👤 Ajita Shree

Pancreatic islets undergo coordinated cellular remodeling during obesity-induced insulin resistance (IR). However, the associated molecular changes across endocrine and non-endocrine compartments remain largely unexplored. Here, using longitudinal single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on islets from C57BL/6 mice subjected to high-fat diet (HFD) feeding for 8, 16, and 24 weeks, along with age-matched controls on regular chow, we mapped dynamic changes in islet cell composition and transcriptional states. Beta cells demonstrated pronounced stress-induced reprogramming, with the emergence of proliferative and dysfunctional subsets. Alpha and delta cell fractions declined under HFD, despite increased polyhormonal biosynthesis, suggesting functional rather than numerical adaptation. Immune profiling showed robust expansion of proinflammatory M1 macrophages and upregulation of NF-κB and chemotaxis pathways, particularly at 16 weeks. Notably, cell-cell communication analyses revealed diet-specific disruption in signaling networks. Under HFD conditions, intercellular communication among beta cells, macrophages, and delta cells was markedly altered, leading to the disruption of key signaling pathways such as the gastric inhibitory polypeptide receptor (GIPR) and major histocompatibility complex-I (MHC-I). Notably, C-C motif chemokine ligand 27A ( Show less

HNSCC is a highly aggressive cancer of the head and neck region, and there is an urgent need to find novel potential targets for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) have emerged as important therapeutic and diagnostic targets for multiple cancers, including HNSCC. LINC01518 promotes the proliferation of oesophageal cancer cells, but the involvement of LINC01518 in HNSCC pathophysiology is unknown. We show that LINC01518 expression is significantly upregulated in high-grade HNSCC tumor samples in comparison to normal tissue, and transforming growth factor- β (TGF-β) promotes LINC01518 expression in HNSCC cell lines. Loss-of-function studies suggest that LINC01518 promotes cell proliferation, migration, and invasion in HNSCC cells. In addition, LINC01518 depletion sensitizes HNSCC cells to cisplatin-mediated apoptosis. Mechanistically, LINC01518 acts as a competitive endogenous RNA and binds to miR-1-3p and miR-216b-5p, resulting in up-regulation of their target genes Slug and GRP78, respectively. Our findings suggest that LINC01518 is an attractive therapeutic target for HNSCC. Show less

Incretin therapy is one of the most potential approaches in the treatment of diabetes. In contrast to markedly available drugs, the herbal incretin modulators have lesser side effects with low economic cost. The main aim of this work was to analyze the potential of previously reported DPPIV inhibitor, aqueous extract of Pueraria tuberosa tubers (PTY-2) as incretin hormones receptor agonist against streptozotocin (STZ)-induced diabetes. Chronic diabetes was induced with STZ (65mg/kg bw) in rats for 60days and grouped into diabetic control and PTY-2. Expression of genes was assessed by PCR, IHC, and ELISA. Morphological analysis of tissue was observed using H & E stain. In silico molecular docking approach has been used to see the interaction of active phytochemicals of PTY-2 on the basis of their binding energy [kcal/mol] and dissociation constant [pM] using YASARA software. Interactive visualization was done using Discovery studio 3.0. In comparison to diabetic control, the size and number of islet cells along with the plasma level of GLP-1, GIP, and pancreatic expressions of GLP-1R, GIP-R, Bcl2, and insulin were enhanced significantly after PTY-2 treatment. Through in silico molecular docking, tuberostan showed the best interaction for GLP-1R with binding energy at 8.15kcal/mol and dissociation constant at 1061624.125 pM. Puererone showed the best interaction for GIP-R with binding energy at 8.31kcal/mol and dissociation constant at 810381 pM. In addition to previously studied DPPIV inhibitor, PTY-2 also acts as incretin receptors agonist and protects against STZ-induced diabetes by down regulating β cells apoptosis. Show less