Journal of Research in Medical Sciences1735-19953169202609021176111761EN20260902<p><strong>Background:</strong> Gut microbiota play an important role in bilirubin metabolism and may influence the course of neonatal physiological jaundice. This systematic review and meta?analysis aimed to evaluate the strain?specific efficacy of probiotics in the prevention and adjunctive treatment of neonatal physiological jaundice.</p><p><strong> Materials and Methods:</strong> A comprehensive search of PubMed, Scopus, Embase, Web of Science, Google Scholar, Cochrane Library, World Health Organization databases, and Persian databases (Scientific information database [SID] and Magiran) for studies  ublished up to 2024 was conducted. Randomized controlled trials (RCTs) evaluating probiotics in term and late?preterm neonates (?35 weeks) with physiological jaundice were included. Data extraction, quality assessment, and meta?analysis were performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta?analyses guidelines using a random?effects model.</p><p><strong>Results:</strong> Nineteen RCTs (13 therapeutic and 6 prophylactic) were included. Prophylactic probiotic administration was associated with a reduced need for phototherapy (odds ratio [OR] =0.60; 95% confidence interval [CI]: 0.37–0.96). As an adjunct to phototherapy, probiotics were associated with lower bilirubin levels (mean difference [MD] = ?1.61; 95% CI: ?3.10–?0.11), shorter phototherapy duration (~5 h), and reduced  hospitalization (0.3 days). Reduction in bilirubinw was more evident during the 2nd and 3rd days of treatment. Strain?specific differences were observed; Clostridium butyricum and Lactobacillus reuteri demonstrated larger pooled effect sizes for bilirubin reduction, whereas Saccharomyces boulardii showed greater<br />protective effect against phototherapy.</p><p><strong> Conclusion:</strong> Probiotics may serve as beneficial adjuncts in the prevention and management of neonatal physiological jaundice, with potential strain?dependent differences. Given heterogeneity and limited data for some strains, findings should be interpreted cautiously. Further well?designed, adequately powered RCTs are warranted.<br /><br /></p>http://jrms.mui.ac.ir/index.php/jrms/article/view/11761http://jrms.mui.ac.ir/index.php/jrms/article/download/11761/6530

Journal of Research in Medical Sciences1735-19953169202609021176311763EN20260902<p><strong>Background:</strong> Ranked as the fifth leading global health burden in 2022, diabetes mellitus is the driver of diabetic kidney disease (DKD), a condition responsible for nearly half of end?stage kidney disease cases. Despite its significant impact, therapeutic progress in DKD is hindered by an incomplete understanding of the underlying cell?specific molecular mechanisms.</p><p><strong> Materials and Methods:</strong> Single?cell RNA sequencing data (GSE183276) from the kidney precision medicine project, including kidney samples from 20 healthy  individuals and 14 DKD patients, were obtained. After quality control, batch effect correction, and cell type annotation, cell type?specific differentially expressed genes were identified. Enrichment analyses were performed using WebGestalt. Trajectory inference was conducted to characterize dynamic cellular states. Finally, DrugTar, a previously developed deep learning tool, was applied to identify the most druggable genes.</p><p><strong> Results:</strong> Among the 22 annotated cell types, collecting duct principal cells exhibited the largest number of differentially expressed genes, even after adjustment for cell abundance. This finding was also observed in an independent human kidney single?cell RNA?seq dataset (GSE211785), suggesting that this cell type experiences a profound transcriptional reprogramming in response to a diabetic milieu. Notably, trajectory analysis revealed distinct transcriptional states within principal cells, with mitochondrial metabolic processes being enriched across these subpopulations. Furthermore, a list of the most druggable genes is proposed as potential candidates for targeted delivery to principal cells.</p><p>Zahra Hamidifarid1,2, Yousof Gheisari1,2 This study underscores the significant transcriptional reprogramming of principal cells in DKD pathogenesis, a phenomenon that has rarely received attention in previous works. These cells can be considered as candidates in strategies aimed at targeted drug delivery for DKD.</p>http://jrms.mui.ac.ir/index.php/jrms/article/view/11763http://jrms.mui.ac.ir/index.php/jrms/article/download/11763/6532

