Human umbilical cord mesenchymal stem cells derived extracellular vesicles alleviate salpingitis by promoting M1-to-M2 transformation.

Background: With an increasing number of patients experiencing infertility due to chronic salpingitis after Chlamydia trachomatis (CT) infection, there is an unmet need for tissue repair or regeneration therapies. Treatment with human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EV) provides an attractive cell-free therapeutic approach. Methods: In this study, we investigated the alleviating effect of hucMSC-EV on tubal inflammatory infertility caused by CT using in vivo animal experiments. Furthermore, we examined the effect of hucMSC-EV on inducing macrophage polarization to explore the molecular mechanism. Results: Our results showed that tubal inflammatory infertility caused by Chlamydia infection was significantly alleviated in the hucMSC-EV treatment group compared with the control group. Further mechanistic experiments showed that the application of hucMSC-EV induced macrophage polarization from the M1 to the M2 type via the NF-κB signaling pathway, improved the local inflammatory microenvironment of fallopian tubes and inhibited tube inflammation. Conclusion: We conclude that this approach represents a promising cell-free avenue to ameliorate infertility due to chronic salpingitis.

PTH (1-34) enhances the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes by inhibiting proinflammatory cytokines expression on OA chondrocyte repair in vitro.

BACKGROUND: The effects of bone marrow mesenchymal stem cells (BMSCs) during the treatment of cartilage damage have been proven to be attributed to paracrine mechanisms, particularly the effect of exosomes. Exosomes from different batches are inhomogeneous, and different treatment effects are observed between samples. The purpose of this research was to find more effective and homogeneous exosomes for the repair of chondrocytes in osteoarthritis (OA). We observed the potential effects and possible mechanisms of exosomes derived from parathyroid hormone (PTH) (1-34)-preconditioned BMSCs (ExoPTH) in the alleviation of OA. MATERIALS AND METHODS: Exosomes derived from BMSCs (ExoBMSC) and ExoPTH were isolated by differential centrifugation. Primary rat chondrocytes were used to establish the OA model by interleukin 1 beta (IL-1ß) in vitro. The effects of these two types of exosomes on OA chondrocyte proliferation, migration, apoptosis, and extracellular matrix formation were measured and compared. We observed changes in IL-2, TNF-α, and IL-6 levels via Western blotting (WB), and quantitative real-time PCR (qRT-PCR). RESULTS: We successfully extracted ExoBMSC and ExoPTH and established an IL-1ß-induced OA model in primary chondrocytes from rats. Our study showed that IL-2, TNF-α, and IL-6 levels increased significantly in OA chondrocytes; however, both ExoBMSC and ExoPTH reduced the levels of IL-2, TNF-α, and IL-6. In addition, ExoPTH exhibited stronger anti-inflammatory effects. ExoPTH had a more marked effect on proliferation, migration, and production of the extracellular matrix (Col-II) in OA chondrocytes than ExoBMSC at 24 h. CONCLUSION: ExoPTH increased the migration, proliferation, and chondral matrix formation of OA chondrocytes in vitro. In OA chondrocyte therapy, the potential mechanism of ExoPTH might involve the inhibition of production of proinflammatory cytokines. Although the two types of exosomes had some similar effects, most effects of ExoPTH were better than those of ExoBMSC, so ExoPTH may have a better ability to alleviate OA.

KMT2A regulates cervical cancer cell growth through targeting VDAC1.

Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of KMT2A in cervical cancer remains unknown. Here, we demonstrated that KMT2A regulated cervical cancer growth via targeting VADC1. Knockdown of KMT2A significantly suppressed cell proliferation and migration and induced apoptosis in cervical cancer cells, accompanying with activation of PARP/caspase pathway and inhibition of VADC1. Overexpression of VDAC1 reversed the KMT2A knockdown-mediated regulation of cell proliferation, migration and apoptosis. The in vivo results from a cervical cancer xenograft mouse model also validated that KMT2A knockdown suppressed tumor growth by inhibiting VDAC1, whereas KMT2A overexpression promoted cervical cancer growth. Moreover, analyses of Biewenga cervix database and clinical samples showed that both KMT2A and VDAC1 were upregulated in cervix squamous cell carcinoma compared with cervix uteri tissues, and their expression was negatively correlated with the differentiation grade of cervical cancer. Our results therefore indicated that the KMT2A/VDAC1 signaling axis may be a potential new mechanism of cervical carcinogenesis.