance, and fewer comorbidities than Group 2. Median baseline viral load was <50 copies/mL in both groups, but Group 1 had a higher mean due to outliers. The most common ART classes before switching to 2DR were Integrase Strand Transfer Inhibitor (INSTI)-based (48.97%), Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based (22.73%), and Protease Inhibitor (PI)-based (16.53%). Distribution varied: Group 1: INSTI-based (53.13%), NNRTI-based (24.31%), and PI-based (15.04%); Group 2: INSTI-based (29.41%), PI-based (23.53%), and NNRTI-based (15.29%). After switching, Group 1 was on dolutegravir/lamivudine (79,33%) and dolutegravir/rilpivirine (20,67%); Group 2 mostly on INSTI-PI (52.81%), followed by NNRTI combinations, mainly with doravirine (19.10%). Duration of ART after switching was shorter in Group 1. Conclusion Italian PLHIV on 2DR fixed-dose combinations were younger, virologically suppressed individuals at baseline, with a shorter lead time from diagnosis, lower prevalence of resistance and lower comorbidity rate compared to those on free combinations. These findings underscore an unmet need for 2DR fixed-dose combinations, as the free combinations were predominantly utilized for more challenging populations.
Dec 2025 DOI 10.14302/issn.2324-7339.jcrhap-25-5515
Rao AnaghaCorresponding author
Background Peripheral neuropathy (PN) is a common and debilitating complication in people living with HIV (PLHIV). While HIV itself contributes to neuropathy, certain antiretroviral therapy (ART) drugs, particularly nucleoside reverse transcriptase inhibitors (NRTIs) such as stavudine (d4T) and zidovudine (AZT), are known for their neurotoxic effects. Objectives To evaluate the impact of ART on HIV-associated peripheral neuropathy (HIV-PN) and to determine whether certain ART regimens increase the risk or severity of neuropathy. Materials and Methods A cross-sectional study was conducted among 158 HIV-positive patients. Neuropathy was diagnosed using clinical criteria, Total Neuropathy Score (TNS), and nerve conduction studies (NCS). Patients were grouped based on their ART regimen, and statistical analysis was performed to assess the association between ART type and peripheral neuropathy severity. Results It was noted that patients on older NRTIs (stavudine, zidovudine) had significantly higher rates of peripheral neuropathy (p=0.002) and tenofovir-based regimens were associated with lower peripheral neuropathy prevalence (p=0.01). There was a significant correlation between the duration of ART exposure and peripheral neuropathy severity (p<0.001), suggesting a cumulative neurotoxic effect. Conclusion Older ART regimens, particularly stavudine and zidovudine, significantly contribute to HIV-PN. The study supports the WHO recommendation to phase out neurotoxic ART and highlights the importance of early ART regimen optimisation to prevent long-term neurological complications.
Mar 2025 DOI 10.14302/issn.2641-5518.jcci-24-5362
L. Rivers KeithCorresponding author
Bacterial resistance to antibiotics is becoming a major public health challenge in the Bahamas. Indiscriminate use of antibiotics by medical practitioners is a major contributor to this problem. We describe a 53-year-old woman who presented with symptoms of a urinary tract infection. Empiric treatment with first- and second-line antibiotics, namely trimethoprim-sulfamethoxazole and ciprofloxacin, respectively, were ineffective in clearing the infection. After culture and sensitivity testing via minimum inhibitory concentration analysis, nitrofurantoin proved to be the only effective oral antibiotic.
May 2024 DOI 10.14302/issn.2379-7835.ijn-24-5098
Cornegliani LuisaCorresponding author
This prospective randomized double-blinded multicentric study aimed to assess the efficacy of a new nutraceutical in controlling itch and skin lesions caused by flea allergy dermatitis (FAD) and compare it with another oral product of proven efficacy. Forty-three dogs, of different age, breed and sex, with FAD were included and divided into two groups: 24 received product A and 19 product B. Both groups received the same antiparasitic treatment. A modified canine atopic lesion index (mCADLI) and pruritus visual analogic scale (pVAS) were recorded at days 0, 30 and 60. pVAS was evaluated both by the examining veterinarian (vpVAS) and the owner (opVAS). Results obtained were compared between the two groups at each time point. In both groups of dogs, a significant decrease of mCADLI, vpVAS and opVAS at day 30 and 60, compared to day 0, was observed. At baseline, the mCADLI scores of Group B were significantly higher than Group A (95% CI: -4.0 to 0.0, p < 0.05), with no differences at D30 and D60 (not significant, p > 0.05). In Group B, significantly lower values of vpVAS were observed at D30 compared to Group A (95% CI: -2.5 to 0.0, p < 0.05), but not at D60 (not significant, p > 0.05). The median values of pVAS in Group B were lower compared to Group A at both D30 (95% CI: -2.5 to 0.4, p < 0.01) and D60 (95% CI: -3.0 to 0.3, p < 0.05). Both nutraceuticals can be useful to control discomfort, skin lesions and pruritus due to flea allergy dermatitis and can be a valuable replacement for antipruritic drugs antihistamines, steroids or Il-31 inhibitors.
