Prostate cancer (PCa) is one of the most common malignant tumors, and most patients develop castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). Metabolic plasticity, which allows cancer cells to reprogram glucose, lipid, and glutamine utilization, plays a key role. This metabolic adaptation meets the bioenergetic and biosynthetic needs of tumor cells, and it can interact with the androgen receptor (AR) signaling pathway bidirectionally to evade immune surveillance via metabolic reprogramming. Current treatments include single metabolic node inhibition and AR-guided combination therapy. However, due to intratumoral metabolic heterogeneity, compensatory pathway activation, and systemic metabolic toxicity of drugs, there is a need to explore new intervention targets and strategies. This article comprehensively discusses the metabolic network, regulatory mechanism, and current challenges of CRPC in order to provide a theoretical basis for clinical prevention and treatment.
Yanzhi Lou, Zhengda Lou, Luo He et al.· Cellular Signalling· 0 citations
Sepsis-associated acute kidney injury (SA-AKI) is a distinct form of acute kidney injury in critically ill patients. It is characterized by tubular epithelial cell damage and apoptosis. The Hippo-Yes-associated protein (YAP) pathway plays dual roles in renal injury and repair, with YAP serving as a key downstream effector; however, its function during the early stages of SA-AKI remains unclear. In this study, we utilized two mouse models (lipopolysaccharide-induced and cecal ligation and perforation) and human proximal tubule epithelial cells (HK-2 cells) to investigate YAP’s roles in SA-AKI. YAP expression was manipulated by adeno-associated virus 9 (AAV9)-mediated overexpression and pharmacological inhibition with verteporfin. Renal injury markers, inflammatory cytokines, and related pathway proteins were evaluated. Histopathological analyses, including HE and PAS staining, revealed increased tubular cell apoptosis and tissue disruption. In both SA-AKI models, YAP expression and nuclear localization were significantly increased at 24 h after injury induction. YAP overexpression exacerbated renal injury and inflammatory responses, whereas pharmacological inhibition of YAP markedly attenuated kidney damage. Mechanistically, YAP-mediated renal injury was associated with dysregulation of the PI3K-AKT signaling pathway. In summary, these findings indicate that YAP may be involved in renal pathological damage in early SA-AKI and highlight its potential role in disease progression.
Luo He, Yangyang Li, Jingkai Wang et al.· Bratislava Medical Journal· 0 citations
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