ABSTRACT
BACKGROUND AND AIMS: The exosomal long noncoding RNAs (lncRNAs) have been reported to have cardioprotective effects on ischemia-reperfusion (I/R) injury by hindering ferroptosis, but the role of lncRNA Mir9-3 host gene (Mir9-3hg) in cardiac I/R injury remains unclear. METHODS AND RESULTS: Exosomes were extracted from mouse bone marrow mesenchymal stem cells (BMSCs) and identified by detecting the exosome specific marker levels, and the results showed that Mir9-3hg was highly expressed in BMSCs-Exo. Hypoxia/reoxygenation (H/R)-treated HL-1 mouse cardiomyocytes were incubated with exosomes extracted from BMSCs transfected with Mir9-3hg siRNA. BMSCs-Exo incubation observably facilitated cell proliferation, increased glutathione (GSH) content, and reduced iron ion concentration, reactive oxygen species (ROS) level and ferroptosis marker protein levels in H/R-treated cells, while interfering Mir9-3hg reversed these effects. RNA binding protein immunoprecipitation assay was found that Mir9-3hg bound with pumilio RNA binding family member 2 (Pum2) protein and downregulated Pum2 expression. Silence of Pum2 reversed the effects of Mir9-3hg inhibition on cell functions. Chromatin immunoprecipitation assay was revealed that Pum2 bound with peroxiredoxin 6 (PRDX6) promoter and restrained PRDX6 expression. Silence of PRDX6 reversed the improved effects of Pum2 downregulation on cell functions. Additionally, BMSCs-Exo treatment ameliorated cardiac function in I/R-treated mice by inhibiting cardiomyocyte ferroptosis. CONCLUSIONS: BMSCs-Exo treatment attenuates I/R-induced cardiac injury by inhibiting cardiomyocyte ferroptosis through modulating the Pum2/PRDX6 axis, thereby ameliorating cardiac function.
Subject(s)
Ferroptosis , Myocytes, Cardiac , RNA, Long Noncoding , Reperfusion Injury , Animals , Mesenchymal Stem Cells , Mice , Myocytes, Cardiac/cytology , Peroxiredoxin VI/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolismABSTRACT
OBJECTIVE: To explore the risk factors of portal vein thrombosis (PVT) after splenectomy and esophagogastric devascularization for advanced schistosomiasis portal hypertension. METHODS: The clinical data were collected retrospectively from 211 advanced schistosomiasis portal hypertension patients after splenectomy and esophagogastric devascularization from August, 2004 to March 2014, and all the data were analyzed statistically for the risk factors of PVT after the surgery by single factor analysis and Logistic regression analysis. RESULTS: Totally 59 patients were found with PVT and the incidence was 27.96% (59/211). The single factor analysis showed that 8 factors were related to PVT after surgery, including the history of upper gastrointestinal hemorrhage, the diameter of portal vein, the diameter of splenic vein, esophageal varices, ascites, portal hypertension gastropathy, gastric varices , and blood ammonia level. The Logistic regression analysis showed that the independent risk factors of PVT were broadening of the diameter of portal vein (OR = 1.763 , P = 0.000) and portal hypertension gastropathy (OR = 1.089, P = 0.037). CONCLUSIONS: The incidence of PVT after surgery for advanced schistosomiasis is high, and the independent risk factors are broadening of diameter of portal vein and portal hypertension gastropathy.
Subject(s)
Hypertension, Portal/surgery , Portal Vein , Postoperative Complications/etiology , Schistosomiasis/complications , Splenectomy/adverse effects , Venous Thrombosis/etiology , Adult , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
The poor survival and differentiation of the donor cells in the infarcted myocardium has hampered the therapeutic efficacy of cell transplantation. A self-assembling polypeptide RAD16-II (Ac-RARADADARARADADA-CONH2) spontaneously assembles into stable nanofiber scaffolds, which mimic natural extracellular matrix at 0.1-1% peptide concentrations in the myocardium. We isolated mesenchymal stem cells from the bone marrow of adult male rats that express both c-kit and Nkx2.5, a cardiac transcription factor, yielding selected mesenchymal stem cells (SMSCs). We initially confirmed that the self-assembling polypeptide scaffolds are conducive to growth, survival and differentiation of SMSCs in vitro. Subsequently, SMSCs mixed with the self-assembling polypeptide were injected into the infarcted area at 30 min after the establishment of myocardial infarction in female rats. The donor cells were tracked with Y chromosome in the myocardium. The changes of cardiac function, myocardial structure and capillary density were detected at 4 weeks after cell transplantation. The hearts transplanted with SMSCs incorporated into the nanofiber scaffolds showed smaller infarction size (19.55 ± 2.1%) than the hearts injected with SMSCs (27.37 ± 4.8%). Importantly, the systolic function indices, left ventricle ejection fraction and left ventricle fractional shortening, were significantly improved in the animals transplanted with SMSCs mixed with the nanofiber scaffolds (59.31 ± 4.9% and 31.91 ± 8.1%), compared to those with SMSCs alone (48.31 ± 9.2% and 23.58 ± 8.5%). In conclusion, transplantation of SMSCs mixed with the self-assembling polypeptide RAD16-II is more effective to promote myocardial regeneration and attenuate cardiac injury in a rat model of myocardial infarction.