Apr 2024 DOI 10.14302/issn.2329-9487.jhc-24-5040
Dangwe Temoua NaibéCorresponding author
Objective Hypertensive crisis is an increasingly frequent medical condition in our context. Its management in medical emergencies is a real challenge for physicians. Few data on hypertensive crisis are available in Chad. The aim of this study was to investigate the epidemiological, clinical and prognostic characteristics of hypertensive crisis in the medical emergency department of Reference National Teaching Hospital in N'Djamena. Patient and methods This was a prospective cohort study running from 1er March 2020 to October 31 2020. Patients presenting with a sudden and severe rise in blood pressure (systolic ≥ 180 mmHg and/or diastolic ≥ 110 mmHg) with or without acute target-organs damage, had been consecutively included and followed up over a period of one (01) month. Epidemic and clinical characteristics on admission, and morbidity and mortality parameters during the course of the disease were collected. The Kaplan-Meier method and the Cox model were used to analyze survival and factors associated with death, with a significance level of p<0.05. Results Of the 3978 hypertensive patients admitted to medical emergencies, 252 had a hypertensive crisis, i.e. a prevalence of 6.3%. Two hundred and seventeen (217) patients were included in the study, divided into 149 cases (69%) of hypertensive emergency and 67 cases (31%) of hypertensive hypertensive urgencies. The mean age of the patients was 55.2 ± 14 years (20 and 80 years) and 67% were male. Hypertension was known in 138 patients (64%). At least one complication was present on admission in 69% of patients. Complications were classified as cardiac (50.7%), neurological (38.2%), kidney impairment (46.5%) and ocular (46.1%). The average number of antihypertensive drugs used was 2 ± 0.83 14. Calcium antagonists (86.5%), diuretics (35.5%), converting enzyme inhibitors or angiotensin II receptor antagonists (33.3%) and betablockers (18%) were the pharmacological classes prescribed. Good compliance during follow-up was observed in 124 patients. One-month survival was 84% for all patients, with a 16% mortality rate. Factors associated with death were the duration of hypertension, and the occurrence of cardiovascular, renal dysfunction and ocular disease (p < 0.05). Conclusion Hypertensive crisis is a frequent pathology in sub-Saharan Africa, with high morbidity and mortality. Prevention requires early detection and effective management of hypertension.
Apr 2024 DOI 10.14302/issn.2998-4211.jalr-24-4926
Bahadur Khan FaizaCorresponding author
This article has been retracted on 20 March 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2998-4211.jalr-25-5855) The research is focused on neuroinflammation a normal physiological process which is known to be associated with neurodegenerative diseases could be the potential targeted therapy via the microglia cells, it starts with defining Alzheimer’s; a neurodegenerative disease which causes deposition of Aβ (amyloid beta) protein in the cerebral cortex as well as NFT (neurofibrillary tangles) in the hippocampus and basal ganglia. The paper then describes process of neuroinflammation, microglia’s role, apolipoprotein E4 gene in relation to Alzheimer’s, which leads to different stem cell research and how pruning microglia as well as targeting microglia receptors in the brain is being used in current research trials, we included multiple meta-analysis showing microglia receptors being targeted currently by emerging drugs like propofol, antibodies CSF1R inhibitor etc, which are currently under trial phase, the research ends with concluding potential diagnostic markers like sirt1 considered to be an anti-aging protein which can be used as therapeutic interventions and Lps effect on Sirt 1. A Microglia initiated target therapy in Neuroinflammation for Alzheimer’s Patients.
Jan 2024 DOI 10.14302/issn.2574-4496.jtc-23-4835
Hussein Saleh Hussein AbbasCorresponding author
The prevalence of thyroid cancer is rapidly increasing worldwide, majorly due to overdiagnosis and overtreatment methods of differentiated thyroid cancer. The emergent and potent preclinical models, high-throughput molecular techniques, and genetic expression microarrays have delivered deeper insights into understanding the molecular features in oncogenesis. Thus, molecular markers have become a promising tool in managing thyroid cancer for differentiating benign and malignant tumors, prognosis, recurrence, and determination of novel therapeutic targets. In differentiated thyroid cancer, molecular markers are majorly utilized for guiding the development of indeterminate thyroid nodules on fine needle aspiration (FNA) histologies. Dissimilar to this, in advanced thyroid cancer, molecular markers permit targeted treatment of a modified signaling cascade. Determining causal mutation of targeted kinase receptors in advanced thyroid cancer can depict a promising treatment strategy with mutation-targeted tyrosine kinase inhibitors to reduce progression and eradicate mutation effects when conventional methods fail to manage. This review will focus on the molecular landscape and discuss the impact of molecular markers on the prognosis, treatment, and surveillance of differentiated and anaplastic thyroid cancer.
Dec 2023 DOI 10.14302/issn.2324-7339.jcrhap-23-4634
Makura AlfredCorresponding author
Introduction Human Immunodeficiency Virus (HIV) remains a persistent global public health challenge. In 2020, approximately 37.9 million individuals were living with HIV globally, including 1.7 million children <15 years old, with a global HIV prevalence of 0.8% among adults. A larger portion of people living with HIV are found in low-and middle-income countries, and Sub-Saharan Africa (SSA) is home to about 68% of people living with HIV in the world. Strikingly, with increased uptakes in PMTCT, challenges in ART programs, and high viremia among children and adolescents in SSA, the success rate of ART might be quickly compromised, with possible HIVDR emergence, particularly after years of paediatric ART exposure. Therefore, monitoring ART response in children and adolescents in terms of HIVDR patterns and other socio-economic determinants of disease progression might help achieve better treatment outcomes at individual levels. At a programmatic level, this can guide further optimization of treatment options for SSA especially Zimbabwean rural where there is paucity of information on HIVDR prevalence in children and adolescents. Methods We enrolled 89 children and adolescents experiencing virologic failure from Chidamoyo Christian Hospital in Hurungwe. We managed to amplify all the 89 using nested PCR and 32.5% (29) had resistance to at least one ART drug and analysis was done using the 29 samples. Results Among the 89 participants with virologic failure,29 were resistant to at least one of their ART drugs. 39.2% of males and 23.07% of females had HIV-1 with resistance to at least one medication. Among 29 participants with HIVDR mutations, the prevalence of at least one HIVDR mutation to protease inhibitors (PIs), Nucleotide Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleotide Reverse Transcriptase Inhibitors (NNRTI) were 6.47% ,46.76% and 46.76% respectively. Of the 29 participants who had HIVDR 19 (65.5%) had resistance to a drug they were currently taking and they needed to be switched to a better effective ART regimen Conclusion Use of HIVDR testing in guiding and monitoring development of HIVDR at the start of ART or at 1st failure can be very important in treatment options and patient management.
