Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.

Most eukaryotic cells have mitochondrial networks that can change in shape, distribution, and size depending on cellular metabolic demands and environments. Mitochondrial quality control is critical for various mitochondrial functions including energy production, redox homeostasis, intracellular calcium handling, cell differentiation, proliferation, and cell death. Quality control mechanisms within mitochondria consist of antioxidant defenses, protein quality control, DNA damage repair systems, mitochondrial fusion and fission, mitophagy, and mitochondrial biogenesis. Defects in mitochondrial quality control and disruption of mitochondrial homeostasis are common characteristics of various kidney cell types under hyperglycemic conditions. Such defects contribute to diabetes-induced pathologies in renal tubular cells, podocytes, endothelial cells, and immune cells. In this review, we focus on the roles of mitochondrial quality control in diabetic kidney disease pathogenesis and discuss current research evidence and future directions.

Prostate cancer remains a leading cause of cancer-related mortality and castration-resistant prostate cancer (CRPC) is a critical therapeutic challenge. This review establishes a conceptual framework analyzing ferroptosis vulnerability through two principles: “robustness through redundancy” in defense systems and the “evolutionary arms race” between androgen receptor (AR) signaling and oxidative resistance. We traced the evolutionary trajectory of hormone-sensitive diseases, where the AR coordinates ferroptosis defenses via SLC7A11, MBOAT2, and PEX10 regulation through progressive adaptations: AR-V7 splice variants that maintain defense independently of androgens, AR amplification conferring hypersensitivity, and AR-independent JMJD6-ATF4 bypass in SPOP-mutated tumors. This transforms ferroptosis from a static vulnerability to a stage-specific strategy. Novel approaches include menadione-based VPS34 targeting, which induces triaptosis through an oxidative endosomal catastrophe. We categorized the rational combinations mechanistically as vertical inhibition (multi-step targeting of single pathways), horizontal inhibition (synthetic lethality across parallel defenses), and vulnerability induction (creating exploitable dependencies). Ferroptosis-induced immunogenic cell death enables synergy with checkpoint inhibitors, potentially transforming immunologically “cold” prostate tumors. This review establishes ferroptosis targeting as a precision medicine paradigm exploiting the tension between the oxidative requirements of cancer cells and their evolved, yet architecturally vulnerable, defense systems, providing a framework for stage-specific, biomarker-guided interventions.

Emerging evidence suggests that the timing of eating and exercise over the course of the day is paramount to metabolism and physical function. This review highlights seminal studies showing that adipocyte AMPKα2 signaling controls circadian adipose tissue–skeletal muscle communication. Day-restricted feeding has been shown to improve exercise performance via adipocyte-specific activation of AMPKα2, which controls fat–muscle crosstalk in a time-of-day dependent manner. This review also discusses corroborating experimental studies designating mesenchymal stem cells as key cellular mediators, showing that exercise in the afternoon leads to better metabolic effects in humans, and illustrating how incorrect timing of food intake leads to leptin resistance and metabolic dysregulation. Multi-omics strategies have shed light on the molecular mechanisms underlying such effects of time, showing the circadian control of metabolic processes across tissues. These results advance our knowledge of chronometabolism and offer exciting temporal intervention treatments for metabolic diseases, such as time-restricted feeding, timed exercise, and chronopharmacological targeting of AMPK. Fat–muscle crosstalk, physical performance, and metabolic health outcomes can possibly be optimized by synchronizing dietary and exercise timing with endogenous circadian rhythms.

Background/Objectives: Fluid overload is an important risk factor for protein-energy wasting, which could lead to poor outcomes, such as higher morbidity and mortality, in patients with chronic kidney disease (CKD). This study aimed to validate the possible myokine as a biomarker of volume status in patients with non-dialysis CKD. Methods: In total, 151 patients with CKD were enrolled from a single medical center. Demographic data were collected via medical record review. Bioimpedance analysis was performed to measure body composition, and physical performance was assessed by measuring hand grip strength. Results: The physical performance of hand grip strength (21.9 ± 8.7 vs. 19.0 ± 10.1 kg, p = 0.233) and walking speed (1.05 ± 0.29 vs. 0.86 ± 0.52 m/s, p = 0.192) was higher in the low extracellular water/total body water (ECW/TBW) ratio group. Although higher, the median value of the brain-derived neurotrophic factor (BDNF) was not significant in the low ECW/TBW ratio group. Despite that, it had significant negative correlations with the ECW/TBW ratio in Pearson’s correlation analyses (r = −0.329, p < 0.001; r = −0.287, p < 0.001; and r = −0.238, p = 0.003). Linear regression analysis showed that the BDNF level had a significant negative relationship with the ECW/TBW ratio and significant associations even after multivariate analysis. Conclusions: Among myokines, BDNF had a significant negative relationship with the ECW/TBW ratio, suggesting that BDNF could be a possible biomarker for volume status in patients with non-dialysis CKD.

Jihyun Baek, Jung-Woo Seo, Hyeon Seok Hwang, So-Young Lee, Hye Yun Jeong, Yang Gyun Kim, Ju-Young Moon, Jin Sug Kim, Kyung-Hwan Jeong, Byung Ha Chung, Chan-Duck Kim, Jae Berm Park, Yu Ho Lee, Sang-Ho Lee. Clin Transplant Res -0001;0:. https://doi.org/10.4285/ctr.25.0016