Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro.

Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%- 50% of all infertility cases. Nonobstructive azoospermia (NOA) is the most severe type of male infertility. Human umbilical cord mesenchymal stem cell (hUCMSC) exosomes enhance proliferation and migration, playing crucial roles in tissue and organ injury repair. However, whether hUCMSC exosomes impacting on NOA caused by chemotherapeutic agents remains unknown. This study aimed to explore the functional restoration and mechanism of hUCMSC exosomes on busulfan-induced injury in GC-1 spg cells and ICR mouse testes. Our results revealed that hUCMSC exosomes effectively promoted the proliferation and migration of busulfan-treated GC-1 spg cells. Additionally, oxidative stress and apoptosis were significantly reduced when hUCMSC exosomes were treated. Furthermore, the injection of hUCMSC exosomes into the testes of ICR mice treated with busulfan upregulated the expression of mouse germ cell-specific genes, such as vasa, miwi, Stra8 and Dazl. Moreover, the expression of cellular junction- and cytoskeleton-related genes, including connexin 43, ICAM-1, ß-catenin and androgen receptor (AR), was increased in the testicular tissues treated with exosomes. Western blot analysis demonstrated significant downregulation of apoptosis-associated proteins, such as bax and caspase-3, and upregulation of bcl-2 in the mouse testicular tissues injected with hUCMSC exosomes. Further, the spermatogenesis in the experimental group of mice injected with exosomes showed partial restoration of spermatogenesis compared to the busulfan-treated group. Collectively, these findings provide evidence for the potential clinical applications of hUCMSC exosomes in cell repair and open up new avenues for the clinical treatment of NOA.

Identification of a novel PANoptosis-related gene signature for predicting the prognosis in clear cell renal cell carcinoma.

PANoptosis has been shown to play an important role in tumorigenesis and gain more attention. Yet, the prognostic significance of PANoptosis-related genes has not been investigated more in clear cell renal cell carcinoma (ccRCC). The aim of this research was designed to identify and create a signature of PANoptosis-related genes which was expected to predict prognosis of ccRCC more effectively. The transcriptome data and clinical information were collected from The Cancer Genome Atlas database and the Gene Expression Omnibus database. Optimal differentially expressed PANoptosis-related genes, which were closely associated with prognosis and employed to construct a risk score, were extracted by univariate Cox analysis, least absolute shrinkage and selection operator Cox regression and multivariate Cox analysis. We performed Kaplan-Meier survival analysis and time-dependent receiver operating characteristic curves to complete this process. By adopting univariate and multivariate analysis, the constructed risk score was assessed to verify whether it could be taken as an independent contributor for prognosis. Moreover, we created a nomogram in order to predict overall survival (OS) of ccRCC. Five differentially expressed PANoptosis-related genes were screened out and used to construct a risk score. Our results showed that ccRCC patients with high risk score had a poor prognosis and shorter OS. The results of Kaplan-Meier curves and the area under the receiver operating characteristic curves of 1-, 3-, and 5-year OS indicated that the prediction performance was satisfactory. Additionally, the risk model could be taken as an independent prognostic factor in training and validation cohorts. The nomogram exhibited excellent reliability in predicting OS, which was validated by calibration curves. We identified 5 PANoptosis-related genes, which were used to construct a risk score and a nomogram for prognostic prediction with reliable predictive capability. The present study may provide new potential therapeutic targets and precise treatment strategies for ccRCC.

Functional prediction and profiling of exosomal circRNAs derived from seminal plasma for the diagnosis and treatment of oligoasthenospermia.

Oligoasthenospermia (OAZ) is the most common element contributing to male infertility. However, the etiology of OAZ remains unknown in the majority of cases. Growing evidence indicates that exosomal circular (circ)RNAs may exhibit potential as biological markers for the detection of various disorders. The available information on exosomes derived from seminal plasma is limited. The present study investigated the composition and role of circRNAs in exosomes isolated from seminal plasma of patients with OAZ. Exosomes were isolated from the seminal plasma of 12 patients with OAZ and 12 matched healthy controls. Thereafter, RNA sequencing was performed using exosomes from both groups to identify circRNAs associated with OAZ. The sequencing data revealed a total of 14,991 circRNAs. Among these, 7,635 were upregulated and 7,356 were downregulated in patients with OAZ. Gene Ontology functional enrichment analysis revealed that the differentially expressed exosomal circRNAs were primarily enriched in 'protein binding', 'intracellular organelles' and 'cellular metabolism'. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed exosomal circRNAs were enriched in 'ubiquitin-mediated proteolysis', 'endocytosis' and 'RNA transport', which are involved in spermatogenesis-related pathways. Then seven differentially expressed circRNAs were predicted and validated as putative upstream targets and their target genes also were detected by reverse transcription-quantitative PCR. CircRNA-microRNA-mRNA network was constructed to predict their potential functions. The findings provide a preliminary foundation for identifying the potential diagnostic value of critical exosomal circRNAs involved in OAZ.