Xueqin Chen

Type-2 diabetes mellitus (T2DM) is a complex metabolic disorder that adversely affects various physiological systems, particularly male reproductive health. Research indicates that T2DM increases the risk of retrograde ejaculation, impairing sexual function and fertility. Dysregulation of lysyl oxidase (LOX) has been linked to diabetes-related complications in the male reproductive system. However, its role in seminal vesicle remains unclear. This study investigates LOX’s involvement in diabetes-related seminal vesicle pathology using human and mouse models. We assessed LOX expression in the seminal vesicles of men with T2DM and created a T2DM mouse model to observe changes. Our findings revealed elevated LOX expression in the seminal vesicles of T2DM men, accompanied by epithelial atrophy and fibrosis. Similarly, T2DM mice displayed significant atrophy and fibrosis of the seminal vesicles, correlated with increased LOX levels. Treatment with the LOX inhibitor, β-aminopropionitrile (BANP), significantly improved extracellular matrix remodeling and normalized the architecture of the seminal vesicles. Besides, LOX inhibition led to a significant reduction in T lymphocyte infiltration and apoptosis in the seminal vesicle epithelium of T2DM mice.These results highlight LOX’s critical role in seminal vesicle fibrosis associated with T2DM. Targeting LOX may provide a promising therapeutic strategy to alleviate reproductive complications and preserve reproductive health in men with T2DM.

Natural ovarian aging is one of the major causes for declining fertility in female animals, which has become an insurmountable issue in human reproduction clinics and assisted reproductive technology procedures. Nevertheless, the molecular basis of oocyte aging remains poorly understood, and feasible improvement strategies are unavailable. In the present study, in vivo supplementation of pyrroloquinoline-quinone effectively elevated the fecundity of reproductively aged mice by balancing hormonal secretion, harmonizing the estrus cycle, and eliminating ovarian fibrosis. Moreover, oocyte quality also increased in aged mice after pyrroloquinoline-quinone administration from various aspects, including nuclear and cytoplasmic maturation competency, fertilization capacity, and pre-implantation embryonic development potential. Transcriptomic analysis identified target pathways that might mediate pyrroloquinoline-quinone’s effects in aged oocytes. Specifically, it was demonstrated that pyrroloquinoline-quinone supplementation restored the mitochondrial dynamics and lysosomal function to remove excessive reactive oxygen species and suppress apoptosis in aged oocytes. Jointly, these findings demonstrate pyrroloquinoline-quinone administration is an efficacious method to restore the compromised ovary function and damaged oocyte quality in reproductively aged mice, which might be a potential clinical therapy for women of advanced maternal age with infertility.

Oxidative stress (OS) is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy. However, the OS-associated therapeutic target for esophageal squamous cell carcinoma (ESCC) remains unconfirmed. In our study, gene expression data of ESCC and clinical information from public databases were downloaded. Through LASSO-Cox regression analysis, a risk score (RS) signature map of prognosis was constructed and performed external verification with the GSE53625 cohort. The ESTIMATE, xCell, CIBERSORT, TIMER, and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment (IM). Afterward, functional enrichment analysis clarified the underlying mechanism of the model. Nomogram was utilized for forecasting the survival rate of individual ESCC cases. As a result, we successfully constructed an OS-related genes (OSRGs) model and found that the survival rate of high-risk groups was lower than that of low-risk groups. The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further. According to independent prognostic analysis, the RS was identified as an independent risk factor for ESCC. The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients. qRT-PCR detection demonstrated increased expression of MPC1, COX6C, CYB5R3, CASP7, and CYCS in esophageal cancer patients. In conclusion, we have constructed an OSRGs model for ESCC to predict patients’ prognosis, offering a novel insight into the potential application of the OSRGs model in ESCC.