hPMSCs prevent erythrocytes dysfunction caused by graft versus host disease via promoting GSH synthesis.

Background: Oxidative stress is increased in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients and leads to the development of graft versus host disease (GVHD). Mesenchymal stromal cells (MSCs) can ameliorate GVHD by regulating the function of T cells. However, whether MSCs can modulate erythrocyte antioxidant metabolism and thus reduce GVHD is not known.

Human placental mesenchymal stromal cells promote the formation of CD8CD122PD-1Tregs via CD73/Foxo1 to alleviate liver injury in graft-versus-host disease mice.

Background: Human placental mesenchymal stromal cells (hPMSCs) are known to limit graft-versus-host disease (GVHD). CD8CD122PD-1Tregs have been shown to improve the survival of GVHD mice. However, the regulatory roles of hPMSCs in this subgroup remain unclear.

hPMSCs Regulate the Level of TNF-α and IL-10 in Th1 Cells and Improve Hepatic Injury in a GVHD Mouse Model via CD73/ADO/Fyn/Nrf2 Axis.

Mesenchymal stem cells (MSCs) ameliorate graft-versus-host disease (GVHD)-induced tissue damage by exerting immunosuppressive effects. However, the related mechanism remains unclear. Here, we explored the therapeutic effect and mechanism of action of human placental-derived MSCs (hPMSCs) on GVHD-induced mouse liver tissue damage, which shows association with inflammatory responses, fibrosis accompanied by hepatocyte tight junction protein loss, the upregulation of Bax, and the downregulation of Bcl-2.

Human placental mesenchymal stromal cells modulate IFN-γ and IL-10 secretion by CD4T cells via CD73, and alleviate intestinal damage in mice with graft-versus-host disease.

Background: Intestinal inflammatory damage is an important factor in the development of graft-versus-host disease (GVHD). IFN-γ and IL-10 play key roles in gastrointestinal inflammation, and human placental mesenchymal stromal cells (hPMSCs) can alleviate inflammatory damage during GVHD. CD73 is highly expressed by hPMSCs.

Protective effect of hydroxysafflor yellow A on renal ischemia‑-reperfusion injury by targeting the Akt‑Nrf2 axis in mice.

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Hydroxysafflor yellow A (HSYA), a natural compound isolated from , has been found to possess anti-inflammatory and antioxidant properties. However, the protective effects and potential mechanism of HSYA on I/R-induced AKI remains unclear.

hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4 T Cells by Targeting the PTEN/PI3K-Nrf2 Axis.

Mesenchymal stem cells (MSCs)-derived exosomes were considered a novel therapeutic approach in many aging-related diseases. This study aimed to clarify the protective effects of human placenta MSCs-derived exosomes (hPMSC-Exo) in aging-related CD4 T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model. Senescent T cells were detected SA-β-gal stain.

Cosmc transfection decreases malignant behavior of Tn cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.

Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression. In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased. Core 1-, 2-, and 3-derived O-glycans were absent in Tn cells.

hPMSCs inhibit the expression of PD-1 in CD4IL-10 T cells and mitigate liver damage in a GVHD mouse model by regulating the crosstalk between Nrf2 and NF-κB signaling pathway.

Background: The activation of T cells and imbalanced redox metabolism enhances the development of graft-versus-host disease (GVHD). Human placenta-derived mesenchymal stromal cells (hPMSCs) can improve GVHD through regulating T cell responses. However, whether hPMSCs balance the redox metabolism of CD4IL-10 T cells and liver tissue and alleviate GVHD remains unclear.

hPMSCs protects against D-galactose-induced oxidative damage of CD4 T cells through activating Akt-mediated Nrf2 antioxidant signaling.

Background: Mesenchymal stem cells (MSCs) were considered a regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4 T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4 T cell senescence and identified the underlying mechanisms using a D-gal-induced mouse aging model.

Downregulated Recycling Process but Not De Novo Synthesis of Glutathione Limits Antioxidant Capacity of Erythrocytes in Hypoxia.

Red blood cells (RBCs) are susceptible to sustained free radical damage during circulation, while the changes of antioxidant capacity and regulatory mechanism of RBCs under different oxygen gradients remain unclear. Here, we investigated the changes of oxidative damage and antioxidant capacity of RBCs in different oxygen gradients and identified the underlying mechanisms using an in vitro model of the hypoxanthine/xanthine oxidase (HX/XO) system. In the present study, we reported that the hypoxic RBCs showed much higher oxidative stress injury and lower antioxidant capacity compared with normoxic RBCs.

Oligosaccharide attenuates aging-related liver dysfunction by activating Nrf2 antioxidant signaling.

Chitosan oligosaccharide (COS) is the depolymerized product of chitosan possessing various biological activities and protective effects against inflammation and oxidative injury. The aim of the present study was to investigate the antioxidant effects of COS supplements on aging-related liver dysfunction. We found that COS treatment significantly attenuated elevated liver function biomarkers and oxidative stress biomarkers and decreased antioxidative enzyme activities in liver tissues in D-galactose (D-gal)-treated mice.

IL-1β enhances human placenta-derived mesenchymal stromal cells ability to mediate Th1/Th2 and Th1/CD4IL-10 T cell balance and regulates its adhesion, proliferation and migration via PD-L1.

