Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormal d-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number of Lactobacilli and a noticeable reduction in the amount of enzyme-degraded d-galactose. Replenishing chronic hypoxic rats with Lactobacillus reduced the accumulation of d-galactose and restored the deficient BMSCs. Together, our findings show that chronic hypoxia predisposes BMSCs to premature senescence, which may be due to gut dysbiosis and thus induced d-galactose accumulation.
Our study indicates that the accumulation of 4-hydroxy-2-nonenal plays an important role in lung ischemia-reperfusion injury. Alda-1 pretreatment can attenuate lung ischemia-reperfusion injury, possibly through the activation of aldehyde dehydrogenase-2, which in turn removes 4-hydroxy-2-nonenal in human pulmonary alveolar epithelial cells. Alda-1 pretreatment has clinical implications to protect lungs during cardiopulmonary bypass.
Background:The best surgical option for severe ischemic mitral regurgitation (IMR) is still controversial. The aim of this study was to perform a meta-analysis to compare the clinical outcomes of mitral valve repair (MVP) with replacement (MVR).Methods:A literature search was conducted in PubMed, Embase, and Medline using the terms “ischemic mitral regurgitation” and “repair or annuloplasty or reconstruction” and “replacement” in the title/abstract field. The primary outcomes of interest were perioperative mortality and long-term survival. Secondary outcomes were mitral regurgitation (MR) recurrence and reoperation.Results:Of 276 studies, 13 studies met the inclusion and exclusion criteria. A total of 1993 patients were included in these studies, consisting of 1259 (63%) repair cases, and 734 (37%) replacement cases. Perioperative mortality was lower with MVP compared with MVR [OR 0.61; (95% CI, 0.43–0.87; P < .05)]. There was no difference with respect to long-term survival [HR 0.75; (95% CI, 0.52–1.09; P = .14)] and reoperation [OR 0.77; (95% CI, 0.38–1.57; P = .47)]. MVP is associated with a higher recurrence of MR [OR = 4.09; (95% CI, 1.82–9.19; P < .001)].Conclusion:MVP is associated with a lower perioperative mortality but a higher recurrence of MR compared with MVR for severe IMR. No differences were found with respect to long-term survival and reoperation.
Transposition of great arteries (TGA) is a common congenital heart disease. Left ventricle (LV) is rapidly regressing and pulmonary artery banding (PAB) is utilized to retrain the undeveloped LV. Hence, it offered a unique human disease model to investigate the process of LV hypertrophy under pressure overload. Eight late referred children with TGA were enrolled. The plasma was collected at the 30 min. before and 48 hrs after PAB, and 25 proteins were identified as having significant change in proteomic analysis. Transferrin (TF) and ceruloplasmin were then confirmed. After 48 hrs incubation with TF, the size of human induced pluripotent stem cell-derived cardiomyocytes increased by two times as large as control. Meanwhile, protein synthesis and the expression of natriuretic peptide precursor A and B were significantly enhanced. TF treatment also activated both extracellular signal-regulated kinase 1/2 and activated protein kinase singling pathways. Our data provided a link to molecular components and pathways that might be involved in LV retraining. TF severed as the carrier to delivery irons, and could directly stimulate cardiomyocytes hypertrophy. TF administration may hold therapeutic potential for the biological LV retraining.
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