Bone marrow–derived mesenchymal stem cells (BMSCs) have been recently reported to play a variety of vital roles in organ and tissue damage repair, mainly via potent paracrine activity, including secreting extracellular vesicles, such as exosomes, that serve as mediators facilitating intercellular communication and reprogramming recipient cells by delivering their contents to target cells. However, the underlying mechanisms are diverse and complex, and the influencing characteristics have rarely been studied. Accordingly, we designed this study to explore the time dependence of the effects of exosomes derived from BMSCs (BMexos) on renal ischemia‐reperfusion (I/R) injury and the underlying mechanisms associated with the reperfusion time. Impressively, our study is the first to find that BMexos protected against renal I/R injury in vitro and in vivo at the very early reperfusion stages, especially 4–8 h after reperfusion in vitro and 8–16 h after reperfusion in vivo . Interestingly, we simultaneously found that endoplasmic reticulum (ER) stress was significantly suppressed following the administration of BMexos in vitro and in vivo with a similar time dependence. Additionally, we discovered that miR‐199a‐5p, which was abundant in the BMSCs, was transferred into renal tubular epithelial cells (NRK‐52E) in a time‐dependent manner and significantly inhibited I/R‐induced ER stress by targeting binding immunoglobulin protein (BIP). Cocultivation with miR‐199a‐5p‐overexpressing BMSCs amplified the suppression of ER stress and further protected against I/R injury. However, coculture with miR‐199a‐5p‐knockdown BMSCs obviously increased ER stress and reversed the BMexos‐induced protection, and silencing BIP by small interfering RNA–1098 in NRK‐52E inhibited these effects. This study provides evidence that administering BMexos at the very early reperfusion stages significantly protects against renal I/R injury, and ER stress is closely linked to this protection. These results suggest a novel therapeutic strategy during the very early reperfusion stages of renal I/R injury.—Wang, C., Zhu, G., He, W., Yin, H., Lin, F., Gou, X., Li, X. BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages. FASEB J. 33, 5440–5456 (2019). www.fasebj.org

Background: Due to its high infectivity and concealment, the coronavirus disease 2019 (COVID-19) outbreak that occurred in Wuhan attracted global attention. A special nursing group of transdisciplinary nurses (TNs) who had not worked in respiratory medicine, infection departments, or emergency and intensive medicine but who accounted for a large proportion of all nurses also drew our attention. Few studies have examined this special group of TNs. Therefore, this study collected the experiences and views of TNs at the forefront of the COVID-19 outbreak to investigate their potential problems. Results: Twenty-five TNs and 19 nurses with experience in infectious diseases (non-TNs) were enrolled in the study. Compared with non-TNs, TNs showed higher levels of perceived stress and relatively less perceived social support. For TNs, the ambiguous roles, transition of operating mode, unfamiliar work content, and reversal of their daily schedule were the most common vocational problems. Additionally, most TNs had psychological problems such as anxiety, pain and insomnia. The incomprehension of parents, concern for family members and long-term isolation were the most common causes of psychological stress. Conclusion: This survey is the first to focus on the group of TNs at the forefront of the COVID-19 outbreak and to investigate their experiences, vocational issues and psychological stresses qualitatively and quantificationally. We found that TNs had more perceived stress and less perceived social support than non-TNs. The vocational and psychological issues of TNs should be highlighted. These findings identify important issues and offer insights into the underlying issues to help TNs ultimately win the battle against novel coronavirus epidemics. Methods: Semi-structured and face-to-face individual interviews and quantitative assessments were conducted. The Braun Clarke Thematic Analysis method and the strategy outlined by Miles and Huberman were used in the data analysis process of the qualitative study. The perceived stress scale and perceived social support scale were utilized to quantificationally evaluate the perceived stress level and the amount of perceived social support. Both qualitative and quantitative methods were adopted to assess the vocational and psychological perceptions and issues.

