Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma.

This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease's epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients.

Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model.

Introduction: Angiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension. Methods: Dahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696. Results and discussion: The study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.

Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses.

Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8+ T and CD49b+ NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3+ Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.