Sep 2023 DOI 10.14302/issn.2574-4496.jtc-23-4722
J. Conway PatrickCorresponding author
Background Patients with distant metastatic Medullary Thyroid Carcinoma (MTC) have an estimated 40% ten-year survival rate. Gain of function mutations in the REarranged during Transfection or RET gene in MTC can result in an aggressive phenotype resistant to traditional therapy. In this case report, we describe the treatment of an MTC patient with a unique RET kinase deletion mutation. Case presentation Since diagnosis, 21 years ago, this patient has had chronically elevated calcitonin levels (>40,000 pg/mL) that was unable to be controlled by conventual therapy and clinical trials. As result of uncontrolled MTC, metastatic disease was found in the spine, liver, and lungs. Circulating tumor DNA (ctDNA) analysis identified a RET 898-901Del mutation, reported as a variant of unknown significance. The treating physician identified that the deletion was in the activation loop of RET kinase and considered that the mutation was constitutively activating RET kinase. The patient was prescribed Pralsetinib, a small molecule inhibitor targeting the ATP binding site of RET. Pralsetinib treatment achieved a durable response and was able to significantly decrease serum calcitonin levels (<200 pg/mL) and tumor size. Conclusion This RET deletion mutation is a pathogenic mutation with comparable enzymatic activity to the more common RET M918T mutation. The case report highlights the versatility of structural biologic approaches to guide therapeutic decisions.
Mar 2023 DOI 10.14302/issn.2641-5518.jcci-23-4506
Partanen AnuCorresponding author
Limited data exist on the mechanisms promoting clonal expression of BCR-ABL1 cells in various myeloproliferative disorders. We present a patient whose Janus Kinase (JAK) 2 V617F-negative idiopathic myelofibrosis (IMF) transformed to Philadelphia-positive chronic myeloid leukemia (CML). A 55-year-old man had anemia and splenomegaly. Trephine biopsy showed excess fibrosis without a JAK2 V617F mutation. Diagnosis of high-risk IMF with t(3;12) and del(16q) was made. Five years later a repeated trephine biopsy showed extensive fibrosis and t(9;22) with der(22)t(9;22). BCR-ABL1 fusion gene with typical p210 fusion transcript was found resulting in the diagnosis of CML. A modest treatment response was achieved with tyrosine kinase inhibitor (TKI) therapies, but the disease eventually progressed to a myeloid blast phase. With AML-based chemotherapy plus azacytidine and a second generation TKI the patient survived for years but succumbed 11 years after the initial diagnosis. Clonal evolution may cause atypical disease characteristics or a poor response to targeted therapy in myeloproliferative disorders.
Mar 2022
Bereda GudisaCorresponding author
Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia
Dolutegravir suppresses this integration enzyme, so human immune virus can’t create every greater copies of itself, thus ‘’integrase inhibitor.’’ Dolutegravir is hastily absorbed pursuing oral administration. The median maximum plasma concentration is reached 1.5–2.5 hours after oral uptake with a mean half-life of 12–15 hours, rendering feasible for once-daily dosing without the need for pharmacological boosting. The terminal half-life is about 14 hours. The apparent oral clearance is about 1 liter/hour. Fifty three percent of the total oral dose of dolutegravir is excreted unchanged in the feces, thirty two percent through urine as glucuronide (eighteen percent) or alkylated product (three point five percent), and other organic conjugated products sequencing from phase II liver metabolisms. Dolutegravir’s categorized as pregnancy category B (no confirmation of pitfall in humans) means either animal-reproduction inquests have not substantiated a fetal peril but there are no restrained inquests in pregnant women or animal-reproduction inquests have reveal an adverse effect (distinctive than a de-escalate in fertility) that was not inveterate in restrained inquests in women in the first trimester (and there is no confirmation of a pitfall in later trimesters) or there is survey in animal that revealed the medication is safe in pregnant animal, but there is no fetal pitfall confirmation in pregnant women.Antiviral Pregnancy Registry (APR) revealed that as of January 2017, pregnancy outcomes and birth defects were analyzed from 142 pregnancies with reported exposure to DTG during pregnancy. There were 128 live births reported (3 terminations, 11 miscarriages, no stillbirths). Only 4 (3.0%) reported birth defects, which is similar to the expected rate of birth defects in the general population. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPIC) displayed that as of July 2017, 101 pregnancies with exposure to DTG had been identified with 84 birth outcomes. Rates of preterm delivery and “small for gestational age” were identical to outcomes reported from women on alternative regimens (standard of care in the United Kingdom of Great Britain and Northern Ireland).
Aug 2020 DOI 10.14302/issn.2694-1201.jsn-20-3523
Nasim Habibzadeh SeyedehCorresponding author
PhD student in Sport Science, School of Health and Life Sine, Department of Sport Science, Teesside University, United Kingdom
The brain requires certain fuels to function in high level. Literally, nutritional components can modulate the brain productivity. One of the right nutrition to enhance the brain power is dietary component of caffeine. Caffeine as a component of coffee, tea and chocolate is very popular. Although, depending on the dietary demands or conventional habits some people do not consume caffeine-containing substances (i.e. foods or beverage). Nonetheless, caffeine constituents maximize the brain potential via promoting the central nervous system (CNS) through blocking an inhibitory neurotransmitter (adenosine) and releasing some other specific neurotransmitters (noradrenaline, dopamine and serotonin) in brain. The chemistry of caffeine in a standard dose in fact can affect the brain intelligence.
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
Mar 2020 DOI 10.14302/issn.2691-8862.jvat-20-3275
Heidari AlirezaCorresponding author
Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA.
Coronavirus nanoparticles show a strong peak of Plasmon absorption in ultraviolet–visible zone. A strong interaction exists between the surface of Coronavirus nanoparticles and Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406). Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) cause to aggregation of Coronavirus nanoparticles linked to DNA/RNA and hence, lead to widening of peak Plasmon of Coronavirus nanoparticles surface at 550 (nm) and emerging a new peak at higher wavelength. In the current project, this optical characteristic of Coronavirus nanoparticles is used to time investigate of interaction between different Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) and Coronavirus nanoparticles. The results were shown that Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) with shorter chain length interact faster with Coronavirus nanoparticles. Therefore, a simple and fast method for identification of Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) with various chain length using red shift in surficial Plasmon absorption is presented.
