Astragalus polysaccharide (APS) has been widely reported to play an important role in inflammatory response. In this study, we aimed to explore the effects and underlying mechanisms of APS on lipopolysaccharide (LPS)-induced inflammation injury in H9c2 cardiomyoblasts. H9c2 cells were treated with different concentrations of APS, and cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay. Then, the effect of APS on cell viability and apoptosis induced by LPS was determined by CCK-8, flow cytometry, and western blot. The expression and release of inflammatory cytokines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, expression of miR-127 in H9c2 cells was analyzed by qRT-PCR, and knocked down by transfection with miR-127 inhibitor. Western blot was used to analyze signaling pathway molecules. APS had no effect on H9c2 cells viability. However, APS could alleviate LPS-induced inflammation injury by increasing cell viability, reducing apoptosis, and inhibiting release of inflammatory cytokines in H9c2 cells (P < 0.05). Additionally, we found that APS increased toll-like receptor 4 (TLR4) expressions in LPS-treated H9c2 cells. Mechanistically, we found that APS exerted the protective effect by down-regulating LPS-increased expression of miR-127 (P < 0.05), inhibiting nuclear factor kappa B (NF-κB), JNK and promoting phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways in LPS-treated H9c2 cells. The results demonstrated that APS could protect H9c2 cells against LPS-induced inflammation injury, which might be partially due to miR-127 down-regulation and regulation of NF-κB, JNK, and PI3K/AKT signaling pathways. These findings indicated that APS might be a potential therapeutic drug for treatment of myocarditis.

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Background: Cardiomyocytes loss is the predominant pathogenic characteristic in the hypoxia-induced injury. Meanwhile, it has been corroborated that Bcl-2 E1B 19-KDa interacting protein 3 (BNIP3) provokes apoptosis and autophagy. For moderating cardiomyocytes loss, we initially probed the cyto-protection effects of 6-Gingerol (6 G), meanwhile, its potential mechanisms associated with BNIP3 were elucidated in our studies. Methods: We pretreated cardiomyocytes H9c2 cells with 6 G at different concentrations (0-100 lM) before exposure to hypoxia. Thereafter, the cell viability, lactate dehydrogenase (LDH), apoptosis and protein expression were respectively assessed using cell counting kit-8 and methyl thiazolyl tetrazolium (MTT) assay, LDH assay kit, Annexin V-fluorescein isothiocyannate/propidium iodide (Annexin V-FITC/PI) apoptosis detection kit and Western blotting analysis. In addition, we also analyzed BNIP3 level after treatment. Moreover, we enforced the exogenous overexpression of BNIP3 and then evaluated the cell viability, apoptosis, and protein level again. Results: In our present work, we observed that the cell viability was promoted by 6 G in the hypoxiainduced H9c2 cells in a dose-dependent manner. Moreover, hypoxia-induced LDH release, apoptosis and autophagy were inhibited by 6 G pretreatment through promoting phosphorylation of PI3K, AKT and mTOR. Remarkably, accumulation of BNIP3 protein was significantly reduced by 6 G in hypoxia-induced H9c2 cells. Mechanistically, 6 G initiated the phosphorylated expression of PI3K, AKT and mTOR by down-regulating BNIP3 with reducing cardiomyocytes apoptosis and autophagy. Conclusion: Hypoxia-induced cardiomyocytes injury was ameliorated by 6 G through suppressing BNIP3 expression with triggering PI3K/AKT/mTOR signalling pathway.

IL-36α exerts proinflammatory effects in Aspergillus fumigatus keratitis of mice through the pathway of IL-36α/IL-36R/NF-κB.

Background:Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients.Methods:A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg−1·day−1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o’clock, 11 to 13 o’clock, and 17 to 19 o’clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups.Results:There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3–10.3] vs. 10.7 [9.1–12.1] mmol/L, Z = −2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1–63.7]% vs. 11.8 [3.0–36.7]%, Z = −2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050).Conclusions:In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients.Trial RegistrationClinicalTrials.gov, NCT03439618; https://clinicaltrials.gov/ct2/show/record/NCT03439618