👤 Sunil Raghav

The obesity pandemic continues to increase in prevalence in children and adolescents, with its increase outpacing the rate of adult obesity; the human developmental index, body mass index, and family income all display associations to childhood obesity. There are numerous adverse complications of childhood obesity, including cardiovascular, endocrine, and gastrointestinal manifestations. Obesity is thought to be an interaction of several different factors, such as leptin, proopiomelanocortin, glucose uptake in adipocytes, melanocortin receptor 4, protein convertase 1/3, brain-derived neurotrophic factor, fat-mass and obesity-associated gene, melanocortin receptor 4, tumor necrosis factor, interleukin-6, and long noncoding RNA. Epigenetic regulation, the unique gut microbiome role in contributing to obesity, environmental factors, and the social context of a child can precipitation of childhood obesity. In this review, we hope to explore the different medications for obesity, orlistat, glucagon-like peptide-1 agonists, liraglutide, semaglutide, exenatide, setmelanotide, metreleptin, naltrexone, lorcaserin, phentermine, metformin, fluoxetine, lisdexamfetamine, and zonisamide, while also reviewing surgeries such as the Roux-en-Y gastric bypass, laparoscopic or vertical sleeve gastrectomy, and adjustable gastric banding. Show less

India accounts for 26 % of global tuberculosis (TB) cases, with delayed diagnosis of Mycobacterium tuberculosis (MTB) and drug resistance exacerbating disease transmission. Conventional drug susceptibility testing (DST) remains time-consuming, while molecular tools like the Xpert MTB/RIF assay-though rapid-are limited to detecting MTB and rifampicin (RIF) resistance. Testing for isoniazid (INH) and second-line drugs requires the costly Xpert MTB/XDR assay. Although line probe assays (LPAs) identifies first- and second-line drug resistance, their accessibility is restricted to specialized laboratories. This underscores the need for a rapid, cost-effective alternative to diagnose resistance to INH and fluoroquinolones (FQs). A cross-sectional study was performed at the Department of Microbiology, AIIMS Bhubaneswar, and the Intermediate Reference Laboratory (IRL), Cuttack, from March 2022 to April 2023. MTB isolates (n = 123) were analyzed using LPAs (Hain Lifescience's Genotype MTBDRplus and Genotype MTBDRsl) and multiplex allele-specific (MAS) PCR. The MAS-PCR targeted mutations in katG codon 315 and the inhA-15 promoter region for INH resistance, and gyrA codon 94 for FQ resistance. MAS-PCR identified INH resistance in 28/123 (22.76 %) isolates. Compared to LPA, MAS-PCR demonstrated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 80.77 %, 93.81 %, 77.78 %, 94.79 %, and 91.06 %, respectively, for INH resistance. For FQ resistance, MAS-PCR identified 19/123 (15.44 %) resistant isolates, with sensitivity, specificity, PPV, NPV, and accuracy of 87.50 %, 95.33 %, 73.68 %, 98.08 %, and 94.31 %, respectively, relative to LPA. MAS-PCR offers a rapid, technically feasible, and cost-effective method for detecting resistance to INH and FQs. Its high accuracy and affordability position it as a viable alternative in resource-limited settings, facilitating timely TB diagnosis and resistance management. Show less

The interaction between stromal and tumor cells in tumor microenvironment is a crucial factor in Mantle cell lymphoma (MCL) progression and therapy resistance. We have identified a long non-coding RNA, CERS6-AS1, upregulated in MCL and associated with poor overall survival. CERS6-AS1 expression was elevated in primary MCL within stromal microenvironment and in a subset of MCL cells adhered to stromal layer. These stromal-adhered MCL-subsets exhibited cancer stem cell signatures than suspension counterparts. Mechanistically, we found that downregulating CERS6-AS1 in MCL reduced Fibroblast Growth Factor Receptor-1 (FGFR1), expression attributed to loss of its interaction with RNA-binding protein nucleolin. In addition, using in-silico approach, we have discovered a direct interaction between nucleolin and 5'UTR of FGFR1, thereby regulating FGFR1 transcript stability. We discovered a positive association of CERS6-AS1 with cancer stem cell signatures, and Wnt signaling. Building on these, we explored potential therapeutic strategies where combining nucleolin-targeting agent with FGFR1 inhibition significantly contributed to reversing cancer stem cell signatures and abrogated primary MCL cell growth on stromal layer. These findings provide mechanistic insights into regulatory network involving CERS6-AS1, nucleolin, and FGFR1 axis-associated crosstalk between tumor cells and stromal cell interaction and highlights therapeutic potential of targeting a non-coding RNA in MCL. Show less

Dendritic cells (DCs) undergo rapid metabolic reprogramming to generate signal-specific immune responses. The fine control of cellular metabolism underlying DC immune tolerance remains elusive. We have recently reported that NCoR1 ablation generates immune-tolerant DCs through enhanced IL-10, IL-27 and SOCS3 expression. In this study, we did comprehensive metabolic profiling of these tolerogenic DCs and identified that they meet their energy requirements through enhanced glycolysis and oxidative phosphorylation (OXPHOS), supported by fatty acid oxidation-driven oxygen consumption. In addition, the reduced pyruvate and glutamine oxidation with a broken TCA cycle maintains the tolerogenic state of the cells. Mechanistically, the AKT-mTOR-HIF-1α-axis mediated glycolysis and CPT1a-driven β-oxidation were enhanced in these tolerogenic DCs. To confirm these observations, we used synthetic metabolic inhibitors and found that the combined inhibition of HIF-1α and CPT1a using KC7F2 and etomoxir, respectively, compromised the overall transcriptional signature of immunological tolerance including the regulatory cytokines IL-10 and IL-27. Functionally, treatment of tolerogenic DCs with dual KC7F2 and etomoxir treatment perturbed the polarization of co-cultured naïve CD4 Show less