Feb 2020 DOI 10.14302/issn.2577-2279.ijha-20-3180
Umeaku UgochukwuCorresponding author
Department of Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
Background Colon cancer is one of the leading causes of cancer death world-wide. There is a steady increase in incidence over the past four decades in developing countries. This has been partly attributed to increasingly low intake of vegetables among other causes. Aims Therefore this study aims to evaluate the protective effect of aqueous extract of Ocimumgratissimum (OG) leaves (a staple vegetable) on experimental model of colon carcinogenesis induced with 1, 2 Dimethylhydrazine (DMH). This is compared with celecoxib (a cyclooxygenase-2 inhibitor) which is used in the chemoprevention of colon cancer. Methods Sixty adult male Wistar rats were randomly divided into six groups: A to F, n=10. Group A was the normal control, Group B was given only DMH weekly for 16 weeks,Groups C, D and E were given graded doses of OG for two weeks prior to cancer induction by DMH. After which both OG and DMH were given for 16weeks. Group F received celecoxib daily for two weeks prior to cancer induction. Colonic wall was analysed grossly, histologically and biochemically. The induced lesions were staged investigated and staged using Duke’s Staging method. Results The result showed tumour incidence in groups B and C while no evidence of primary colonic tumour was observed in groups A, D, E and F. There was a dose dependent increase in the goblet cell count in the groups treated with OG with group E being statistically higher than group F. There was a significant reduction in collagen staining intensity (F = 129.74, p < 0.0001) for the colonic wall in group B when compared to other groups. There was a decreased nucleo-cytoplasmic ratio in groups C, D, E and F when compared to group B. There was a significant increase in the concentration of nitric oxide and prostaglandin E2in group B when compared to other groups D, E and F. Conclusion In conclusion, this research showed a protective effect of Ocimumgratissimum leaves on 1, 2-dimethylhydrazine-induced colon cancer which further corroborated its ethno-medicinal use.
Aug 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2953
Syed Amber Ilyas NidaCorresponding author
National Center for Proteomics, University of Karachi, Karachi 75270, Pakistan
Breast cancer has high incidence in women from both developed and developing countries. Approximately 2 million women are diagnosed with breast cancer in 2018. In Asia, unfortunately Pakistan leads the highest number of breast cancer patients. Various treatment strategies are present but they are not well developed. There is a great need to develop effective methods for early detection and treatment of the disease. For cancer treatment chemotherapeutic interventions have always been a method of choice. One of the mechanisms involved in cancerous cell proliferation is Mevalonate (MVA) pathway. It is hypothesized that arresting MVA pathway leads to cell death hence cancer cell growth is suppressed. Various inhibitors of MVA pathway have been studied that can suppress cell proliferation. Nitrogen containing bisphosphonates are MVA pathway inhibitor and clinically used for treatment of bone diseases. Their anticancer efficacy is also reported. Current study focuses on alendronate, a nitrogen containing bisphosphonate to examine their anticancer effect on breast cancer cell line. Results of this study may help in addition of new anticancer drug for breast cancer.
Jun 2019 DOI 10.14302/issn.2379-7835.ijn-19-2845
J. Johnson JeremyCorresponding author
University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice
The mangosteen fruit is a popular Southeast Asian fruit consumed for centuries. There have been a variety of xanthones isolated from the fruit, bark, roots and leaves with each having unique chemical and physical properties. Previously, the most abundant xanthone α-mangostin has been shown to inhibit CDK4. Herein we describe the role of selected xanthones from the mangosteen inhibiting CDK4. The evidence we provide here is that key functional groups are required to inhibit the CDK4 protein to prevent the phosphorylation of downstream targets critical to inhibiting uncontrolled cell cycle progression. To define the properties of xanthones for inhibiting CDK4 we utilized a cell free biochemical assay to identify inhibitors of CDK4. The following xanthones were used for the analysis: α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C and garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin These results further substantiate the unique pharmacological properties of individual xanthones and how a mixture of xanthones may be responsible for a multi-targeted effect in cell based pharmacology systems.
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.
Apr 2019 DOI 10.14302/issn.2578-8590.ipj-19-2772
Crespi FrancescoCorresponding author
Biology, CSK, Verona, Italy
Nociceptin/orphanin-FQ (NOCI) together with its receptor NOP are widely expressed in cortical and subcortical motor areas and it is known that NOCI acts as an anxiolytic attenuating the behavioral inhibition of animals acutely exposed to stressful/anxiogenic conditions. Influence of NOCI upon the dopaminergic system has been observed in the ventral tegmental area and in the nucleus accumbens as well as an inhibitory action of NOCI is described upon serotoninergic mechanisms at cells and terminal levels. In particular, it is known that serotoninergic fibers from the raphe system project to the substancia nigra (SN) and that this modulation is behaviourally relevant. In the present work, the effect of exogenous NOCI injected into the SN upon DA and 5-HT levels have been analyzed by means of differential pulse voltammetry and nafion-carbon fiber microelectrodes. Electrophysiological monitoring of multicell activity was concomitantly performed with the same microsensor. It appeared that both levels of these biogenic amines were specularly altered, with possibly a driving influence of the DA activity upon the serotoninergic function(s).
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.
Mar 2019 DOI 10.14302/issn.2471-2140.jaa-19-2699
M.M. Masoud HassanCorresponding author
Molecular Biology Department, National Research Centre, El-Tahrir st., Dokki, Giza, Egypt.
Xanthine oxidase is a commercially important enzyme with wide area of medical applications to develop diagnostic kits. Xanthine oxidase was extracted, purified and characterized from sheep liver (SLXO). The purification procedure involved acetone precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 columns. The sheep liver xanthine oxidase was homogeneously purified 31.8 folds with 3.5 U/mg specific activity and 24.1% recovery. SLXO native molecular weight was 150 kDa and on SDS-PAGE appeared as single major band of 75 kDa representing a homodimer protein. Isoelectric focusing of the purified SLXO resolved into two closely related isoforms with pI values of 5.6 and 5.8. The apparent Km for xanthine oxidase at optimum pH 7.6 was found to be 0.9 mM xanthine. FeCl2 and NiCl2 increased the activity of SLXO, while CuCl2 and ZnCl2 were found to be potent inhibitors of the purified enzyme. Allopurinol inhibits SLXO competitively with one binding site on the purified molecule and Ki value of 0.06 mM.
