Quercetin (QUE) belonging to the flavonoid class is a common phytochemical present in the daily diet of some individuals. Quercetin is an important source of free radical scavengers. This property makes this flavonoid a reliable antioxidant with the following properties: anti-inflammatory, anti-diabetic, antimicrobial and anti-carcinogenic. Sodium butyrate (NaBu) acts as a histone deacetylase inhibitor (HDACi) and is known to regulate apoptosis in cancer cells. Combining natural flavonoids such as QUE with different substances may synergistically enhance their anti-carcinogenic capacity. Thus, the aim of this study was to examine the combined treatment effects of QUE and NaBu in hormone-sensitive breast cancer cells in vitro. MCF-7 breast cancer cells were treated with QUE alone, NaBu alone, as well as QUE and NaBu combined to determine the following: cell proliferation, levels of protein annexin A5 (ANXA5) and reactive oxygen species (ROS), mRNA protein expression, as well as cell and nuclear morphology. Data demonstrated that either QUE or NaBu alone inhibited cell proliferation, and reduced levels protein ANXA5, ROS and mRNA protein expression, The combination of QUE and NaBu produced a significant synergistic inhibitory effect compared to treatment groups of QUE or NaBu alone. In conclusion, our findings showed that the combination treatment of QUE and NaBu may constitute a promising therapeutic approach to breast cancer treatment but this needs further molecular and in vivo investigations.

Obesity is a growing global health concern that leads to metabolic imbalances and progressive cardiac remodelling. This study investigated whether semaglutide (SMG) can counteract the disruption to the gut-heart-metabolic axis and associated myocardial injury caused by obesity. Twenty-one male Wistar rats were assigned to control, obese (OB), and obese+semaglutide (OB + SMG) groups. The control group was fed a normal diet, while the obese groups were given a cafeteria diet for 16 weeks. In addition, the OB + SMG group received 150 mcg/kg of SMG subcutaneously once a week for the last four weeks. The following were measured alongside HOMA indices: Lipid profile, cardiac enzymes, leptin, insulin, TMAO and LPS levels. Myocardial and intestinal samples were assessed biochemically and histopathological for the levels of MMP-2/MMP-9, TIMP-1, TGF-β, IL-1β, HO-1, occludin, ZO-1 and claudin. Obesity markedly increased body weight, fasting glucose, leptin, insulin resistance, the atherogenic index and cardiac risk, while also increasing LPS, TMAO, TGF-β, IL-1β, MMP-2/MMP-9 activity and decreasing TIMP-1. Semaglutide significantly reversed these abnormalities, improving metabolic indices, restoring the balance between MMPs and TIMPs, and reducing inflammatory mediators. Histological analysis revealed reduced cardiomyocyte degeneration and enhanced intestinal epithelial architecture in the OB + SMG group. Semaglutide notably enhanced the expression of occludin, claudin, and ZO-1, supporting strengthened intestinal barrier integrity, and restored HO-1 expression, indicating improved antioxidant defenses. These findings suggest that semaglutide provides cardioprotection in obesity by restoring gut barrier function, reducing inflammation and normalizing extracellular matrix turnover. By stabilizing the gut-heart-metabolic axis and mitigating structural myocardial injury, semaglutide may interrupt the progression from metabolic dysfunction to cardiomyopathy. This highlights its therapeutic potential in the treatment of obesity-related cardiovascular disease, extending beyond glycemic control.

Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation and ulcers in the lining of the colon and rectum. Spexin is a novel peptide with antioxidant and anti‐inflammatory properties. This study aims to elucidate the therapeutic effects and underlying mechanisms of spexin in mitigating acetic acid‐induced colitis in rats. Male Sprague Dawley rats were assigned to control (n = 14) and colitis (n = 21) groups. Colitis was induced via 5% acetic acid (AA) administration (1 mL, intrarect). Post‐induction, rats received subcutaneous saline (1 mL/kg), spexin (50 µg/kg/day), or oral sulfasalazine (500 mg/kg) for 5 days. Control groups received saline or spexin. After 24 h of the final treatment, colons were evaluated macroscopically, and levels of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐18 were determined by ELISA, oxidative stress markers myeloperoxidase (MPO), malondialdehyde (MDA) and glutathione (GSH) levels were measured spectrophotometrically and NOD‐like receptor pyrin domain‐containing 3 (NLRP3), nuclear factor‐κB (NF‐κB), caspase‐1 proteins were analyzed with Western Blot alongside histopathological assessments. Colitis induction significantly elevated macroscopic damage scores, stool consistency, inflammatory cytokines, MDA, MPO, and NLRP3, NF‐κB, caspase‐1, while reducing GSH levels (p < 0.001–0.01). Microscopic evaluations confirmed increased necrosis, submucosal edema, and inflammatory cell infiltration (p < 0.001). Spexin reversed these effects by enhancing GSH levels (p < 0.01), reducing macroscopic/microscopic scores, cytokines, MDA, and MPO levels (p < 0.05–0.001), and suppressing NLRP3, NF‐κB, and caspase‐1 activation (p < 0.01–0.001). For the first time that spexin ameluates acetic acid‐induced colitis in rats by modulating the NF‐κB/NLRP3 signaling pathway, reducing oxidative damage, enhancing antioxidant capacity, and suppressing inflammation.

Prostate cancer is a major planetary health challenge wherein new ways of thinking drug discovery and therapeutics innovation are much needed. Numerous studies have shown that autophagy inhibition holds a significant role as an adjunctive intervention in prostate cancer. Hydroxychloroquine (HCQ) has gained considerable attention due to its established role as an autophagy inhibitor across diverse cancer types, but its proteomics landscape and systems biology in prostate cancer are currently lacking in the literature. This study reports the proteomic responses to HCQ in prostate cancer cells, namely, androgen-dependent LNCaP and androgen-independent PC3 cells. Differentially expressed proteins and proteome in HCQ-treated cells were determined by label-free quantification with nano-high-performance liquid chromatography and tandem mass spectrometry (nHPLC-MS/MS), and harnessing bioinformatics tools. In PC3 cells, there was a marked shift toward metabolic reprogramming, highlighted by an upregulation of mitochondrial proteins in oxidative phosphorylation and tricarboxylic acid cycle, suggesting an adaptive mechanism to maintain energy production under therapeutic stress. In contrast, LNCaP cells prioritized proteostasis and cell cycle regulation, indicating a more conservative adaptation strategy. To the best of our knowledge, this study is the first to demonstrate the differential responses of prostate cancer cells to autophagy inhibition by HCQ, suggesting that a combination therapy approach, targeting distinct pathways in androgen-independent and androgen-dependent cells, could represent a promising treatment strategy. Moreover, the varied proteomic responses observed between these cell lines underscore the importance of personalized medicine in cancer therapy. Future translational and clinical research on HCQ and prostate cancer are called for.