ObjectiveTo evaluate the association between serum galectin-3 and all-cause death (ACD) and cardiovascular death (CVD) in patients with chronic heart failure (CHF).MethodsThe PubMed and Embase databases and Clinical Trials Registry (www.clinicaltrials.gov) were searched for studies with data on serum galectin-3 and ACD and CVD in CHF patients. The hazard ratios (HRs) of ACD and CVD were calculated and presented with 95% CIs. HRs were pooled using fixed effects or random effects models when appropriate. Sensitivity analysis, meta-regression and subgroup analysis were applied to find the origin of heterogeneity. Visual inspection of Begg's funnel plot and Egger's test were performed to assess the possibility publication bias.ResultsPooled data included the results from 6,440 patients from 12 studies in the meta-analysis. Higher serum galectin-3 was associated with a higher risk of ACD (HR, 1.38; 95% CI, 1.14–1.67) and CVD (HR, 1.13; 95% CI, 1.02–1.25) in CHF patients. In the subgroup analyses, higher serum galectin-3 was associated with an increased risk of ACD in all subgroups. The pooled HR of the shorter follow-up group (1.78; 95% CI, 1.50–2.11) was significantly higher than the pooled HR of the longer follow-up group (1.15; 95% CI, 1.05–1.25). Sensitivity analysis of eliminating one study in each turn indicated that Koukoui et al.'s study had the largest influence on the risk of all-cause death. All-cause death publication bias was not detected (Pr>|z| = 0.35 for Begg's test and P>|t| = 0.15 for Egger's test).ConclusionsSerum galectin-3 has prognostic value of both all-cause death and cardiovascular death in CHF. Serum galectin-3 could be useful for risk classification in patients with CHF.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=193399.

Calcific aortic valve disease (CAVD) is a valvular disease frequently in the elderly individuals that can lead to the valve dysfunction. Osteoblastic differentiation of human aortic valve interstitial cells (HAVICs) induced by inflammation play a crucial role in CAVD pathophysiological processes. To date, no effective drugs for CAVD have been established, and new agents are urgently needed. Piericidin glycosides, obtained from a marine-derived Streptomyces strain, were revealed to have regulatory effects on mitochondria in previous studies. Here, we discovered that 13-hydroxypiericidin A 10-O-α-D-glucose (1→6)-β-D-glucoside (S18), a specific piericidin diglycoside, suppresses lipopolysaccharide- (LPS) induced inflammatory responses of HAVICs by alleviating mitochondrial stress in an interleukin (IL)-37-dependent manner. Knockdown of IL-37 by siRNA not only exaggerated LPS-induced HAVIC inflammation and mitochondrial stress but also abrogated the anti-inflammatory effect of S18 on HAVICs. Moreover, S18 alleviated aortic valve lesions in IL-37 transgenic mice of CAVD model. Microscale thermophoresis (MST) and docking analysis of five piericidin analogues suggested that diglycosides, but not monoglycosides, exert obvious IL-37-binding activity. These results indicate that S18 directly binds to IL-37 to alleviate inflammatory responses in HAVICs and aortic valve lesions in mice. Piericidin diglycoside S18 is a potential therapeutic agent to prevent the development of CAVD.