Feb 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2581
Khan AshrafCorresponding author
Departments of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
We report the case of a 75 year-old female with past history of ampullary adenocarcinoma presenting with a rapidly enlarging breast mass, initially misclassified on fine needle aspiration as a probable sarcoma, which was ultimately diagnosed as melanoma on resection in the absence of a known cutaneous primary lesion. Next-generation sequencing (NGS) of the tumor revealed a mutation in the Smoothened oncogene (SMO) of unknown significance and wild-type BRAF. To our knowledge, SMO mutation in melanoma of any site has not been previously reported, though the effectiveness of SMO inhibitors has been studied in both in vivo and in vitro models of melanoma. Currently, these inhibitors have not been studied in SMO mutant melanoma. The patient declined further therapy after resection due to multiple comorbidities. She expired two years after presenting with the breast mass from complications of high grade urothelial carcinoma.
Feb 2019 DOI 10.14302/issn.2574-612X.ijpr-18-2564
Patel PritteshCorresponding author
C. G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Bardoli
The widely held belief that emotional and psychological processes affect our physical health, mental health and general well-being are central to a holistic view of the individual, and as such, it is a useful foundational concept in integrative medicine. The purpose of this paper is to review substantial amounts of the latest research and recent findings on this issue to enable us to throw some light on how inhibitory factors to emotional expression and experience can endanger our health, both physically and psychologically including our general wellbeing. In addition, the connection between repression of emotion and certain mental disorders like depression and scientifically proven healthy ways to manage issues bordering on emotion was outlined. The information contained in this paper is just as important to health care providers and also to the patients they deal with
Feb 2019 DOI 10.14302/issn.2578-8590.ipj-19-2623
Hinzpeter JaimeCorresponding author
Department of Orthopaedic Surgery, Clinical Hospital, University of Chile, Santos Dumontt # 999, Independencia, Zip Code: 8380456, Santiago, Chile.
Neosaxitoxin (NeoSTX) is a specific high-affinity inhibitor of voltage-dependent sodium channels, which has shown excellent results as a local anesthetic in various pathologies and post-operative protocols, since it effect is long-lasting and have virtually no side effects.The aim of this study was to analyze the effect of NeoSTX as an epidural anesthetic in female cats, undergoing ovariohysterectomy, compared to Lidocaine in a randomized and double-blind study. Two groups of 11 female cats were randomly in the NeoSTX group and the lidocaine group. They were administered, respectively, a single dose of NeoSTX (0.5 μg / kg) or lidocaine (4 mg / kg, 2%) by epidural via. Using the UNESP-Botucatu pain assessment scale, which considers multiple behavioral and physiological factors, the epidural anesthetic effect of NeoSTX and lidocaine was evaluated, up to 240 min after the ovariohysterectomy procedure. NeoSTX no altered the peripheral blood pressure during the cut of uterine cervix, and generated lower values on the pain scale as compared to the lidocaine treatment. None of the cats anesthetized with NeoSTX required an extra dose of pain-relieving drugs (2 mg / kg of tramadol) during the first 150 min after surgery, whereas nine cats from the lidocaine group did need an extra dose of analgesic. NeoSTX is a powerful pain blocker, with a long-lasting anesthetic effect when administered by an epidural procedure. Therefore, NeoSTX emerges as a promising alternative to conventional anesthetics for the treatment of postoperative pain.
Jan 2019
Excessive variability in behavioral performance and neuronal activation is a common finding in studies of schizophrenia. Recent evidence suggests that this may be due to an imbalance in the ratio of excitation to inhibition in brain function, or E/I imbalance. We used computational modeling of visual system activity to determine whether different potential causes of E/I imbalance would generate effects resembling those reported in schizophrenia. Three major findings emerged. First, reductions in retinal and lateral geniculate nucleus signaling initially led to increases in firing rate variability within the context of reduced V1 activation; however, with prolonged adaptation to weakened sensory signaling, compensatory hyper-activation in V1 neurons occurred, but variability was no longer increased. Second, direct increases in V1 excitation, or decreases in inhibition, led to the highest levels of initial activation but not variability; however, with prolonged inhibitory adaptation to increased excitation, overall activity was no longer elevated, but an increase in firing rate variability was observed. Third, the greatest fluctuation in firing rate variability, in response to the same stimulus across increasing contrast levels, was observed with reductions in sensory signaling, but only immediately after model perturbations; with prolonged adaption, the largest fluctuations were associated with increased excitation or reduced inhibition within V1. Implication of these findings are that schizophrenia-related increases in neuronal response variability may arise from at least two sources: 1) weakened sensory signaling and its associated low signal-to-noise ratio; and 2) compensatory but incomplete inhibitory responses to continuous increases in cortical excitation.
Jan 2019 DOI 10.14302/issn.2639-3166.jar-18-2502
Campbell MichaelCorresponding author
Lake Erie Regional Grape Research and extension Center, 662 North Cemetery Road, North East, PA 16428
The compound 1,4-dimethylnaphthalene, originally isolated from dormant potatoes, is currently in use as a commercial sprout inhibitor. Growers and processors report a reduction in fungal infections in potatoes treated with DMN resulting in increased yields. To assess the effects of DMN on fungal growth a culture of Fusarium oxysporum was isolated from potato tubers and identified via DNA fingerprinting using the 18ITS ribosomal region. Growth of F. oxysporum was inhibited by 31% after four days of exposure to DMN but overall rate of spore germination was not affected by DMN treatment. The growth of additional fungi, including Alternaria alternata, Aspergillus niger, Epicoccum nigrum, Gnomoniopsis smithogilvyi, Phoma medicaginis, and Pythium ultimum was inhibited by DMN as was suppression of sporulation in A. niger. These results suggest that DMN is fungistatic at the application levels examined.
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.
Oct 2018 DOI 10.14302/issn.2577-2279.ijha-18-2407
Fu HuiCorresponding author
Shenzhen Institute of Wuhan University, Shenzhen, china.
