Background Mesenchymal stromal/stem cells (MSCs) have been intensively investigated in both pre-clinical and clinical studies. However, the therapeutic efficacy varies resulting from the heterogenicity of MSCs. Therefore, purifying the specific MSC subpopulation with specialized function is necessary for their therapeutic applications. Methods The large-scale RNA sequencing analysis was performed to identify potential cell markers for the mouse MSCs. Then, the immune suppression activities of the purified MSC subpopulation were assessed in vitro and in vivo. Results The TNFAIP6 (tumor necrosis factor alpha-induced protein 6) has been identified as a potential cell marker for mouse MSCs, irrespective of tissue origin and laboratory origin. The TNFAIP6+ mouse MSCs showed enhanced immune suppression activities and improved therapeutic effects on the mouse model of acute inflammation, resulting from faster response to immune stimulation. Conclusions Therefore, we have demonstrated that the TNFAIP6+ MSC subpopulation has enhanced immune suppression capabilities.

Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine, which exhibits strong anti-inflammatory, anti-viral and anti-tumor activities. The present work was devoted to elucidate the molecular and cellular mechanisms underlying the protective effects of Baicalin against diabetes-induced oxidative damage, inflammation and endothelial dysfunction. Diabetic mice, induced by streptozotocin (STZ), were treated with intraperitoneal Baicalin injections. Human umbilical vein endothelial cells (HUVECs) were cultured either in normal glucose (NG, 5.5 mM) or high glucose (HG, 33 mM) medium in the presence or absence of Baicalin for 72 h. We observed an obvious inhibition of hyperglycemia-triggered oxidative damage and inflammation in HUVECs and diabetic aortal vasculature by Baicalin, along with restoration of hyperglycemia-impaired nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway activity. However, the protective effects of Baicalin almost completely abolished in HUVECs transduced with shRNA against Nrf2, but not with nonsense shRNA. Mechanistic studies demonstrated that HG decreased Akt and GSK3B phosphorylation, restrained nuclear export of Fyn and nuclear localization of Nrf2, blunted Nrf2 downstream target genes and subsequently induced oxidative stress in HUVECs. However, those destructive cascades were well prevented by Baicalin in HUVECs. Furthermore, LY294002 and ML385 (inhibitor of PI3K and Nrf2) attenuated Baicalin-mediated Nrf2 activation and the ability of facilitates angiogenesis in vivo and ex vivo. Taken together, the endothelial protective effect of Baicalin under hyperglycemia condition could be partly attributed to its role in downregulating reactive oxygen species (ROS) and inflammation via the Akt/GSK3B/Fyn-mediated Nrf2 activation.

Diabetic vascular complications are closely associated with long‐term vascular dysfunction and poor neovascularization. Endothelial progenitor cells (EPCs) play pivotal roles in maintaining vascular homeostasis and triggering angiogenesis, and EPC dysfunction contributes to defective angiogenesis and resultant diabetic vascular complications. Fibroblast growth factor 21 (FGF21) has received substantial attention as a potential therapeutic agent for diabetes via regulating glucose and lipid metabolism. However, the effects of FGF21 on diabetic vascular complications remain unclear. In the present study, the in vivo results showed that FGF21 efficiently improved blood perfusion and ischaemic angiogenesis in both type 1 and type 2 diabetic mice, and these effects were accompanied by enhanced EPC mobilization and infiltration into ischaemic muscle tissues and increases in plasma stromal cell–derived factor‐1 concentration. The in vitro results revealed that FGF21 directly prevented EPC damage induced by high glucose, and the mechanistic studies demonstrated that nicotinamide adenine dinucleotide (NAD+) was dramatically decreased in EPCs challenged with high glucose, whereas FGF21 treatment significantly increased NAD+ content in an AMPK‐dependent manner, resulting in improved angiogenic capability of EPCs. These results indicate that FGF21 promotes ischaemic angiogenesis and the angiogenic ability of EPCs under diabetic conditions by activating the AMPK/NAD+ pathway.

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Circular RNAs (circRNAs) are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to investigate the roles and molecular mechanism underlying the effects of circ_0074673 in GDM. Exosomal morphology was visualized by transmission electron microscopy (TEM), while exosomal size and concentration were determined by nanoparticle tracking analysis (NTA). The expression of CD9 and CD63 was measured by western blotting. The levels of circ_0074673, miR-1200 and mesenchyme homeobox 2 (MEOX2) were determined by quantitative real-time polymerase chain reaction (qPCR). Cellular proliferation, migration, and angiogenesis were measured by Cell Counting Kit-8 (CCK-8), transwell, and tube formation assays, respectively. The binding relationship between circ_0074673 or MEOX2 and miR-1200 was evaluated by luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNApull-down assay. The results showed that exosomal size and concentration were greater in the umbilical cord blood of patients with GDM than in that of the healthy controls. The expression of circ_0074673 was upregulated in exosomes from GDM and in human umbilical vein endothelial cells (HUVECs) co-cultured with exosomes. High glucose (HG) treatment suppressed cellular proliferation, migration, and angiogenesis. Circ_0074673 knockdown enhanced the proliferation, migration, and angiogenesis of HG treated HUVECs (HG-HUVECs). As circ_0074673 and MEOX2 directly bind to miR-1200, circ_0074673 silencing promoted the biological functions of HG-HUVECs by sponging miR-1200 and further targeting MEOX2. Altogether, the loss of exosomal circ_0074673 facilitated the proliferation, migration, and angiogenesis of HG-HUVECs via the miR-1200/MEOX2 axis, suggesting that circ_0074673 is a potential therapeutic target for GDM.