Protein interaction mapping related to to becker muscular dystrophy

Objective Becker Muscular Dystrophy (BMD) is a neuromuscular disorder which is incurable. In this research protein interaction network of most associated proteins with BMD to provide better clarification of disorder underlying mechanism was investigated. Materials & Methods The related genes to BMD were retrieved via string database and conducted by Cytoscape and the related algorithms. The network centrality analysis was performed based on degree, betweenness, closeness, and stress parameters. Gene ontology and clustering were performed via ClueGO analysis. Results DMD as the super-hub as well as other central proteins including UTRN, TTN, DNM2, and RYR1 are important in BMD in terms of interactive features. The impairment of muscular contraction may be vital in BMD disease pathogenesis as it is the highlighted biological process term obtained by ClueGO analysis. Conclusion DMD targeting may be the main concern for dystrophy clinical approaches. However, the other suggested proteins should be evaluated. Targeting these key proteins are required for treatment goals following extensive validation studies. © 2019, Iranian Child Neurology Society. All rights reserved

Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats� hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development. © 2015, Springer Science+Business Media New York

Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured cochlea through PI3K/AKT pathway

Objective: Over 5 of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell-based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT dependent mechanism. Materials and Methods: Mesenchymal stem cells were treated with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- α (HIF-1α) and CXCR4 gene and protein expression was evaluated by RT- PCR and Western blot analysis. For in vivo assay, rats were assigned to control, sham, noise exposure groups without any treatment or receiving normal, DFO-treated and DFO +LY294002 (The PI3K inhibitor)-treated MSCs. Following chronic exposure to 115 dB white noise, MSCs were injected into the rat cochlea through the round window. Number of Hoechst- labelled cells was determined in the endolymph after 24 hours. Results: Deferoxamine increased P-AKT, HIF-1α and CXCR4 expression in MSCs compared to non-treated cells. DFO pre-conditioning significantly increased the homing ability of MSCs into injured ear compared to normal MSCs. These effects of DFO were blocked by LY294002. Conclusions: Pre-conditioning of MSCs by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI3K/AKT pathway activation. © 2018 John Wiley & Sons Lt

Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured cochlea through PI3K/AKT pathway

Objective: Over 5 of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell-based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT dependent mechanism. Materials and Methods: Mesenchymal stem cells were treated with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- α (HIF-1α) and CXCR4 gene and protein expression was evaluated by RT- PCR and Western blot analysis. For in vivo assay, rats were assigned to control, sham, noise exposure groups without any treatment or receiving normal, DFO-treated and DFO +LY294002 (The PI3K inhibitor)-treated MSCs. Following chronic exposure to 115 dB white noise, MSCs were injected into the rat cochlea through the round window. Number of Hoechst- labelled cells was determined in the endolymph after 24 hours. Results: Deferoxamine increased P-AKT, HIF-1α and CXCR4 expression in MSCs compared to non-treated cells. DFO pre-conditioning significantly increased the homing ability of MSCs into injured ear compared to normal MSCs. These effects of DFO were blocked by LY294002. Conclusions: Pre-conditioning of MSCs by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI3K/AKT pathway activation. © 2018 John Wiley & Sons Lt

General practitioners� knowledge and clinical practice in management of people with type 2 diabetes in Iran; the impact of continuous medical education programs

Background: To obtain information related to the knowledge and clinical practice of general practitioners (GPs) in management of people with type 2 diabetes, and to explore the impact of formal continuous medical education (CME) programs. Methods: A total of 1104 GPs participated in a cross sectional survey related to diabetes management considering ADA/EASD consensus 2011 focused on demographic and background characteristics, diabetes related knowledge, and patient care. Fisher�s Exact and chi-square tests were used in the analysis of contingency tables. Results: The majority of the participants (83.9) worked in large cities and 39.8 had taken part in CME programs in diabetes management. Overall, 52 of the GPs knew the treatment goal for HbA1c. The rate was slightly higher for those taken part in CME (P = 0.003). Considering patient care, slightly more than half of the participants answered correctly to the questions on duration and distribution of physical activity, with no difference by taking part in CME programs. On average, 41.5 of the physicians selected metformin as the first OGLD for treatment of type 2 diabetes, and only 27.9 stated that they add basal insulin to OGLD if treatment failed. Conclusion: The results of this study provide the evidence that the knowledge and clinical practice of Iranian GPs in management of type 2 diabetes were not satisfactory. Furthermore, traditional CME programs in diabetes management were not effective in changing the GPs' clinical practice. Consequently, designing and implementing more effective strategies are necessary for improving patient health related outcomes. © 2015, Academy of Medical Sciences of I.R. Iran. All rights reserved

Elderberry diet ameliorates motor function and prevents oxidative stress-induced cell death in rat models of Huntington disease

Huntington's disease (HD) is an inherited neurodegenerative disorder which begins in the striatum and then spreads to other neural areas. Known as a progressive movement cognitive disorder, HD has no efficient therapy. Although the exact mechanism of HD is still unknown, several different etiological processes such as oxidative stress have been shown to play critical roles. Also, the current evidence indicates a strong correlation between immune activation and neural damage induced by neuroinflammatory and apoptotic agents in neurodegenerative disorders. Thus, natural products like Elderberry (EB) could be considered as a novel and potential therapeutic candidate for the treatment of this disease. In this study EB was added to the daily ration of ordinary rats for two months in order to ameliorate inflammatory and oxidative responses in rats injected with 3-nitropropionic acid (3-NP) in an experimental model of HD. Using Rotarod and electromyography setups, we showed that EB diet significantly recovered motor failure and muscle incoordination in 3-NP injected rats compared to the control group. Also, the molecular findings implied that EB diet led to a significant drop in 3-NP induced growth in caspase-3 and TNF-α concentration. The treatment also improved striatal antioxidative capacity by a significant reduction in ROS and a remarkable rise in GSH, which might be correlated with motor recovery in the tests. In sum, the findings demonstrate the advantages of EB treatment in the HD rat model with a score of beneficial anti-oxidative and anti-inflammatory effects. © 2021 Elsevier B.V

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65\ua0years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results: A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N\ua0=\ua0221), errors in the prescribed doses were the most frequent cause of inappropriate use (N\ua0=\ua055). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions: In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. © 2011 Nature America, Inc. All rights reserved

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Thrombosis and Hemostasi