Introduction: Therapeutic potentials of mesenchymal stem cells (MSCs) from different sources have been evaluated in pre-clinical and clinical settings. Although MSCs from different sources share MSC-specific characteristics and functions, inconsistent or controversial results of pre-clinical and clinical applications of such cells are frequently reported. This may be partially due to the fact that MSCs isolated from different origins may differentially express some functions not typical for MSCs, and hence have different therapeutic potentials. The aim of this study is to investigate the differences in human placental MSCs (P-MSCs) of fetal and maternal origins in the aspects of clinical importance. Methods: P-MSCs of fetal and maternal origins isolated from normal term placentas were characterized for their typical phenotype as well as their expression of receptors and growth factors of clinic interests. P-MSCs that preferentially express hepatocyte growth factor (HGF) and CD200 were evaluated for their therapeutic potentials in models of angiogenesis and allogeneic skin transplantation, in comparison with their HGF and CD200 negative partners. Results: Although all P-MSCs express typical MSC phenotype, fetal but not maternal P-MSCs express high levels of CD200 and HGF. Compared with HGF and CD200 negative P-MSCs, HGF and CD200 positive cells demonstrated significantly high potentials in promoting angiogenesis in vitro and increasing immunosuppressive function in vivo. These therapeutic potentials were at least in part due to their differences in HGF and CD200 expression, respectively. Conclusions: We conclude that MSC origins may have significant impact on the therapeutic potentials of such cells, and should be taken into consideration in clinical applications.

The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry) box-containing) family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer.

Background: Mesenchymal stem cells (MSCs) are promising remedies for various inflammatory disease including pulmonary fibrosis (PF). However, the properties of MSCs in PF pathological microenvironment remain unclear. In this study, the efficacy of autophagy in placental mesenchymal stem cells of fetal origin (fPMSCs) in either IL-1 beta treatment or BLM induced pulmonary fibrosis mice model was examined. Methods: The characteristic of fPMSCs was identified by morphological observation, flow cytometry and dif-ferentiation potential. In vitro experiments, fPMSCs were stimulated with IL-1 beta, to mimic inflammatory microenvironment of pulmonary fibrosis. The immunosuppressive properties and autophagic function in fPMSCs treated with IL-1 beta were evaluated by both macrophage cells THP-1 activation and the expression of CD200 situation, autophagy marker and MAPK signaling pathway. The in vivo anti-fibrotic activity of fPMSCs inter-fering autophagy was evaluated by using BLM induced pulmonary fibrosis mice model. Results: fPMSCs belonged to CD73+CD90+CD105+/CD14- CD34-CD45-HLA-DR- cells, and capable differentiation to adipogenic, osteogenic and chondrogenic cells. In addition, immunoinhibitory activity of fPMSCs for macrophage was restrained by IL-1 beta treatment in CD200 dependent manner. Suppression of autophagy by sh-Atg5 lentivirus increased the expression of CD200 and ratio of CD200 positive fPMSCs, and enhanced fPMSCs immunosuppression for THP-1 activation. Mechanistically, IL-1 beta induced autophagy regulated by p38 signaling cascade. In vivo, autophagy inhibition induced by Atg5 knockdown in fPMSCs resulted in strengthening anti -fibrotic effects on PF mice model. Conclusions: Collectively, autophagy derived from inflammatory microenvironment hampered the immu-noinhibitory properties of MSCs. Based on this, adjustment of autophagy may be a valid approach to facilitate their immunomodulatory and anti-fibrotic efficacy. Superscript/Subscript Available</comment

Using bioinformatics machine learning methods, our research aims to identify the potential key genes associated with Lung adenocarcinoma (LUAD). We obtained two gene expression profiling microarrays (GSE68571 and GSE74706) from the public Gene Expression Omnibus (GEO) database at the National Centre for Biotechnology Information (NCBI). The purpose was to identify Differentially Expressed Genes (DEGs) between the lung adenocarcinoma group and the healthy control group. The limma R package in R was utilized for this analysis. For the differential gene diagnosis of lung adenocarcinoma, we employed the least absolute shrinkage and selection operator (LASSO) regression and SVM-RFE screening crossover. To evaluate the performance, ROC curves were plotted. We performed immuno-infiltration analysis using CIBERSORT. Finally, we validated the key genes through qRT-PCR and Western-blot verification, then downregulated MMP17 gene expression, upregulated SH3GL2 gene expression, and performed CCK8 experiments. A total of 32 Differentially Expressed Genes (DEGs) were identified. Two diagnostic marker genes, SH3GL2 and MMP17, were selected by employing LASSO and SVM-RFE machine learning methods. In Lung adenocarcinoma cells, the expression of MMP17 was observed to be elevated compared to normal lung epithelial cells in the control group (P < 0.05). In contrast, a down-regulation of SH3GL2 was found in Lung adenocarcinoma cells (P < 0.05). Finally, we downregulated MMP17 and upregulated SH3GL2 gene expression, then the CCK8 showed that the proliferation of both lung cancer cells was inhibited. SH3GL2 and MMP17 are expected to be potential biomarkers for Lung adenocarcinoma.

