Association between bladder cancer treatment and female sexual function.

INTRODUCTION: Bladder cancer ranks 17th in prevalence of cancer types among women, and the trend is rising. The increased risk of female sexual dysfunction (FSD) after radical cystectomy (RC) underscores the need for greater focus on preserving and mitigating FSD. OBJECTIVES: To place greater emphasis on the importance of female sexual function (FSF) in the treatment of bladder cancer and stimulate additional research to discover more effective solutions for enhancing the overall quality of life. METHODS: This review used a narrative approach. Previous reviews on FSF after RC have provided limited and 1-sided solutions due to the lack of research. What makes this review unique is its innovative approach: it includes all available measures curing FSD as well as comparative analyses based on experimental data, thus making the findings more comprehensive. A detailed perspective of treatments for female bladder cancer is provided, including nerve- and organ-sparing RC, robot-assisted RC, and radiotherapy. We also analyze the impact of treatments for female bladder cancer on postoperative FSD. Additionally, solutions for addressing or alleviating postoperative FSD are summarized, such as urinary diversion, vaginal reconstruction, and drug and nondrug treatment. RESULTS: Research has suggested that robot-assisted nerve- and organ-sparing RC is promising. Moreover, orthotopic neobladder among urinary diversions without a stoma helps to maintain a positive female body image. If part of the anterior vaginal wall must be removed during RC, vaginal reconstruction can restore the dimensions with synthetic grafts and biologic scaffolds. Additionally, postoperative measures, such as vaginal laser and hormone therapy, and use of vaginal dilators and lubricants have a significant role in reducing distress caused by FSD to provide maximum relief. CONCLUSIONS: To support FSF after RC, various interventions are needed, and urologists must focus on patient recovery while minimizing treatment impact on FSF as much as possible.

Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression. Further metabolic flux analysis revealed that Tkt deletion increased hepatic inosine levels to activate the protein kinase A-cAMP response element binding protein cascade, promote phosphatidylcholine synthesis, and improve mitochondrial function. Moreover, insulin induced hepatic TKT to limit inosine-dependent mitochondrial activity. Importantly, N-acetylgalactosamine (GalNAc)-siRNA conjugates targeting hepatic TKT showed promising therapeutic effects on mouse MAFLD. Our study uncovers how hyperinsulinemia regulates TKT-orchestrated inosine metabolism and mitochondrial function and provides a novel therapeutic strategy for MAFLD prevention and treatment.