Oligodendrocytes are specialized glial cell in central nervous system (CNS) responsible for the formation of myelin sheath around the axon. Oligodendrocyte proliferation and differentiation is regulated by Wnt signaling pathway, at various stages. However, different study groups have described controversial conclusions about the effect of Wnt on oligodendrocytes precursor cells (OPCs) development. Initially it has been proposed that Wnt pathway negatively regulates the OPCs proliferation and differentiation but recently some studies have described that Wnt promotes the differentiation of OPCs. After carefully reviewing the literature, we believe that Wnt play multiple roles in OPCs differentiation and its function is time (stage) and dose sensitive. Low to moderate activation of Wnt promotes OPC development, while too much or too low is inhibitory. Current evidences also suggested that in early developmental stages, Wnt inhibits the OPCs formation from neural progenitors and differentiation into immature oligodendrocytes. But in late stages Wnt plays promoting role in differentiation and maturation of oligodendrocytes. This review summarized the updated information regarding the critical role of Wnt signaling cascade in proliferation and differentiation of OPCs.
Aug 2018 DOI 10.14302/issn.2639-1716.jn-18-2208
J. Mizejewski GeraldCorresponding author
Wadsworth Center, New York State Department of Health, PO Box 509, Empire State Plaza, Albany, NY 12201-0509
Breast cancer (BC) is the leading cause of cancer-related deaths in young to middle-aged women worldwide. Moreover, the survival rate in BC-patients is only 20% when associated with metastatic disease. The high mortality rate observed in BC women with metastatic disease has precipitated a major challenge revealing an unmet need to develop new therapeutic strategies in treating metastatic cancer. One such approach has involved utilization of chemokines and their receptors as therapeutic targets for cancer metastasis. It has been established that a definitive correlation exists between overexpressed CXCR4 malignant cell receptors and cancer cell growth, invasion, and migration. It is also widely accepted that the CXCR4 receptor, complexed to its CXCL12 ligand, plays a major role in establishing migratory pathway gradients for cancer cells migrating to distant tissues/organ sites. It would follow that chemokine decoy ligands, such as peptide antagonists and inhibitors, could serve to induce receptor blockade and impede subsequent intracellular signaling. Such ligands, synthetic and natural, reportedly contribute to reducing cancer cell growth, invasion, adherence, and migration. The present commentary describes several existing synthetic CXCR4 receptor-ligand peptide antagonists and presents a strategy to develop naturally-occurring human protein-derived peptide candidates.
May 2018 DOI 10.14302/issn.2832-5311.jpcd-18-2077
Farkaš VladimírCorresponding author
Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, 84538 Bratislava, Slovakia
Polysaccharide transglycosylases (PTGs) are a unique group of glycoside hydrolases playing important roles in the formation and modification of plant and fungal cell walls. Their action involves cutting the molecule of the polysaccharide substrate at the glycosidic bond, followed by transfer of the newly formed reducing-end fragment to the non-reducing end of another polysaccharide molecule, with the formation of a new glycosidic bond. As there is no net increase in the number of reducing ends in the system, conventional reductometric methods used to assess the activity of glycoside hydrolases are ineffective. Since the PTGs participate in vital processes, such as the elaboration of cell walls in plants and fungi, and are not present in animal cells, they are considered as possible targets for future specific fungicides and herbicides. Biochemical studies of PTGs, as well as the search for their inhibitors, require the availability of convenient and efficient methods for their assay. In this review we briefly describe the principles of methods used to detect and to determine the activity of this important group of enzymes.
Nov 2017 DOI 10.14302/issn.2576-9383.jhhr-17-1768
Yassin Ibrahim SaharCorresponding author
Botany Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt.
Antifungal antagonism of different fourteen plant essential oils was examined as natural agents against economic and hygienic effective three yeasts; the preservative efficacy of most potent anti-yeast essential oil in food sanitary was also tested. Study involved oils antifungal bioactivity screening against Saccharomycescerevisiae, Candida albicans,and Candida utilis. Study also included selection and invitro extraction of most bioactive oil, and evaluation of its antifungal minimal inhibitory concentrations (MICs). Control ofjuice spoilage by Saccharomycescerevisiae under the effect of in vitro oil extract different concentrations was also screened. Among the tested essential oils, apricot seed oil was the most bioactive anti-yeast agent. Two MIC values of apricot oil invitro extract, 12.5μgml-1 and 25μgml-1 were recorded. In juice samples, oil extract bioactivity increased gradually up to concentration 100μgml-1.Highest oil preservative ability was observed at oil concentration of and above 125μgml-1. Higher oil concentrations needed for juice preservation were found more than in vitro assay to give the same effect. Applying of apricot oil and some other plant essential oils could be used as an environmental safety mode in osmophilic food preservation and in Candidate diseases biocontrol.
Nov 2017 DOI 10.14302/issn.2372-6601.jhor-17-1761
Lee Mortensen GitteCorresponding author
AnthroConsult, Fynsgade 24, 8000 Aarhus C, Denmark
With the introduction of tyrosine kinase inhibitors (TKI), patients with chronic myeloid leukemia (CML) have obtained survival rates close to normal. It may appear paradoxical, then, that medication adherence is suboptimal in some health care settings. As the first of its kind, this study aimed to explore drivers and barriers to TKI treatment adherence in Danish CML patients. A literature study informed the design of qualitative interviews with 20 patients, individually and in focus groups, focusing on their disease perceptions of CML, their health-related quality of life (QoL) and medication adherence. The study showed that many participants had previously switched treatment due to lacking efficacy or intolerance but most felt their current disease burden was tolerable. Anxiety might, however, resurface if treatment stopped working or with the occurrence of infections or side effects, creating a state of ‘fragile peace’. To these patients, their role functioning – as professionals, spouses, parents and grandparents – was crucial to uphold a positive self-image and meaningful life. Whether treatment enabled or hindered this was thus decisive to their QoL and medication adherence. Our participants expressed high adherence rates with only one having intentionally non-adhered due to side effects and poor QoL. Most participants felt well-informed about CML and treatment and privileged to receive specialised personal care from the public health care system acting to motivate their medication adherence. As a novel finding, this study indicates that the prospect of treatment-free remission may positively affect ‘adherence’ suggest this should be explored in future studies.
