Data_Sheet_1_T cell immunoglobulin and mucin domain-containing protein 3 is highly expressed in patients with acute decompensated heart failure and predicts mid-term prognosis.PDF

Background and aimsT cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is mainly expressed by immune cells and plays an immunomodulatory role in cardiovascular disease. However, the prognostic value of Tim-3 in acute decompensated heart failure (ADHF) is unclear. This study aimed to investigate the expression profile of Tim-3 on CD4+ and CD8+ T cells in patients with ADHF and its impact on their prognosis.MethodsIn this prospective study, 84 patients who were hospitalized with ADHF and 83 patients without heart failure were enrolled. Main clinical data were collected during patient visits. The Tim-3 expression on CD4+ and CD8+ T cells in peripheral blood samples was assayed by flow cytometry. Long-term prognosis of the patients with ADHF was evaluated by major adverse cardiac and cerebrovascular events (MACCE) over a 12-month follow-up period.ResultsWe found that the Tim-3 expression on CD4+ T cells [2.08% (1.15–2.67%) vs. 0.88% (0.56–1.39%), p + T cells [3.81% (2.24–6.03%) vs. 1.36% (0.76–3.00%), p + and CD8+ T cells were independent risk factors of ADHF (OR: 2.76; 95% CI: 1.34–5.65, p = 0.006; OR: 2.58; 95% CI: 1.26–5.31, p = 0.010, respectively). ROC curve analysis showed that the high level of Tim-3 on CD4+ or CD8+ T cells as a biomarker has predictive performance for ADHF (AUC: 0.75; 95% CI: 0.68–0.83; AUC: 0.78, 95% CI: 0.71–0.85, respectively). During a median follow-up of 12 months, the Cox regression analysis revealed that higher Tim-3 on CD4+ and CD8+ T cells were strongly associated with increased risks of MACCE within 12 months after ADHF (HR: 2.613; 95% CI: 1.11–6.13, p = 0.027; HR: 2.762, 95% CI: 1.15–6.63, p = 0.023; respectively).ConclusionOur research indicated that the expression level of Tim-3 on CD4+ and CD8+ T cells, elevated in patients with ADHF, was an independent predictor of MACCE within 12 months after ADHF. It suggests a potential immunoregulatory role of Tim-3 signaling system in the mechanism of ADHF.</p

Additional file 1 of Sacubitril/valsartan inhibits the proliferation of vascular smooth muscle cells through notch signaling and ERK1/2 pathway

Supplementary Material

DataSheet_1_Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation.pdf

Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), Beggiatoa sp. PAC (bPAC) and Beggiatoa sp. IS2 PAC (biPAC) into macrophages by transfection to detect the effects of light-induced regulation of macrophage pro-inflammatory response and LPS-induced sepsis-induced myocardiopathy. By this method, we uncovered that blue light-induced bPAC or biPAC activation considerably inhibited the production of pro-inflammatory cytokines IL-1 and TNF-α, both at mRNA and protein levels. Further, we assembled a GelMA-Macrophages-LED system, which consists of GelMA—a type of light crosslink hydrogel, gene modulated macrophages and wireless LED device, to allow light to regulate cardiac inflammation in situ with murine models of LPS-induced sepsis. Our results showed significant inhibition of leukocytes infiltration, especially macrophages and neutrophils, suppression of pro-inflammatory cytokines release, and alleviation of sepsis-induced cardiac dysfunction. Thus, our study may represent an emerging means to treat sepsis-induced myocardiopathy and other cardiovascular diseases by photo-activated regulating macrophage function.</p

Additional file 1 of Gut microbial metabolite deoxycholic acid facilitates Th17 differentiation through modulating cholesterol biosynthesis and participates in high-fat diet-associated colonic inflammation

Additional file 1: Figure S1. Heat map depicting relative mRNA expression of cholesterol metabolism related genes in untreated and DCA-treated CD4+T cells, related to Fig. 3. Figure S2. Western-blot analysis of CYP51 protein expression upon DCA stimulation (uncropped gels), related to Fig. 3