This study employed green chemistry to synthesize copper nanoparticles (CuNPs) using fresh root extract of Withania somnifera. The size, shape, morphology, and stability of resultant CuNPs were investigated by UV‐Vis spectroscopy, FTIR, transmission electron microscopy (TEM), and energy‐dispersive spectrophotometer. Crude extracts were assessed phytochemically to determine the presence of alkaloids, flavonoids, phenols, saponins, steroids, and tannins. The UV‐Vis absorption spectra show maximum absorption at 330 nm, and FTIR showed the presence of biological molecules responsible for reducing Cu⁺ ions. In TEM and EDS analyses, the average diameter of the synthesized NPs was found to be 6.28 ± 1.13 nm. The crystal structure of synthesized nanoparticle was determined using XRD analysis and showed its peak at 36.34°, 43.33°, 50.47°, and 73.57°, which corresponds to the cubic lattice of copper. The synthesized nanoparticles (NPs) were tested for their in vitro antimicrobial activity against bacterial strains E. coli and S. aureus by the agar well diffusion method which showed higher efficiency against S. aureus. The antioxidant activity of the synthesized NPs was evaluated by DPPH assay, and the percentage of inhibition was found to be 62% at the concentration of 400 μg/ml and the IC50 value was 51.53 μg/ml. The present investigation suggests that the biosynthesized CuNPs showed prominent antibacterial and free radical scavenging potential. The result proved that root extract of W. somnifera could be applied for synthesis of nanoparticle CuNPs with high uniform particle size along with potent biological activity.

The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor crucial in regulating cellular homeostasis and apoptosis. The NRF2 gene has been implicated in various biological activities, including antioxidant, anti-inflammatory, and anticancer properties. NRF2 can be regulated genetically and epigenetically at the transcriptional, post-transcriptional, and translational levels. Although DNA methylation is one of the critical biological processes vital for gene expression, sometimes, anomalous methylation patterns result in the dysregulation of genes and consequent diseases and disorders. Several studies have reported promoter hypermethylation downregulated NRF2 expression and its downstream targets. In contrast to the unalterable nature of genetic patterns, epigenetic changes can be reversed, opening up new possibilities in developing therapies for various metabolic disorders and diseases. This review discusses the current state of the NRF2-mediated antioxidative and chemopreventive activities of several natural phytochemicals, including sulforaphane, resveratrol, curcumin, luteolin, corosolic acid, apigenin, and most other compounds that have been found to activate NRF2. This epigenetic reversal of hypermethylated NRF2 states provides new opportunities for research into dietary phytochemistry that affects the human epigenome and the possibility for cutting-edge approaches to target NRF2-mediated signaling to prevent chronic disorders.

The epigenetic regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal redox transcription factor, plays a crucial role in maintaining cellular homeostasis. Recent research has underscored the significance of epigenetic modifications of Nrf2 in the pathogenesis of diabetic foot ulcers (DFUs). This study investigates the epigenetic reversal of Nrf2 by pterostilbene (PTS) in human endothelial cells in a hyperglycemic microenvironment (HGM). The activation potential of PTS on Nrf2 was evaluated through ARE-Luciferase reporter assays and nuclear translocation studies. Following 72 h of exposure to an HGM, mRNA expression and protein levels of Nrf2 and its downstream targets NAD(P)H quinone oxidoreductase 1 (NQO1), heme-oxygenase 1(HO-1), superoxide dismutase (SOD), and catalase (CAT) exhibited a decrease, which was mitigated in PTS-pretreated endothelial cells. Epigenetic markers, including histone deacetylases (HDACs class I–IV) and DNA methyltransferases (DNMTs 1/3A and 3B), were found to be downregulated under diabetic conditions. Specifically, Nrf2-associated HDACs, including HDAC1, HDAC2, HDAC3, and HDAC4, were upregulated in HGM-induced endothelial cells. This upregulation was reversed in PTS-pretreated cells, except for HDAC2, which exhibited elevated expression in endothelial cells treated with PTS in a hyperglycemic microenvironment. Additionally, PTS was observed to reverse the activity of the methyltransferase enzyme DNMT. Furthermore, CpG islands in the Nrf2 promoter were hypermethylated in cells exposed to an HGM, a phenomenon potentially counteracted by PTS pretreatment, as shown by methyl-sensitive restriction enzyme PCR (MSRE-qPCR) analysis. Collectively, our findings highlight the ability of PTS to epigenetically regulate Nrf2 expression under hyperglycemic conditions, suggesting its therapeutic potential in managing diabetic complications.

Diabetes and Cancer are the most complex chronic diseases, accounting for significant global mortality and morbidity. The association between Type 2 DM (T2DM) and endometrial cancer (EC) is multifaced, sharing numerous risk factors, including insulin resistance, obesity, hypoxia, and oxidative stress. Hypoxia plays a vital role in T2DM pathogenesis by altering the insulin level and pancreatic β-cell failure through an imbalance between antioxidant enzymes and cellular oxidative levels, while chronic inflammation contributes to EC malignancy. HIF-1α is a potent transcription factor involved in modulating cellular responses to hypoxia within the disease environment. Targeting the HIF-1α signaling cascade, a major metabolic regulator may contribute to advanced therapeutic advances. This review focuses on the association between T2DM and EC, especially focusing on hypoxia and HIF signaling pathways. These intersect with key pathways involved in T2DM and EC pathology, such as insulin signaling, PI3K/AKT, mTOR pathway, MUC1/HIF-1α pathway, and hormonal imbalance. Understanding this complex relationship paves the way for future researchers to develop HIF-1α-targeted therapies that could lead to novel combination therapies to treat these comorbid conditions.

Diabetes mellitus (DM), particularly Type 2 DM (T2DM), is increasingly recognized as both a risk factor and an early manifestation of pancreatic ductal adenocarcinoma (PDAC), yet the molecular mechanisms bridging these conditions remain poorly understood. There is growing evidence that chronic metabolic stress in diabetes induces persistent cellular reprogramming and metabolic memory through stable post-translational and epigenetic alterations, independent of conventional insulin resistance, obesity, and inflammatory pathways. We aim to elucidate how hyperglycaemia and metabolic overload contribute to the accumulation of major intermediates, such as acetyl-CoA, Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), and reactive oxygen species, which induce broad changes in post-translational modifications in diabetes-induced PDAC. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Web of Science databases, to retrieve studies published between 2005 and 2025. This review synthesizes current understanding of post-translational modifications (PTM) dynamics in diabetes-associated PDAC, with emphasis on their role in modulating oncogenic pathways such as KRAS-MAPK and PI3K-AKT. We introduce the concept of PTM remodeling, wherein transient metabolic perturbations become persistently stabilized, contributing to metabolic memory and tumor initiation. In addition, we examine how PTM-driven alterations influence the pancreatic tumor microenvironment, including stromal activation, immune evasion, and metabolic crosstalk, reinforcing a bidirectional link between tumor progression and systemic metabolic dysfunction. Furthermore, emerging therapeutic strategies targeting PTM-regulating enzymes, metabolic substrates, and signaling nodes are discussed as potential approaches to disrupt this axis. Collectively, precision targeting of PTM-mediated metabolic reprogramming represents a promising framework for early intervention and therapeutic development in PDAC associated with diabetes.