Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.

In this current research, we conceptualized a novel nanotechnology-enabled synthesis approach of targeting HIV-harboring tissues via second-generation (G2) polyamidoamine (PAMAM) mannosylated (MPG2) dendrimers for programmed delivery of anti-HIV drugs efavirenz (EFV) and ritonavir (RTV). Briefly, here mannose served purpose of ligand in this EFV and RTV-loaded PAMAM G2 dendrimers, synthesized by divergent techniques, denoted as MPG2ER. The developed nanocarriers were characterized by different analytical tools FTIR, NMR, zeta potential, particle size, and surface morphology. The results of confocal microscopy showed substantial alterations in the morphology of H9 cells, favored by relatively higher drug uptake through the MPG2ER. Interestingly, the drug uptake study and cytotoxicity assay of MPG2ER demonstrated that it showed no significant toxicity up to 12.5 µM. A typical flow cytometry histogram also revealed that MPG2ER efficiently internalized both drugs, with an increase in drug uptake of up to 81.2 %. It also enhanced the plasma pharmacokinetics of EFV, with C_max7.68 μg/ml, AUC of 149.19 (μg/ml) * hr, and MRT of 26.87 hrs. Subsequently, tissue pharmacokinetics further evidence that MPG2ER accumulated more in distant Human immunodeficiency virus (HIV) reservoir tissues, such as the lymph nodes and spleen, but without exhibiting significant toxicity. Abovementioned compelling evidences strongly favored translational roles of MPG2 as a potential therapeutic strategy in the clinical eradication of HIV from viral reservoir tissue.

Diabetic foot ulcer (DFU) is one of the most common serious complications of diabetes mellitus and often results in amputation. This complication affects 15% of individuals with diabetes over their lifetime. This review investigates the role of epigenetic modifications in DFUs, as many epigenetic mechanisms contribute to the underlying pathogenesis of diabetes and its complications, including DFUs. Therefore, initiatives aimed at understanding these epigenetic mechanisms may represent a paradigm shift in diagnosing and treating DFUs. Molecular-level studies have been conducted to identify the clinical manifestations of epigenetics in diabetes and its associated complications, such as DFU. This review synthesizes recent literature on epigenetic mechanisms contributing to diabetic foot ulcer (DFU) pathogenesis and explores the therapeutic potential of natural compounds targeting these mechanisms. Through a structured search of databases including PubMed and Scopus, we identified key natural agents, such as curcumin and resveratrol, that modulate DNA methylation, histone modifications, and non-coding RNAs. Natural compounds, which are bioactive ingredients derived from natural organisms, may serve as lead molecules and promising drug candidates, offering an excellent alternative to synthetic drugs for managing and alleviating DFUs and related complications. These natural compounds exhibit pleiotropic activities, including anti-inflammatory and antimicrobial effects, stimulation of angiogenesis, antioxidant activity, facilitation of fibroblast migration, as well as the promotion of cytokines and growth factors; therefore, they hold significant potential as valuable adjuncts to conventional therapy.