Epigenetic silencing of tumor suppressor genes (TSGs) is a key driver of colorectal cancer (CRC) progression, with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) frequently inactivated through promoter hypermethylation. This study explored the association between DNA methyltransferase 1 (DNMT1) suppression, PTEN reactivation, and miR-29a-3p modulation following 5-aza-2'-deoxycytidine (5-aza-dC) treatment in CRC cell models. Bioinformatic analyses revealed DNMT1 overexpression, increased PTEN promoter methylation, and a potential regulatory network associated with miR-29a-3p. In vitro, HCT116 and SW620 cells treated with 5-aza-dC exhibited dose-dependent reductions in cell viability, with IC₅₀ values of 12.38 ± 0.98 μM and 10.04 ± 0.98 μM, respectively. Treatment with 5-aza-dC induced significant PTEN re-expression and DNMT1 downregulation at both the mRNA and protein levels. Methylation-specific PCR (MSP-PCR) suggested reduced PTEN promoter methylation following treatment. Additionally, miR-29a-3p expression was significantly upregulated. These findings suggest that 5-aza-dC restores PTEN expression in association with DNMT1 suppression and PTEN promoter demethylation, while miR-29a-3p upregulation may reflect an associated epigenetic response requiring further mechanistic validation.

Type 2 diabetes mellites (T2DM) often leads to renal dysfunction, necessitating novel therapeutic interventions. This study aimed to evaluate the influence of zinc oxide nanoparticles (ZnO NPs) and Trigonella foenum- graecum (TFG) extract on glucose level, kidney function, lipid profile, and antioxidants in diabetic-induced rats, with a focus on its potential therapeutic role in mitigating diabetes-related complications accompanied with histological examination of kidney tissues in rat models of T2DM. Forty adult Wister albino rats were divided into five groups as follows: Group I (non-diabetic control group); Group II (diabetic control group); Group III (diabetic rats treated with ZnO NPs); Group IV (diabetic rats treated with TFG); Group V (diabetic rats treated with the combination of TFG and ZnO NPs). Biochemical parameters such as Glucose (GLU), Uric acid (UA), Blood urea nitrogen (BUN), Creatinine (CR), Triglyceride (TG), Cholesterol (CHOL), High-density lipoprotein-cholesterol (HDL-c), Low-density lipoprotein-cholesterol (LDL-c), Glutathione (GSH), Superoxide dismutase (SOD), Malondialdehyde (MDA) and Catalase (CAT) along with histological investigation for renal tissue. Treatment with TFG, ZnO NPs, and their combination exhibited a significant decrease in serum glucose (GLU) level, revised lipid profile to normalcy, reduced oxidative stress, and enhanced the histological pattern for kidney tissue, highlighting their therapeutic potential. These findings suggest that ZnO NPs and TFG extract significantly improve glucose metabolism, lipid profile, renal function, and oxidative stress in T2DM

Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia, dyslipidemia, nephropathy, and oxidative stress, highlighting the need for innovative therapeutic strategies. This study investigated the potential of green-synthesized silver nanoparticles (Ag NPs), prepared using Moringa oleifera (M. oleifera) leaf extract, to mitigate diabetes-related complications in a streptozotocin (STZ)-induced diabetic rat model. Silver nanoparticles were synthesized via a green method and characterized using transmission electron microscopy (TEM). Fifty adult albino rats were divided into five groups: Group I (control), Group II (diabetic), Group III (diabetic treated with Ag NPs), Group IV (diabetic treated with M. oleifera), and Group V (diabetic receiving combination therapy). Biochemical parameters related to renal function, lipid profile, and antioxidant biomarkers were measured, along with a histological examination of kidney tissue. Combination treatment exhibited superior therapeutic efficacy, significantly reducing fasting blood glucose, HbA1c, total cholesterol, triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) while increasing high-density lipoprotein cholesterol (HDL-c). Additionally, antioxidant biomarkers improved, with elevated levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), alongside a reduction in malondialdehyde (MDA). These effects were accompanied by significant histological improvements in kidney architecture, indicating nephroprotective properties. Transmission electron microscopy confirmed the formation of uniform, spherical Ag NPs, while combination treatment demonstrated synergistic effects, suggesting that M. oleifera enhances nanoparticle efficacy through its antioxidant properties. This study underscores the therapeutic potential of green-synthesized Ag NPs and M. oleifera leaf extract as a promising approach for managing DM and its complications.

Background/Objectives: Loss of phosphatase and tensin homolog (PTEN) activity is a frequent feature of non-small-cell lung cancer (NSCLC), and epigenetic repression may contribute to its reduced expression. This study investigated the effects of 5-aza-2′-deoxycytidine (5-aza-dC) on PTEN, DNA methyltransferase 1 (DNMT1), PTEN promoter methylation-specific amplification patterns, and miR-148a-3p expression in NSCLC models. Methods: Publicly available cancer-genomics datasets were analyzed to compare PTEN and DNMT1 transcript abundance and to assess the association between PTEN methylation and transcript abundance in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). A549 and H460 cells were exposed to 2.5 or 5 µM 5-aza-dC for 72 h. Reverse-transcription quantitative PCR (RT-qPCR), Western blotting, methylation-specific PCR (MSP-PCR), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate RNA expression, protein abundance, methylation-specific amplification, and metabolic activity, respectively. Results: Bioinformatic analyses showed lower PTEN and higher DNMT1 expression in both NSCLC subtypes, together with inverse associations between PTEN methylation and transcript abundance. In both cell lines, 5-aza-dC reduced MTT metabolic activity and DNMT1 expression. PTEN mRNA and protein abundance increased significantly at 5 µM, whereas no significant changes were detected at 2.5 µM. MSP-PCR revealed persistent heterogeneous PTEN methylation-specific amplification patterns without clear evidence of progressive promoter demethylation. miR-148a-3p exhibited a biphasic response in A549 cells but remained unchanged in H460 cells. Conclusions: These findings support an association between 5-aza-dC exposure, increased PTEN expression, and reduced DNMT1 expression in NSCLC cells. Quantitative methylation analysis and mechanistic validation are required to clarify the contribution of miR-148a-3p to this regulatory association.

Colorectal cancer (CRC) is a severe neoplasm that is associated with high mortality rates. Aberrant epigenetic alterations are associated with several stages of tumor growth. The FDA has approved 5-Azacytidine (5-aza) for the treatment of specific types of cancers, including leukemia and MDS. Previous studies have demonstrated that E-cadherin1 (CDH1) expression is suppressed in CRC. However, the regulatory mechanisms underlying CDH1 suppression remain unclear. This investigation focused on examining whether 5-aza has a significant effect on CRC treatment using the human LS513 cell line. MTT test was used to evaluate the LS513 cell viability following 5-aza treatment; cell proliferation along with autophagy were assessed using flow cytometry; CDH1 expression was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, while methylation-specific PCR (MSP-PCR) was used to investigate the degree of methylation in the CDH1 promoter region. These Findings indicate that 5-aza reduced the viability of LS513 cells in a concentration-dependent manner (P < 0.05). 5-aza treatment arrested the cell cycle at the G2/M phase, triggered autophagy, and upregulated CDH1 expression following deactivation of the hypermethylated CDH1 promoter.