Acute lung injury (ALI), an increasingly devastating human disorder, is characterized by a multitude of lung changes arising from a wide variety of lung injuries. Viral infection is the main cause of morbidity and mortality in ALI and acute respiratory distress syndrome (ARDS) patients. In particular, influenza virus, coronavirus, and other respiratory viruses circulate in nature in various animal species and can cause severe and rapidly spread human infections. Although scientific advancements have allowed for rapid progress to be made to understand the pathogenesis and develop therapeutics after each viral pandemic, few effective methods to treat virus-induced ALI have been described. Recently, stem cell therapy has been widely used in the treatment of various diseases, including ALI. In this review, we detail the present stem cell-based therapeutics for lung injury caused by influenza virus and the outlook for the future state of stem cell therapy to deal with emerging influenza and coronaviruses.
As is previously reported, mesenchymal stem cells have potential ability to differentiate into osteocytes. However, the underlying mechanism during this biological process is poorly understood. In the present study, we identify a novel long non‐coding RNA named HOXA‐AS2 as a critical regulator during the formation of osteogenesis. Attenuation of HOXA‐AS2 can reduce the calcium deposition and repress the alkaline phosphatase activity. Moreover, the expressions of osteogenic marker genes are markedly downregulated after HOXA‐AS2 depletion. Mechanistically, we found HOXA‐AS2 can regulate the transcriptional activity of NF‐κB, a critical inhibitor of osteogenesis. More importantly, HOXA‐AS2 knockdown could result in the transcriptional repression of the osteogenic master transcription factor SP7 by a NF‐κB/HDAC2‐coordinated H3K27 deacetylation mechanism. Based on these studies, we conclude that HOXA‐AS2 may serve as a promising therapeutic target for bone tissue repair and regeneration in the near future.
Background/aimsMenstrual blood-derived endometrial stem cells (MenSCs) emerge as an ideal source for cell-based treatment in regenerative medicine and immunotherapy. However, the major obstacle is the low survival rate in tissues and the limited expansion number. Autophagy is an intracellular metabolic self-degradative process which plays important roles in normal cellular division and survival, and the present study aimed to explore the related mechanisms between autophagy and survival of MenSCs in vitro and in vivo.MethodsThe MenSCs were obtained from menstrual blood procured from healthy female donors. In vitro, MenSCs were exposed to rapamycin and Earle’s balanced salts solution (EBSS). We evaluated the MenSCs immunophenotypic cell cycle distribution by propidium iodide (PI) staining and cell apoptosis by Annexin V/PI staining as well as their proliferative potential by the MTT assay. We also assessed the expression of genes associated with the cell cycle and Gsk3β signaling pathway by western blot analysis. We depressed Atg5 and Gsk3β expression by short hairpin RNA (shRNA) and undertook the experiments. Moreover, the labeled MenSCs were observed and counted with DiI after transplantation into the mice via the tail vein by microscopy in vivo.ResultsIn vitro, rapamycin and starvation induced autophagy of MenSCs. Hyperactive autophagy significantly induced G0/G1 arrest and slightly promoted apoptosis of MenSCs. Meanwhile, autophagy could stimulate p-GSK3β expression in MenSCs. Further, knockdown GSK3β can accelerate the proliferation of MenSCs by shRNA and CHIR99021. Moreover, the shGSK3β MenSCs showed strong proliferative activity in vitro and in vivo.ConclusionsOur results indicate that autophagy induced G0/G1 arrest and apoptosis of MenSCs via GSK3β/β-catenin pathway. Inhibiting autophagy or reduced GSK3β levels may improve survival rate in vivo, thus playing roles in MenSCs therapy.
Background: Research into the pathogenesis of endometriosis (EMs) would substantially promote its effective treatment and early diagnosis. However, the aetiology of EMs is poorly understood and controversial despite the progress in EMs research in the last several decades. Currently, accumulating evidence has shed light on the importance of endometrial stem cells (EnSCs) residing in the basal layer of endometrium in the establishment and progression of endometriotic lesions. Therefore, we aimed to identify the differences between EnSCs isolated from the ectopic lesions of EMs patients (EnSC-EM-EC) and EnSCs isolated from eutopic endometrium of control group (EnSC-Control). We further performed preliminary exploration of the potential signalling pathways involved in the above abnormalities. Methods: EnSC-EM-EC (n = 12) and EnSC-Control (n = 13) were successfully isolated. Then, the proliferative capacity, migratory capacity and angiogenic potential of EnSCs were evaluated by conventional MTT assay, flow cytometry, wound healing assay, transwell assay, tube formation assay and chick embryo chorioallantoic membrane assay respectively. The expression of 11 angiogenesis-associated biological factors and 11 cytokines secreted by EnSCs and 17 adhesion molecules expressed on EnSCs were determined by protein array assays respectively. Differentially expressed genes (DEGs) between EnSC-EM-EC and EnSC-Control were analysed by RNA-sequence.
Non‐alcoholic fatty liver disease (NAFLD), an increasingly devastating human disorder, is characterized by intrahepatic fat accumulation. Although important progress has been made in understanding NAFLD, the fundamental mechanisms involved in the pathogenesis of NAFLD have not been fully explained. The endo‐lysosomal trafficking network is central to lipid metabolism, protein degradation and signal transduction, which are involved in a variety of diseases. In recent years, many genes and pathways in the endo‐lysosomal trafficking network and involved in lysosomal biogenesis have been associated with the development and progression of NAFLD. Mutations of these genes and impaired signalling lead to dysfunction in multiple steps of the endo‐lysosomal network (endocytic trafficking, membrane fusion and lysosomal degradation), resulting in the accumulation of pathogenic proteins. In this review, we will focus on how alterations in these genes and pathways affect endo‐lysosomal trafficking as well as the pathophysiology of NAFLD.
Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
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