Human placenta-derived mesenchymal stromal cells (hPMSCs) are promising candidates for the treatment of graft-versus-host disease (GVHD), which is associated with high IL-1β levels. In this study, the effects of IL-1β and hPMSCs on each other were investigated by analyzing the proportion of Th1, Th2 and CD4IL-10 T cells and PD-L1 expression, as well as the adhesion, migration, and proliferation of hPMSCs. The results showed that hPMSCs decreased IL-1β levels and downregulated Th1/Th2 and Th1/CD4IL-10 T cells ratios in the GVHD model.

Human placenta derived mesenchymal stromal cells alleviate GVHD by promoting the generation of GSH and GST in PD-1T cells.

Aims: To investigate whether placenta-derived mesenchymal stromal cells (hPMSCs) have immunoregulatory effects on PD-1 T cell generation by controlling ROS production and thus alleviating GVHD.

Main Methods: Flow cytometry was used to analyze the percentage of PD-1 T cells, as well as the generation of ROS, GSH and GST in PD-1 T cells. The expression of GST in the spleen and liver was analyzed by western blotting.

Mouse trefoil factor 3 ameliorated high-fat-diet-induced hepatic steatosis via increasing peroxisome proliferator-activated receptor-α-mediated fatty acid oxidation.

Hepatic trefoil factor 3 (Tff3) was identified as a potential protein for the treatment of diabetes, yet the effect of Tff3 on nonalcoholic fatty liver disease (NAFLD) has never been explored. Here, we found that the expression of hepatic Tff3 was significantly decreased in NAFLD mice models, suggesting that Tff3 was a potential marker gene for NAFLD. Restoring the expression of Tff3 in the liver of NAFLD mice, including diabetic (db), obese (ob/ob), and diet-induced obese mice, with adenovirus-mediated Tff3 () apparently attenuates the fatty liver phenotype.

IL-27 Promotes Human Placenta-Derived Mesenchymal Stromal Cell Ability To Induce the Generation of CD4IL-10IFN-γ T Cells via the JAK/STAT Pathway in the Treatment of Experimental Graft-versus-Host Disease.

Human mesenchymal stromal cells (MSCs) harbor immunomodulatory properties to induce the generation of suppressive T cells. MSCs have been successfully used in treating graft-versus-host disease (GVHD) accompanied by abundant inflammatory cytokines such as IL-27. This study investigated the effects of IL-27 on the human placenta-derived MSCs (hPMSCs) to induce generation of CD4IL-10IFN-γ T cells in vitro and in the humanized xenogenic GVHD NOD/SCID model.

Inhibition of Glutathione Synthesis via Decreased Glucose Metabolism in Stored RBCs.

Background/aims: Although red blood cells (RBCs) transfusions can be lifesaving, they are not without risk. RBCs storage is associated with the abnormal metabolism of glutathione (GSH), which may increase the risk of the oxidative damage of RBCs after transfusion. The responsible mechanisms remain unknown.

Human placenta-derived mesenchymal stem cells ameliorate GVHD by modulating Th17/Tr1 balance via expression of PD-L2.

Aims: To examine whether human placenta mesenchymal stem/stromal cells (hpMSCs) mitigate graft-versus-host-disease (GVHD) via regulation of Th17 and Tr1.

Materials And Methods: hpMSCs or phosphate buffered saline (PBS, as a control) were injected into humanized xeno-GVHD NOD/SCID mouse model. Effects on body weights and survival times were determined.

hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway.

Background: Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation.

Involvement of soluble B7-H3 in combination with the serum inflammatory cytokines interleukin-17, -8 and -6 in the diagnosis of hepatocellular carcinoma.

Previous studies have demonstrated that B7-H3, and the inflammatory cytokines interleukin (IL)-17, IL-8 and IL-6, are involved in the development of a variety of tumors. The objectives of the present study were: i) To investigate the association between soluble B7-H3 (sB7-H3) and cytokine levels of IL-17, IL-8 and IL-6 in the serum of patients with hepatocellular carcinoma (HCC); and ii) to determine their potential value for use in HCC diagnosis. Serum sB7-H3, IL-17, IL-8 and IL-6 levels in the HCC patients and healthy control subjects were measured using ELISA.

Involvement of the JAK-STAT pathway in collagen regulation of decidual NK cells.

Problem: The mechanisms underlying the regulation of decidual natural killer cells (dNKs) at the maternal-fetal interface are unclear.

Method Of Study: Primary trophoblasts (TROs), decidual stromal cells (DSCs), and dNKs were cocultured, and responses to LAIR-2 (LAIR-1 inhibitor) and P4H shRNA (collagen inhibitor) were studied.

Results: Coculture of dNKs with primary TROs/DSCs resulted in downregulation of Th1 cytokine production by dNKs.

Restoring Ovarian Function With Human Placenta-Derived Mesenchymal Stem Cells in Autoimmune-Induced Premature Ovarian Failure Mice Mediated by Treg Cells and Associated Cytokines.

Regulatory T (Treg) cells play a key role in the regulation of autoimmunity and transplantation. Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has a potential to restore ovarian dysfunction associated with premature ovarian failure (POF), while the exact function of the Treg cells in the transplantation still needs to be further investigated. In this study, hPMSCs were intravenously injected into POF mice following zona pellucida glycoprotein 3 (pZP3) treatment.