ABSTRACT
Erectile dysfunction (ED) is an adverse side effect of pelvic surgery with no effective treatment. In this study, it is explored whether melatonin could improve the therapeutic effects of small extracellular vesicles (sEVs), derived from mesenchymal stem cells (MSCs), on cavernous nerve injury (CNI) ED, and the underlying mechanisms are investigated. The sEVs from melatonin-pretreated MSCs (MT-EVs) and MSCs (NC-EVs) are isolated and applied to CNI ED. Transplantation of MT-EVs remarkably increases erectile function and reduces phenotypic modulation in CNI ED rats. The therapeutic effects of MT-EVs are superior to those of NC-EVs. Sequencing implies that miR-10a-3p is enriched in MT-EVs, and directly targets the protein kinase inhibitor α (PKIA). After the suppression of miR-10a-3p, the therapeutic actions of MT-EVs are abolished, but are rescued by PKIA. Similarly, RhoA/ROCK is inhibited by MT-EVs, but this action is reversed by suppressing miR-10a-3p, accompanied by corresponding changes in PKIA. In conclusion, transplantation of MT-EVs could significantly alleviate CNI ED. MT-EVs may relieve the phenotypic modulation of the corpora cavernosum smooth muscle cells via the miR-10a-3p/PKIA/RhoA/ROCK signaling axis. These nanovesicles should be potential therapeutic vectors or bioactive materials for CNI ED.
Subject(s)
Erectile Dysfunction , Extracellular Vesicles , Melatonin , Mesenchymal Stem Cells , MicroRNAs , Male , Humans , Rats , Animals , Erectile Dysfunction/drug therapy , Erectile Dysfunction/metabolism , Melatonin/pharmacology , Melatonin/metabolism , Melatonin/therapeutic use , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
OBJECTIVES: To determine the prevalence of SENV infections among blood donors in central Taiwan and to clarify the relationship between these infections and elevated alanine aminotransaminase (ALT) values. METHODS: DNA was extracted from plasma of 200 blood donors and amplified by seminested PCR. RESULTS: For all donors, the prevalence of SENV-D was 32%, and of SENV-H was 30.5%. Prevalence of mixed SENV-D/H infection was 11.5% and of SENV-D and/or SENV-H (SENV-D/H) was 51%. Infections were not associated with age, gender, or raised ALT values. CONCLUSIONS: SENV-D and SENV-H infections are common among blood donors in central Taiwan but are unlikely to contribute to abnormal ALT values.