Aug 2017
B Huang DavidCorresponding author
Motif BioSciences, New York, New York,
Iclaprim is a novel bacterial dihydrofolate reductase inhibitor in Phase 3 clinical development for the treatment of acute bacterial skin and skin structure infections and hospital acquired bacterial pneumonia caused by Gram-positve bacteria. Daptomycin, linezolid and vancomycin are commonly used antibiotic for these indications. With increase selective pressure to these generic antibiotics, outbreaks of bacterial resistance to these antibiotics have been reported. This in vitro study evaluated the activity of iclaprim against methicillin-resistant Staphylococcus aureus (MRSA) isolates, which were also not susceptible to daptomycin, linezolid or vancomycin. Iclaprim had an MIC ≤1 µg/ml to the majority of MRSA isolates that were nonsusceptible to daptomycin (5 of 7 71.4%), linezolid (26 of 26 100%), or vancomycin (19 of 28 66.7%). In time-kill curves analyses, iclaprim demonstrated ≥3 log10 reduction in CFU/mL at 4-8 hours for tested strains and isolates nonsusceptible to linezolid or vancomycin. Together these data support the use of iclaprim in serious infections caused by MRSA nonsusceptible to daptomycin, linezolid or vancomycin.
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.
Apr 2017 DOI 10.14302/issn.2372-6601.jhor-17-1463
Szablewska SylwiaCorresponding author
Nicolaus Copernicus University, Faculty of Health Sciences; Department of Oncology, Radiotherapy and Ginecologic Oncology, Poland
Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells. In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment. In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.
Jun 2016 DOI 10.14302/issn.2572-5424.jgm-16-1028
H Baslow MorrisCorresponding author
Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
N-acetylaspartylglutamate (NAAG) is the highest concentration dipeptide present in brain. It is found primarily in neurons but its function is unclear. NAAG is synthesized by neurons from N-acetylaspartate and glutamate (Glu), maintained at mM concentrations and is released non-synaptically to extracellular fluid (ECF). NAAG is a non-excitatory form of Glu, and is targeted to the metabotropic group II Glu receptor 3 (mGluR3) on the surface of astrocytes. After docking with the receptor, Glu is released by the action of NAAG peptidase. Previously, it was shown for the first time that an NAAG-peptidase inhibitor reduced global cerebral blood flow (CBF) in mouse brain but did not affect their physical performance. Recently, it has been demonstrated that there are two separate systems involved in neurovascular coupling by astrocytes, one is a rapid focal phasic response providing energy for stimulation-induced neuronal activity, and the other a slower global tonic response providing energy for ongoing metabolic activities. Many neurovascular coupling mechanisms are known that regulate phasic changes in CBF, but how the brain accomplishes tonic control is unknown. In this paper we bring together two separate lines of inquiry, the decades’ long search for the function of NAAG, and the more recent search for the mechanism of tonic neurovascular control. Herein, we present evidence that NAAG is the neurovascular coupling agent that regulates tonic changes in CBF via the astrocyte mGluR3-NAAG peptidase connection.
May 2016 DOI 10.14302/issn.2470-5020.jnrt-15-908
Kaya YaseminCorresponding author
Ordu University Medical School, Department of Internal Medicine, Ordu, Turkey
Objective: We aimed to investigate homocysteine levels and carotid intima-media thickness (CIMT) in Parkinson’s Disease (PD), to determine relationship of these parameters and as well as to determine whether CIMT in patients with PD was associated to age, disease duration, age of disease onset, stage, the Unified Parkinson Disease rating scale (UPDRS), the drugs used in therapy. Methods: The study population consisted of 55 PD patients (37 male) and 25 healty subjects. The severity of neurological impairment was assessed with UPDRS and the Hoehn-Yahr scale. CIMT and homocysteine levels were measured. Anti-parkinsonian treatments were recorded and the total daily dose of levodopa was calculated for each patient. Results: Homocysteine levels were significantly higher in the patient group compared to the control group (p=0.002). A positive correlation was found between CIMT and homocysteine (r=0.29 p=0.03), but no a relationship between CIMT and UPDRS scores, disease duration, age of disease onset, and stage. Mean levodopa dosage did not predict CIMT 0.6 mm (AUC: 0.546, 95%CI 0.372-0.720, p=0.59). Homocysteine 14 µmol/l predicted CIMT 0.6 mm with 64% sensitivity and 69% specificity (AUC: 0.654, 95%CI 0.488-0.819, p=0.07). Dıscussion: This study revealed that homocysteine levels in levodopa + dopa decarboxylase enzyme inhibitor (DDEI) group were increased which was correlated with a mild increasement of CMIT. This might indicate to the importance of clinical and radiological follow up of PD patients who are under treatment of levodopa + DDEI. Conclusion: Our Findings May Suggest The Role Of CIMT As A Meaningful Clinical Marker For Follow-Up Of Patients With PD
Feb 2016 DOI 10.14302/issn.2574-4488.jna-15-712
Bernieh BassamCorresponding author
Nephrology, Department of Internal Medicine, Tawam Hospital, Al-Ain, United Arab Emirates.
Background Dapagliflozin; the new oral hypoglycemic agent; is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that acts by inhibiting glucose reabsorption in the proximal tubule of the nephron. Main reported side effects are osmotic diuresis, dehydration, urinary tract and genital infections. Here, we report a case of acute bilateral hydronephrosis after the introduction of dapagliflozin. Case Presentation A 52 year old nurse lady, with 15 year history of type2 diabetes mellitus (T2 DM) complicated by type4-renal tubular acidosis, hypertension, proteinuria, and hyperlipidemia. Patient had two episodes of UTI’s in 2011 required full urologic work up, were successfully treated with simple courses of oral antibiotics. CT pyelography done in 2011 was normal. Dapagliflozin was added to her therapeutic regimen in March 2015. Results Within 48 hours after starting dapagliflozin, she reported increased urine output. Ten days later; she developed severe bilateral loin and lower back pain, followed by suprapubic pain, dysuria and fever. Urine analysis and cultures confirmed E. coli urosepsis. Renal US revealed echogenic kidneys with 12 mm bilateral hydronephrosis, normal ureters and urinary bladder. Discontinuation of dapagliflozin in April 2015 resulted in resolution of symptoms. Repeat CT of the abdomen in July 2015 revealed no hydro nephrosis. Conclusions This is the first case report of reversible bilateral hydronephrosis after the use of dapagliflozin. The cause of hydronephrosis, could be explained by over-diuresis and/or by the unmasking of underlying subclinical obstruction in both uretero-pelvic junctions (UPJ).