Background: Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in urogenital system, and the clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. Immune related long non-coding RNAs (IRlncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IRlncRs analysis based on abundant ccRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field. Methods: Based on the TCGA dataset, we integrated the expression profiles of IRlncRs and overall survival (OS) in the 611 ccRCC patients. The immune score of each sample was calculated based on the expression level of immune-related genes and used to identify the most meaningful IRlncRs. Survival-related IRlncRs (sIRlncRs) was estimated by calculating the algorithm of difference and COX regression analysis in ccRCC patients. Based on the median immune-related risk score (IRRS) developed from the screened sIRlncRs, the high-risk and low-risk components were distinguished. Functional annotation was detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor was evaluated by microenvironment cell population records. The expression levels of three sIRlncRs were verified in various tissues and cell lines. Results: A total of 39 IRlncRs were collected by Pearson correlation analyses among immune score and the lncRNA expression. A total of 7 sIRlncRs were significantly associated with the clinical outcomes of ccRCC patients. Three sIRlncRs (ATP1A1-AS1, IL10RB-DT and MELTF-AS1) with the most significant prognostic values were enrolled to build the IRRS model in which the OS of in the high-risk group was shorter than that in the low-risk group. The IRRS was identified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group illustrated different distributions in PCA and different immune status in GSEA. Besides, we found the more significant expression in certain ccRCC cell lines and tumor tissues of ccRCC patients compared with the HK-2 and adjacent tissues respectively. Additionally, the expression levels of lncR-MELTF-AS1 and IL10RB-DT were remarkably enhanced along the more advanced T-stages, but the lncR-ATP1A1-AS1 showed the inverse gradient. Conclusion: Our results demonstrate some sIRlncRs with remark clinical relevance show the latent monitoring and prognosis values for ccRCC patients and may provide new insight in immunological researches and treatment strategies of ccRCC patients.

Background: Papillary renal cell carcinoma (pRCC) was the 2nd most common subtype, accounting for approximately 15% incidence of renal cell carcinoma (RCC). Immune related long non-coding RNAs (IR-lncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IR-lncRs analysis based on abundant pRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field.

Background: Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in urogenital system, and the clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. Immune related long non-coding RNAs (IRlncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IRlncRs analysis based on abundant ccRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field. Methods: Based on the TCGA dataset, we integrated the expression profiles of IRlncRs and overall survival (OS) in the 611 ccRCC patients. The immune score of each sample was calculated based on the expression level of immune-related genes and used to identify the most meaningful IRlncRs. Survival-related IRlncRs (sIRlncRs) was estimated by calculating the algorithm of difference and COX regression analysis in ccRCC patients. Based on the median immune-related risk score (IRRS) developed from the screened sIRlncRs, the high-risk and low-risk components were distinguished. Functional annotation was detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor was evaluated by microenvironment cell population records. The expression levels of three sIRlncRs were verified in various tissues and cell lines.Results: A total of 39 IRlncRs were collected by Pearson correlation analyses among immune score and the lncRNA expression. A total of 7 sIRlncRs were significantly associated with the clinical outcomes of ccRCC patients. Three sIRlncRs (ATP1A1-AS1, IL10RB-DT and MELTF-AS1) with the most significant prognostic values were enrolled to build the IRRS model in which the OS of in the high-risk group was shorter than that in the low-risk group. The IRRS was identified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group illustrated different distributions in PCA and different immune status in GSEA. Besides, we found the more significant expression in certain ccRCC cell lines and tumor tissues of ccRCC patients compared with the HK-2 and adjacent tissues respectively. Additionally, the expression levels of lncR-MELTF-AS1 and IL10RB-DT were remarkably enhanced along the more advanced T-stages, but the lncR-ATP1A1-AS1 showed the inverse gradient.Conclusion: Our results demonstrate some sIRlncRs with remark clinical relevance show the latent monitoring and prognosis values for ccRCC patients and may provide new insight in immunological researches and treatment strategies of ccRCC patients.