Mesenchymal stem cell (MSC) therapy represents a promising strategy for pulmonary fibrosis (PF) treatment, with hepatocyte growth factor (HGF) serving as a key mediator of MSC-mediated protection. However, the therapeutic efficacy of MSCs is limited by the complex PF microenvironment, and the mechanisms underlying this limitation remain unclear. This study investigates how the PF pathological microenvironment modulates the antifibrotic potential of placental mesenchymal stem cells of fetal origin (fPMSCs) through HGF regulation and elucidates the molecular mechanisms involved. Morphological analysis, flow cytometry, and multilineage differentiation assays were employed to characterize fPMSCs. Transforming growth factor-β1 (TGF-β1) was employed to simulate the PF microenvironment and activate fPMSCs in vitro. ELISA and Western blotting were used to analyze HGF expression, autophagy markers, and Smad signaling. Autophagosome formation was visualized via confocal microscopy and transmission electron microscopy. Co-immunoprecipitation (Co-IP) assays were performed to assess the interaction between p62 and HGF. The antifibrotic function of fPMSCs was further evaluated using a transwell co-culture system with MRC-5 fibroblasts in vitro and a bleomycin-induced PF mouse model in vivo. Phenotypic characterization confirmed that fPMSCs exhibited canonical MSC morphology, expressed CD73/CD90/CD105, lacked CD14/CD34/CD45/HLA-DR, and differentiated into adipogenic, osteogenic, and chondrogenic lineages. TGF-β1 treatment robustly downregulated the antifibrotic capacity, HGF protein expression, and paracrine secretion in fPMSCs. Recombinant HGF enhanced antifibrotic effects, while an HGF-neutralizing antibody abolished them. TGF-β1 induced autophagy in fPMSCs, promoting HGF degradation via p62 interaction and impairing antifibrotic function in vitro and in vivo. Mechanistically, Smad3 phosphorylation mediated the regulation of autophagy and HGF expression in TGF-β1-treated fPMSCs. Our findings demonstrate that TGF-β1 impairs the antifibrotic function of fPMSCs via autophagy-dependent HGF degradation and Smad3 signaling. Conversely, autophagy inhibition restores HGF levels and enhances fPMSCs’ therapeutic efficacy in a preclinical PF model. Targeting autophagy inhibition emerges as a promising therapeutic strategy to counteract pulmonary fibrosis.

Breast cancer patients often have a poor prognosis largely due to lack of effective targeted therapy. It is now well established that monosaccharide enhances growth retardation and chemotherapy sensitivity in tumor cells. We investigated whether d-arabinose has capability to restrict the proliferation of tumor cells and its mechanism. Here, we report that d-arabinose induced cytotoxicity is modulated by autophagy and p38 MAPK signaling pathway in breast cancer cell lines. The proliferation of cells was evaluated by CCK-8 and Colony formation assay. The distribution of cells in cell cycle phases was analyzed by flow cytometry. Cell cycle, autophagy and MAPK signaling related proteins were detected by western blotting. Mouse xenograft model was used to evaluate the efficacy of d-arabinose in vivo. The proliferation of cells was dramatically inhibited by d-arabinose exposure in a dose-dependent manner, which was relevant to cell cycle arrest, as demonstrated by G2/M cell cycle restriction and ectopic expression of cell cycle related proteins. Mechanistically, we further identified that d-arabinose is positively associated with autophagy and the activation of the p38 MAPK signaling in breast cancer. In contrast, 3-Ma or SB203580, the inhibitor of autophagy or p38 MAPK, reversed the efficacy of d-arabinose. Additionally, d-arabinose in vivo treatment could significantly inhibit xenograft growth of breast cancer cells. Our findings were the first to reveal that d-arabinose triggered cell cycle arrest by inducing autophagy through the activation of p38 MAPK signaling pathway in breast cancer cells.