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Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing. In vitro coculture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA. [ABSTRACT FROM AUTHOR]

Background. With an enormous amount of research concerning kidney cancer being conducted, various treatments have been applied to its cure. However, high recurrence and metastasis rates continue to pose a threat to the survival of patients with kidney renal clear cell carcinoma (KIRC). Methods. Data from The Cancer Genome Atlas were downloaded, and a series of analyses were performed, including differential analysis, Cox analysis, weighted gene coexpression network analysis, least absolute shrinkage and selection operator analysis, multivariate Cox analysis, survival analysis, and receiver operating characteristic curve and functional enrichment analysis. Results. A total of 5,777 differentially expressed genes were identified from the differential analysis. The Cox analysis showed 1,853 significant genes (P < 0.01). Weighted gene coexpression network analysis revealed that 226 genes in the module were related to clinical parameters, including Tumor-Node-Metastasis (TNM) staging. Least absolute shrinkage and selection operator and multivariate Cox analyses suggested that four genes (CDKL2, LRFN1, STAT2, and SOWAHB) had a potential function in predicting the survival time of patients with KIRC. Survival analysis uncovered that a high risk of these four genes was associated with an unfavorable prognosis. Receiver operating characteristic curve analysis further confirmed the accuracy of the risk score model. The analysis of clinicopathological parameters of the four identified genes revealed that they were associated with the progression of KIRC. Conclusion. The gene expression model consisting of CDKL2, LRFN1, STAT2, and SOWAHB is a promising tool for predicting the prognosis of patients with KIRC. The results of this study may provide insights into the diagnosis and treatment of KIRC. [ABSTRACT FROM AUTHOR]

High-altitude deacclimatization syndrome (HADAS) is involved in hypoxia-reoxygenation injury and inflammatory response, induced a series of symptoms, and has emerged as a severe public health issue. Here, we investigated the mechanism as well as potential means to prevent HADAS using Shenqi pollen capsules (SPCs) in subjects with HADAS in a multicenter, double-blinded, randomized, placebo-controlled study. All subjects were at the same high altitude (3650 m) for 4-8 months before returning to lower altitudes. Subjects (n = 288) in 20 clusters were diagnosed with mild or moderate HADAS on the third day of the study. We randomly allocated 20 clusters of subjects (1 : 1) to receive SPCs or a placebo for 7 weeks, and they were then followed up to the 14th week. The primary endpoints were subjects' HADAS scores recorded during the 14 weeks of follow-up. Compared with the placebo, SPC treatment significantly decreased the subjects' HADAS scores and reduced the incidence of symptom persistence. SPC therapy also reduced the serum levels of CK, CK-MB, LDH, IL-17A, TNF-α, and miR-155 and elevated IL-10 and miR-21 levels. We thus demonstrate that SPCs effectively ameliorated HADAS symptoms in these subjects via suppression of the hypoxia-reoxygenation injury and inflammatory response. [ABSTRACT FROM AUTHOR]