Introduction: The present investigation determined the protective effect of myricitrin against sepsis-associated encephalopathy in rats. Material and methods: Sepsis was induced by cecal ligation and puncture (CLP); rats were treated with 30 or 100 mg/kg of myricitrin for 5 days prior to the induction of CLP. The effect of myricitrin was observed by determining the neurological function using the open field test and step-down inhibitory avoidance test. Cerebral oedema and the levels of inflammatory and oxidative stress mediators were determined in brain tissues. Moreover, the expression levels of Bcl-2, Bax, IκB-α, nuclear factor κB (NF-κB), caspase-3 and NLRP3 were estimated in brain tissues by Western blotting and the mRNA expression of NF-κB, caspase-3 and NLRP3 in brain tissues was estimated by realtime polymerase chain reaction. An immunofluorescence assay was performed to estimate inflammasome activity. Results: The results suggest that treatment with myricitrin protects neuronal function in rats with CLP-induced sepsis. Decreases in inflammation and oxidative stress mediators were observed in the brain tissues of the myricitrin-treated group compared to the CLP group. Moreover, treatment with myricitrin ameliorated the altered Bcl-2, Bax, IκB-α, NF-κB, caspase-3 and NLRP3 protein and mRNA expression levels in the brain tissues of septic rats. Conclusions: The data reveal that myricitrin ameliorated neuroinflammation and improved memory in rats with CLP-induced sepsis by regulating the NLRP3/Bax/Bcl signalling pathway.
Circular RNA (circRNA) has been confirmed to be involved in regulating sepsis‐induced acute kidney injury (AKI). Our research aims to explore circ‐ZNF644 role in the development of sepsis‐induced AKI. Lipopolysaccharide (LPS) was used to induce kidney tubular epithelial cell (HK2) injury. ELISA assay was performed to measure the concentrations of inflammation factors. Cell functions were determined by cell counting kit 8 assay, EdU assay and flow cytometry. Protein expression was evaluated by Western blot analysis. Quantitative real‐time PCR was used to detect relative expression of circ‐ZNF644, miR‐335‐5p and homeodomain‐interacting protein kinase 1 (HIPK1). RNA interaction was confirmed by dual‐luciferase reporter assay and RIP assay. LPS enhanced HK2 cell inflammation, oxidative stress, apoptosis, and reduced proliferation. Circ‐ZNF644 was overexpressed in sepsis‐induced AKI patients. Circ‐ZNF644 knockdown suppressed LPS‐induced HK2 cell injury, and this effect could be revoked by miR‐335‐5p inhibitor. MiR‐335‐5p was sponged by circ‐ZNF644, and its expression was downregulated in sepsis‐induced AKI patients. HIPK1 was targeted by miR‐335‐5p, and its expression could be suppressed by circ‐ZNF644 knockdown. MiR‐335‐5p had an inhibition effect on HK2 cell injury induced by LPS, and HIPK1 overexpression could reverse this effect. Circ‐ZNF644 knockdown relieved LPS‐induced HK2 cell injury through the miR‐335‐5p/HIPK1 axis, confirming that circ‐ZNF644 contributed to sepsis‐induced AKI.
Background: Emerging evidence has indicated that interleukin-8 (IL-8) gene-251A/T polymorphism may affect individual susceptibility to sepsis. However, the results of published studies are inconclusive. The aim of this meta-analysis was to elucidate the association between this polymorphism and the risk and mortality of sepsis. Methods: Relevant publications were searched from PubMed, EmBase, and Web of Science databases up to January 31, 2021, with studies only in English. The reference lists of the retrieved studies were investigated as well. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to figure out the relationship between IL-8-251 A/T polymorphisms and the risk and mortality of sepsis. All of the data were analyzed with Stata 16.0. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: This meta-analysis will summarize the relationship between IL-8-251 A/T polymorphism and the risk and mortality of sepsis.
Background: The present study sought to investigate the regulatory role of the long non-coding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) in a mouse model of acute lung injury (ALI) and in primary mouse pulmonary microvascular endothelial cells (MPVECs) treated with lipopolysaccharide (LPS).Methods: C57BL/6 mice were given adenovirus (Ad) sh-CHRF or negative control (NC) before undergoing cecal ligation and perforation. MPVECs transfected with Adsh-CHRF or NC were treated with LPS. Double luciferase assay was used to detect the binding of miR-146a to CHRF or Notch1. Subsequently, MPVECs were co-transfected with miR-146a inhibitor and sh-CHRF for 24 hours, and then treated with LPS.Results: High expression of CHRF was detected in septic mice. Cecal ligation and perforation induced ALI and apoptosis in mice, whereas, CHRF knockout could inhibit ALI. The protein expression levels of TNF-α, IL-1β and IL-6 in the lung and bronchoalveolar lavage fluid of the CLP group were up-regulated, whereas the expression of IL-4 and IL-10 was down-regulated. CHRF inhibition reduced the production of proinflammatory cytokines in septic mice. The inhibitory effect of CHRF gene knockdown on lung inflammation and apoptosis was confirmed in the septic cell model. Mechanistic investigation showed that CHRF up-regulated the level of Notch1 by sponging miR-146a. Additionally, the low expression of miR-146a reversed the inhibitory effect of CHRF gene knockout on LPS-induced inflammatory response and apoptosis. Together, in vivo and in vitro results demonstrated that CHRF enhanced sepsis-induced ALI by targeting miR-146a and up-regulating Notch1.Conclusions: CHRF can induce inflammation and apoptosis caused by sepsis by miR-146a/Notch1 axis. Therefore, it may serve as a potential drug target for treating sepsis-induced ALI.
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