👤 Shital K Barman

Type II diabetes mellites (TIIDM) characterized by hyperglycemia, insulin resistance, insensitivity, and pancreatic β-cell atrophy has gained concern due to high rise in such cases globally. This study highlighted the therapeutic potency of a novel polyherbal formulation (PHF) of Phyllanthus urinaria and Adhatoda vasica Nees mice by in vitro, in vivo, and in silico analysis in high-fat diet (HFD)-streptozotocin (STZ)-induced Swiss albino. The findings showed significant inhibition of α-amylase and α-glucosidase activity of the PHF along with decreased blood glucose level, increased glycogen and serum insulin level, elevated mRNA expression of GIPR and GLP1R, GLUT2, GLUT4, INSR, INS1, INS2, TCF7L2, and Pdx1 in both low and high dose of PHF-treated mice as compared to HFD-STZ-induced diabetic mice. Western blot results also demonstrated augmented insulin protein level in both PHF-treated groups. Okanin and vomicine, identified from LCMS analysis as potent antidiabetic bioactive compounds bind to dipeptidyl peptidase 4 (DPP4) with a binding energy of -8.04 and -7.81 kcal/mol, respectively, as compared to standard drug metformin (-5.33 kcal/mol). Inhibition of DDP-4 by bioactives of PHF aids in enhanced secretion of incretion hormones leading to insulin secretion thereby established itself as a complementary and alternative therapeutics in the management of diet-induced TIIDM. Show less

A significant gap in the knowledge of zinc homeostasis exists for breast cancer cells. In this study, we investigated the transcriptomic response of the luminal breast cancer cells (MCF-7) to the exposure of extracellular zinc using next-generation RNA sequencing. The dataset was collected for three time points (T0, T30, and T120) in the time course of zinc treatment, which revealed the dramatic increase, up to 869-fold, of the gene expression for metallothioneins (MT1B, MT1F, MT1X, and MT2A) and the zinc exporter ZnT1 (SLC30A1) at T30, continuingly through to T120. The similar dynamic expression pattern was found for the autophagy-related gene (VMP1) and numerous genes for zinc finger proteins (e.g. RNF165, ZNF365, ZBTB2, SNAI1, ZNF442, ZNF547, ZNF563, and ZNF296). These findings point to the all-hands-on-deck strategy adopted by the cancer cells for maintaining zinc homeostasis. The stress responsive genes encoding heat shock proteins (HSPA1A, HSPA1B, HSPA1L, HSPA4L, HSPA6, HSPA8, HSPH1, HSP90AA1, and HSP90AB1) and the MTF-1 biomarker genes (AKR1C2, CLU, ATF3, GDF15, HMOX1, MAP1A, MAFG, SESN2, and UBC) were also differentially up-regulated at T120, suggesting a role of heat shock proteins and the MTF-1 related stress proteins in dealing with zinc exposure. It is for the first time that the gene encoding Polo-like kinase 2 (PLK2) was found to be involved in zinc-related response. The top differentially expressed genes were validated by qRT-PCR and further extended to the basal type breast cancer cells (MDA-MB-231). It was found that the expression level of SLC30A1 in MDA-MB-231 was higher than MCF-7 in response to zinc exposure. Taken together, the findings contribute to our knowledge and understanding of zinc homeostasis in breast cancer cells. Show less