Aug 2015 DOI 10.14302/issn.2372-6601.jhor-15-667
CL Jr CowanCorresponding author
Department of Ophthalmology, Washington, D.C. Veterans Administration Medical Center, Washington, D.C.
Trichomegaly is a known adverse effect with the epidermal growth factor receptor inhibitor (EGFRI) and prostaglandin analogue drug classes. We present a chronic Latanoprost user who developed symptomatic trichomegaly subsequent to initiating an EGFRI medication and believe this case offers evidence that the two classes of medications may cause a similar eyelash manifestation through different mechanisms.
Jan 2015 DOI 10.14302/issn.2471-7061.jcrc-14-394
C. Papagiorgis PetrosCorresponding author
Technological Educational Institute of Athens, Faculty of Health and Caring Professions
This review synthesizes evidence on NSAIDs and colorectal cancer prevention. It balances chemopreventive efficacy against gastrointestinal and cardiovascular risks, and considers selective COX‑2 inhibitors, dosing, and candidate populations for risk‑benefit.
Jan 2014 DOI 10.14302/issn.2328-0182.japst-12-183
D. Mahajan SupriyaCorresponding author
Department of Medicine, Division of Allergy, Immunology, and Rheumatology,
Gold nanorods (GNRs) are plasmonic nanostructures by virtue of their size-dependent optical properties, offer a bionanotechnology platform in areas of bioimaging, drug delivery etc for disease diagnosis, prognosis, and therapy. GNRs are more sensitive to changes in local environments, and offer strong scattering and absorption efficiencies thus providing opportunities to integrate multiple imaging modes and therapeutic strategies. The hydrodynamic size of these GNR under physiological condition is <100 nm, making them ideal as intracellular delivery agents. RNA interference using small inhibitory RNA (siRNA) has become a powerful tool to downregulate mRNA levels by cellular nucleases that become activated when a sequence homology between the siRNA and a respective mRNA molecule is detected. siRNA is used to silence genes involved in the pathogenesis of various diseases and holds a promising option for the development of novel therapeutic strategies in neurological dysregulation such as that observed in drug addiction. However, a major challenge in gene therapy continues to be effective delivery of siRNA and its sustained release at targeted sites. Previously, we have shown the GNR coated with poly (diallyldimethyl ammoniumchloride) (GNR-PDDAC) electrostatically complexed to the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) siRNA forming a GNR-nanoplex that was able to effectively silence the DARPP-32 gene expression in dopaminergic neuronal (DAN) cell cultures in- vitro. The current report, explores if modification of the surface coating properties of the GNRs with different surface coatings namely, amino terminated polyethylene glycol (GNR-PEG), polyethyleneimine (GNR-PEI) and Chitosan (GNR-CIT) alters their stability, cytotoxicity and DARPP-32 gene silencing efficiency in-vitro dopaminergic neuronal (DAN) cell cultures with the goal of determining the most suitable surface coating for the GNR that would provide a GNR-nanoplex with the most stability, least cytotoxicity and most efficacious gene silencing.
Nov 2013 DOI 10.14302/issn.2328-0182.japst-13-185
WS WaringCorresponding author
Acute Medical Unit, York Hospital, York, UK
Background: Antidepressant agents are commonly implicated in drug overdose, and the toxicological profile varies between agents. Clinical data concerning overdoses are not systematically sought or evaluated in pharmacovigilance. The present study sought to examine the feasibility of collecting Emergency Department data concerning antidepressant overdose. Methods : Presentations to York Hospital due to intentional antidepressant overdose were studied between 2010 and 2011. Data collected were the type of antidepressant, dose, co-ingested drugs, duration of hospital stay, and need for critical care. Community National Health Service prescription data were evaluated across York and North Yorkshire region. Results : There were 250 overdose episodes. These involved a selective serotonin reuptake inhibitor (SSRI) in 183 (73.2%), and a tricyclic in 45 (18.0%), equivalent to 24 episodes per 100,000 prescription items (95% CI 21-28 per 100,000) and 11 per 100,000 (8-15 per 100,000) respectively (P<0.0001). Citalopram was the most commonly prescribed, and associated with 22 overdose episodes per 100,000 (17-27 per 100,000). Fluoxetine was associated with 32 overdose episodes per 100,000 (24-41 per 100,000) (P=0.032 versus citalopram), whereas the lower rates were observed for amitriptyline (13, 9-17 per 100,000) (P=0.004) and dosulepin (2, 0-10 per 100,000) (P=0.001). Conclusions : A higher than expected number of overdose episodes involved an SSRI based on National Health Service primary care prescribing, and fewer episodes involved a tricyclic antidepressant. Clinical outcomes differed between agents, indicating the feasibility of using Emergency Department data to detect different patterns of toxicity between antidepressants. Further work is required to examine whether systematic collection of clinical toxicology data might enhance existing pharmacovigilance systems.
Sep 2013 DOI 10.14302/issn.2326-0793.jpgr-13-257
O’Connell KathleenCorresponding author
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC,
Lapatinib, a small molecule tyrosine kinase inhibitor is currently used in the treatment of HER2-positive breast cancer. The aim of this study was to further understanding of lapatinib response for the development of novel treatment lapatinib-focussed treatment strategies. HER2-overexpressing SKBR3 breast cancer cells were treated with lapatinib for 12 hours and the resultant proteome analyzed by a comprehensive ion-current-based LC-MS strategy. Among the 1224 unique protein identified from SKBR3 cell lysates, 67 showed a significant change in protein abundance in response to lapatinib. Of these, CENPE a centromeric protein with increased abundance, was chosen for further validation. Knockdown and inhibition of CENPE demonstrated that CENPE enhances SKBR3 cell survival in the presence of lapatinib. Based on this study, CENPE inhibitors may warrant further investigation for use in combination with lapatinib.