Effect of doxorubicin on Bcl2 and Bax expression in Rat heart

Background and Objective: The anthracyclin drug doxorubicin (Adriamycin) is one of the most effective antineoplastic agents, and widely used to treat a number of malignancies. However, its use has been restricted due to the dose-dependent cardiotoxicity. The mechanisms of Doxorubicin - induced cardiotoxicity is not entirely clear. This study investigates the effect of Doxorubicin on Bcl2 and Bax genes expression as key molecules that involve in intrinsic pathway of apoptosis in rat heart. Materials and Methods: In this experimental study Doxorubicin administration, male Wistar rats were exposed to intraperitoneal injections (2.5 mg/kg, six times for 2 weeks, n=20). Animals were randomly assigned to the healthy untreated control (n=10) and to the Doxorubicin treatment groups (n=10). Three weeks after completion of treatment myocardial fibrosis, Bcl2 and Bax genes expression were investigated by Masson’s trichrome staining and Real Time- PCR analysis respectively. Statistical analysis was performed using the SPSS-16 and independent samples t-test, Mann-Whitney and Kaplan-Meyer method. Results: Masson’s trichrome staining showed that Doxorubicin increased fibrosis in the cardiac muscle (16.4±1) in compare to control group (1±0.79). Real Time- PCR analysis showed that Doxorubicin decreased Bcl2 expression levels (0.1±0.07) and increased Bax expression levels (2.1±0.1) in the myocardium in compare to control group (P<0.01). Conclusion: This study showed that administration of Doxorubicin increase interstitial fibrosis of myocardium and Bax expression levels and decrease Bcl2 expression that are the key genes of mitochondria-dependent apoptotic pathway

An intervention to increase hepatitis C virus diagnosis and treatment uptake among people in custody in Iran

Background: Iran is among countries with high opioid agonist therapy (OAT) coverage in prisons, which provides an infrastructure to increase feasibility of HCV programs. We aimed to evaluate the impact of an intervention to improve HCV screening, diagnosis, and treatment, including alongside the provision of OAT, in an Iranian prison. Methods: During July-December 2018, in the Gorgan prison, all incarcerated adults (>18 years) received HCV antibody rapid testing and, if positive, provided a venepuncture sample for HCV RNA testing. Participants with positive RNA received direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir) for 24 or 12 weeks, respectively, for those with and without cirrhosis. Response to treatment was measured by the sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 2015 incarcerated people with a median age of 35 years (IQR:29�41), the majority were male (97%), had not finished high school (68%), and had a history of drug use (71%), of whom 15% had ever injected drugs. A third of participants were receiving OAT, including 54% of those who had ever injected. HCV antibody prevalence was 6.7%, and RNA was detected in 4.6% of all participants; this prevalence was 32.6% and 24.7% among those with a history of injection, respectively. Treatment uptake was 82% (75/92) and was similar among people on OAT and those with a history of injection (81%). The majority completed treatment in prison and were available for SVR12 assessment (71%, 53/75). Achieved SVR12 was 100% (53/53) based on the available case analysis; those who did not have available SVR12 were released either prior to treatment initiation or completion (n = 39). Conclusion: The availability of OAT infrastructure should be considered as an opportunity for enhancing HCV care in prisons. Where resources are limited, the prison harm reduction network could be used to design targeted HCV programs among people who are at higher risk of infection. © 2021 Elsevier B.V

Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease

Despite substantial clinical advances over the past 65 years, cardiovascular disease remains the leading cause of death in America. The past 15 years has witnessed major basic and translational interest in the use of stem and/or precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells (MSCs) are widely studied and in early stage clinical studies show promise for repair and regeneration of cardiac tissues. The ability of MSCs to differentiate into mesoderm and non-mesoderm derived tissues, their immunomodulatory effects, their availability and their key role in maintaining and replenishing endogenous stem cell niches have rendered them one of the most heavily investigated and clinically tested type of stem cell. Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. Here, we review the biology of MSCs, their interaction with endogenous molecular and cellular pathways, and their modulation of immune responses. Additionally, we discuss factors that enhance their proliferative and regenerative ability and factors that may hinder their effectiveness in the clinical setting

Decomposing socioeconomic inequality in dental caries in Iran: Cross-sectional results from the PERSIAN cohort study

Background: The current study aimed to measure and decompose socioeconomic-related inequalities in DMFT (decayed, missing, and filled teeth) index among adults in Iran. Methods: The study data were extracted from the adult component of Prospective Epidemiological Research Studies in IrAN (PERSIAN) from 17 centers in 14 different provinces of Iran. DMFT score was used as a measure of dental caries among adults in Iran. The concentration curve and relative concentration index (RC) was used to quantify and decompose socioeconomic-related inequalities in DMFT. Results: A total of 128,813 adults aged 35 and older were included in the study. The mean (Standard Deviation SD) score of D, M, F and DMFT of the adults was 3.3 (4.6), 12.6 (10.5), 2.1 (3.4) and 18.0 (9.5), respectively. The findings suggested that DMFT was mainly concentrated among the socioeconomically disadvantaged adults (RC = - 0.064; 95% confidence interval CI), - 0.066 to - 0.063). Socioeconomic status, being male, older age and being a widow or divorced were identified as the main factors contributing to the concentration of DMFT among the worse-off adults. Conclusions: It is recommended to focus on the dental caries status of socioeconomically disadvantaged groups in order to reduce socioeconomic-related inequality in oral health among Iranian adults. Reducing socioeconomic-related inequalities in dental caries should be accompanied by appropriate health promotion policies that focus actions on the fundamental socioeconomic causes of dental disease. © 2020 The Author(s)

Epigenetic reprogramming converts human Wharton's jelly mesenchymal stem cells into functional cardiomyocytes by differential regulation of Wnt mediators

BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations. We characterized for cardiogenic differentiation by assessing the expression of cardiac-specific markers by immunolocalization, quantitative RT-PCR, and flow cytometry. Cardiac functional studies were performed by FURA2AM staining and Greiss assay. The role of Wnt signaling during cardiac differentiation was analyzed by quantitative RT-PCR. In-vivo studies were performed in a doxorubicin-induced cardiotoxic mouse model by injecting cardiac progenitor cells. Promoter methylation status of the cardiac transcription factor Nkx2.5 and the Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), after cardiac differentiation was studied by bisulfite sequencing. RESULTS: By induction with DC301 and DC302, WJMSCs differentiated into cardiomyocyte-like structures with an upregulation of Wnt antagonists, sFRP3 and sFRP4, and Dickkopf (Dkk)1 and Dkk3. The cardiac function enhancer, vinculin, and DDX20, a DEAD-box RNA helicase, were also upregulated in differentiated cardiomyocytes. Additionally, bisulfite sequencing revealed, for the first time in cardiogenesis, that sFRP4 is activated by promoter CpG island demethylation. In vivo, these MSC-derived cardiac progenitors could not only successfully engraft to the site of cardiac injury in mice with doxorubicin-induced cardiac injury, but also form functional cardiomyocytes and restore cardiac function. CONCLUSION: The present study unveils a link between Wnt inhibition and epigenetic modification to initiate cardiac differentiation, which could enhance the efficacy of stem cell therapy for ischemic heart disorders