Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia-reperfusion injury via upregulation of splenic regulatory T cells.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.

The Diagnostic Value of Mitochondrial Mass of Peripheral T Lymphocytes in Early Sepsis.

Background: Studies have shown that lymphocyte dysfunction can occur during the early stages of sepsis and that cell dysfunction is associated with mitochondrial dysfunction. Therefore, quantifying the mitochondrial function of lymphocytes in patients with sepsis could be valuable for the early diagnosis of sepsis. Methods: Seventy-nine patients hospitalized from September 2020 to September 2021 with Sepsis-3 were retrospectively analyzed and subsequently compared with those without sepsis. Results: Univariate analysis showed statistical differences between the data of the two groups regarding age, neutrophil/lymphocyte, procalcitonin (PCT), C-reactive protein, total bilirubin, serum creatinine, type B natriuretic peptide, albumin, prothrombin time, activated partial thromboplastin time, lactic acid, single-cell mitochondrial mass (SCMM)-CD3, SCMM-CD4, SCMM-CD8, and Acute Physiology and Chronic Health Evaluation II score (P < 0.05). Multivariate logistic regression analysis performed on the indicators mentioned above demonstrated a statistical difference in PCT, lactic acid, SCMM-CD4, and SCMM-CD8 levels between the two groups (P < 0.05). The receiver operating characteristic curves of five models were subsequently compared [area under the curve: 0.740 (PCT) vs. 0.933 (SCMM-CD4) vs. 0.881 (SCMM-CD8) vs. 0.961 (PCT + SCMM-CD4) vs. 0.915 (PCT+SCMM-CD8), P < 0.001]. Conclusion: SCMM-CD4 was shown to be a better diagnostic biomarker of early sepsis when compared with the traditional biomarker, PCT. Furthermore, the value of the combination of PCT and SCMM-CD4 in the diagnosis of early sepsis was better than that of SCMM-CD4 alone.

Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes.

Tanshinone IIA is a lipophilic abietane diterpene compound, which exhibits protective effects against ischaemia/reperfusion injury; however, the pathways responsible for the myocardial protective activities of tanshinone IIA remain to be elucidated. The aim of the present study was to investigate the effect of tanshinone IIA on the Janus­activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with cardiac dysfunction during ischemia/reperfusion. The results demonstrated that tanshinone IIA protected myocardial cells from hypoxia/ischemia­induced injury in vitro and recovered decreased cell viability due to activation of the JAK2/STAT3 pathway, with 10 µM tanshinone IIA exhibiting the most potent protective effects. Flow cytometric analysis revealed that tanshinone IIA reversed the apoptotic aggravation induced by JAK2/STAT3 inhibitors following hypoxic ischemia. However, JAK2 inhibitors promoted the myocardial protective effect of tanshinone IIA from hypoxic­ischemic injury. Furthermore, tanshinone IIA and JAK2/STAT3 inhibitors in combination augmented the protection of myocardial cells from apoptosis induced by ischemia/reperfusion preconditioning in vivo. In conclusion, the results of the present study indicated that JAK2/STAT3 inhibitors may enhance the protective effect of tanshinone IIA on cardiac myocytes from hypoxic ischemia-induced injury, therefore suggesting that JAK2/STAT3 inhibitors may have a potential application in combination therapies with tanshinone IIA.