👤 Senthilkumar Palaniappan

Obesity is a chronic disease caused by the accumulation of cholesterol, which often requires long-term management strategies, such as dietary changes, increased physical activity, and psychological support. Obesity associated neurobehavioral disorders are a growing global health concern, emphasizing the need for innovative therapeutic strategies. Our study evaluates the therapeutic efficacy of (Z)-1-(furan-2-yl)-N-(4-(2-nitrophenyl)-6-(p-tolyl)pyrimidin-2-yl)methanimine referred as BN3 derivative, in treating high-fat diet-induced metabolic and behavioral dysfunctions in a zebrafish model. The research focused on reducing oxidative stress, lipid accumulation, and neurobehavioral deficits, which are closely linked to obesity-related metabolic stress. In this study, zebrafish were divided into five separate experimental groups: control group, model of obesity caused by high-fat diets, BN3 (50 µM and 100 µM), and Positive Control (PC) Group treated with Lovastatin 100 µM. Initially, fish were fed a high-fat diet for 14 days and followed by 30 days of exercise and simultaneously administering BN3 treatments via oral gavage. Assessment of biochemical, histopathology, gene expression, and behavioral were carried out. The results indicated that BN3 treatment significantly decreased oxidative stress levels by enhancing the activity of four antioxidant enzymes (Superoxide Dismutase, Catalase, Glutathione Transferase and Glutathione Peroxidase). BN3 also decreased lipid accumulation as evidenced through histological staining analysis, and total cholesterol estimation. BN3 enhanced locomotion, social interaction, and exploratory behaviors, and reduced anxiety, with the 100 µM treatment group exhibiting the same results as the PC. Gene expression analysis indicates that BN3 is modulating pparγ, fas, pik3cd, src-3, and bdnf pathways (metabolic and neuroinflammation pathways). BN3 impacted these multiple metabolic and neurobehavioral impairments associated with obesity through a multisite treatment approach. BN3 demonstrates significant therapeutic potential, assuring further studies to explore its long-term safety, pharmacokinetics, and translational application in managing obesity and related disorders. Show less

17β-Hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiency is a rare 46XY disorder of sex development (DSD) of androgen biosynthesis. We aimed to describe the complexities in diagnosis, gender assignment, and the timing of irreversible surgical interventions in 17β-HSD3 deficiency. We described three genetically confirmed cases of 46XY DSD due to 17β-HSD3 deficiency. All of them had female-appearing external genitalia, and the third case had well-developed breasts with clitoromegaly. The biochemical evaluation showed hCG-stimulated T/A ratios of 0.4 and 0.35 in Cases 1 and 2, respectively, and an unstimulated T/A ratio of 0.25 in Case 3. Molecular analysis revealed three different 17β-HSD3 deficiency remains a challenging 46 XY DSD due to its clinical heterogeneity and diverse molecular spectrum. This report adds to current molecular knowledge by reporting two novel variants in the Show less

It is well-known that the conversion of normal colon epithelium to adenoma and then to carcinoma stems from acquired molecular changes in the genome. The genetic basis of colorectal cancer has been elucidated to a certain extent, and much remains to be known about the identity of specific cancer genes that are associated with the advancement of colorectal cancer from one stage to the next. Here in this study we attempted to identify novel cancer genes that could underlie the stage-specific progression and metastasis of colorectal cancer. We conducted a stage-based meta-analysis of the voluminous tumor genome-sequencing data and mined using multiple approaches for novel genes driving the progression to stage-II, stage-III and stage-IV colorectal cancer. The consensus of these driver genes seeded the construction of stage-specific networks, which were then analyzed for the centrality of genes, clustering of subnetworks, and enrichment of gene-ontology processes. Our study identified three novel driver genes as hubs for stage-II progression: DYNC1H1, GRIN2A, GRM1. Four novel driver genes were identified as hubs for stage-III progression: IGF1R, CPS1, SPTA1, DSP. Three novel driver genes were identified as hubs for stage-IV progression: GSK3B, GGT1, EIF2B5. We also identified several non-driver genes that appeared to underscore the progression of colorectal cancer. Our study yielded potential diagnostic biomarkers for colorectal cancer as well as novel stage-specific drug targets for rational intervention. Our methodology is extendable to the analysis of other types of cancer to fill the gaps in our knowledge. Show less