Journal of Research in Medical Sciences1735-19953169202609021176411764EN20260902<p><strong>Background:</strong> Evidence on depressive symptoms and skeletal health is largely cross-sectional and rarely addresses competing risk, dose-response, or potential behavioral pathways. We examined the association between baseline depressive symptoms and incident osteoporosis in older adults, accounting for competing mortality and exploring mediation by physical activity.</p><p><strong>Materials and Methods:</strong> We analyzed 4920 adults aged ? 60 years from the English Longitudinal Study of Ageing with Wave 1 8?item Center for Epidemiologic Studies Depression Scale (CES?D?8) scores and follow?up osteoporosis ascertainment. Incident<br />physician?diagnosed osteoporosis was the outcome. Cox models estimated hazard ratios (HRs) per 1?point higher CES?D?8 score. Restricted cubic splines assessed dose?response, Fine–Gray models accounted for death as a competing event, and exploratory  atural?effects models assessed baseline physical activity as a potential mediator.</p><p><strong>Results:</strong> During a median follow?up of 16.0 years, 502 participants developed incident osteoporosis and 1138 deaths occurred. Higher CES?D?8 scores were associated with greater<br />osteoporosis risk in the fully adjusted Cox model (HR, 1.05; 95% confidence interval [CI], 1.01–1.10; P = 0.020), with consistent results in Fine–Gray models (subdistribution HR, 1.05; 95% CI, 1.01–1.10; P = 0.019). The dose–response appeared approximately<br />linear. Exploratory subgroup analyses did not show robust effect modification, and mediation by baseline physical activity was not statistically supported.</p><p><strong> Conclusion:</strong> Baseline depressive symptoms were associated with a small increase in incident osteoporosis risk among older adults. The individual?level effect size was modest, and mediation findings should be interpreted as exploratory<br />rather than causal.</p>http://jrms.mui.ac.ir/index.php/jrms/article/view/11764http://jrms.mui.ac.ir/index.php/jrms/article/download/11764/6533

Journal of Research in Medical Sciences1735-19953169202609021176011760EN20260902The interplay between sympathetic nervous system activation and metabolic disorders, particularly type 2 diabetes mellitus (T2DM) and hypertension, has been increasingly recognized as a critical factor in cardiovascular morbidity and mortality. This review<br />explores the potential mechanisms linking sympathetic overactivity to insulin resistance (IR) and T2DM, highlighting the role of renal denervation (RDN) as a promising  therapeutic intervention. Sympathetic activation contributes to metabolic dysregulation<br />by increasing plasma fatty acids, enhancing hepatic gluconeogenesis, and impairing pancreatic insulin release, while also inducing vasoconstriction and reducing glucose uptake in skeletal muscle. RDN, a catheter?based procedure targeting renal sympathetic<br />nerves, has shown efficacy in managing resistant hypertension and improving glucose metabolism by reducing sympathetic drive, normalizing hepatic gluconeogenesis gene expression, and enhancing insulin sensitivity. Experimental and clinical studies suggest that RDN may mitigate IR, improve glycemic control, and reduce renal complications in diabetic models, independent of obesity or glucose tolerance status. However, the long?term effects on glycemic control and broader clinical applicability require further investigation.<br /><br />http://jrms.mui.ac.ir/index.php/jrms/article/view/11760http://jrms.mui.ac.ir/index.php/jrms/article/download/11760/6529

Journal of Research in Medical Sciences1735-19953169202609021176211762EN20260902Orofacial clefts (OFCs) are among the most common congenital anomalies, arising from a complex interplay of genetic and environmental factors that disrupt the precisely coordinated processes of craniofacial development. This review collects current evidence on the role of the chromodomain helicase DNA?binding (CHD) family of ATP?dependent chromatin remodelers in OFC etiology. We highlight the functions of the nine mammalian CHD proteins (CHD1–CHD9) during palatogenesis. There is strong evidence that mutations in CHD1, CHD3, CHD4, and CHD7 are directly causative for OFCs, frequently through alterations in critical developmental signaling pathways, including bone morphogenetic protein, wingless?related integration site, and retinoic acid, leading to disrupted cranial neural crest cell specification, migration, and differentiation. This review concludes that a specific subset of CHD proteins acts as essential epigenetic regulators of gene programs critical for palate formation. Understanding their<br />distinct and overlapping functions provides novel insights into OFC pathogenesis.<br /><br />http://jrms.mui.ac.ir/index.php/jrms/article/view/11762http://jrms.mui.ac.ir/index.php/jrms/article/download/11762/6531