High mobility group box 1 (HMGB1), which plays a crucial role in cancer progression, remains incompletely elucidated due to the high heterogeneity and complex tumor microenvironment of prostate cancer (PCa). This study, through single-cell transcriptomic analysis, provided a comprehensive elucidation of cellular heterogeneity in PCa tissues and revealed the essential role of HMGB1 in the progression of PCa by using in vitro cell experiments. Single-cell analysis revealed that an epithelial subpopulation with high levels of HMGB1 (HMGB1+ Malignant LE) significantly increased in PCa tissues, which was closely correlated with the malignant characteristics of the tumor. KEGG enrichment analysis revealed that pathways associated with autophagy, mitophagy, and apoptosis were significantly enriched in the HMGB1+ Malignant LE sub-group. In vitro cell experiments further confirmed that knocking down HMGB1 significantly inhibited the proliferation, migration, and invasive capacity of PCa cells, while inducing cellular apoptosis and cell cycle arrest. These findings suggest that HMGB1 promotes PCa malignancy by modulating tumor cell metabolism and cellular cycle progression. This study provides novel insights into the role of HMGB1 in PCa and lays theoretical groundwork for the development of therapeutic strategies targeting HMGB1.

Metastatic prostate cancer is highly heterogeneous, posing challenges for the precise use of platinum-based chemotherapy. This narrative review proposes a dual "genotype-phenotype" stratification framework to support structured clinical decision-making. On the genotype arm, we review the "response gradient" within homologous recombination repair (HRR) gene aberrations, with strong evidence that BRCA2 mutations (especially biallelic loss) are the most robust predictors of platinum sensitivity, whereas the benefit in other genes (e.g., ATM, CDK12) is uncertain. On the phenotype arm, we focus on aggressive-variant/neuroendocrine prostate cancer (AVPC/NEPC), showing that platinum-containing regimens can induce high initial response rates but require optimization to prolong response duration. In addition, we critically synthesize evidence on sequential and combination strategies of platinum with poly(ADP-ribose) polymerase (PARP) inhibitors and taxanes, and discuss toxicity management in older and comorbid patients. Future progress will likely require integration of functional HRD assays, dynamic liquid-biopsy monitoring, and individualized supportive care to determine how short-term platinum responses can be translated into more durable clinical benefit.

The kidney is a high-energy-consuming organ, and glucose is one of its principal fuel sources. It has been documented that disturbed renal glucose metabolism occurs in acute kidney injury (AKI), but whether these disturbances are consistent in different types of AKI, and how they change during the transition from AKI to chronic kidney disease (CKD), remain to be addressed. In this study, we used AKI models induced by cisplatin (20 mg/kg, 48 h), lipopolysaccharide (10 mg/kg, 48 h), and ischemia-reperfusion (48 h) to mimic distinct etiologies, and the catalytic enzymes involved in glucose transport, gluconeogenesis, and glycolysis were evaluated at both mRNA and protein levels by qPCR and immunofluorescence, respectively. In AKI, sodium-glucose cotransporter 2 (SGLT2) and fructose-1,6-bisphosphatase 1 (FBP1) protein levels were decreased, whereas the glycolytic enzymes hexokinase 2 (HK2), phosphofructokinase muscle type (PFKM), and pyruvate kinase M2 (PKM2) protein levels were increased. During the AKI-to-CKD transition, SGLT2 remained low; HK2, PFKM, PKM2, and FBP1 displayed a biphasic pattern (early rise, late fall) that varied with injury dose and time. These findings describe the expression changes of glucose metabolic enzymes during AKI and the AKI-to-CKD transition. Direct measurements of glycolytic activity were not performed; therefore, the relationship between these expression changes and actual metabolic function remains to be determined. This study provides a descriptive foundation for future investigations of glucose metabolism during the AKI-to-CKD transition.