Background: Pulmonary fibrosis (PF) is a fatal disease with increasing incidence. Ligustilide (LIG) has been shown to inhibit oxidative stress, apoptosis, and inflammation. Here we investigated the possible effect of LIG on bleomycin-induced PF in Sprague-Dawley rats.Methods: PF rats were set up through a single endotracheal injection of bleomycin (5 mg/kg). Then rats were treated with 20, 40, and 80 mg/kg LIG for four weeks, and the effects were estimated.Results: Overall, LIG significantly improved ventilation and reduced hyperplasia, and treatment of LIG reduced fibrosis as indicated by Masson staining and reduced expression of transforming growth factorbeta (TGF-β), Fibronectin, and alpha-smooth muscle actin (α-SMA). Oxidative stress was induced with bleomycin while inhibited with LIG, as showed with rebalanced serum lactate dehydrogenase (LDH), and tissue superoxide dismutase (SOD), glutathione peroxidase (GSH) and malondialdehyde (MDA). Apoptosis was further inhibited with LIG, as shown with Terminal dUTP nick-end labeling (TUNEL) staining and expression of Caspase-3, Caspase-9, Bax, and Bcl-2. Th1/Th2 balance was also rebuilt as evaluated with CD4 and IFNγ/IL-4 labeled flow cytometry of peripheral blood mononuclear cells (PBMCs) and expression of inducible nitric oxide synthase (iNOS) and IL-10 in the serum and lung. Protein expression of Toll-like receptor 4 (TLR4), HSP60-TLR4-myeloid differentiation factor 88 (Myd88) and nuclear factor-kappa B (NF-κB) p-P65/P65 was significantly reduced with LIG treatment. All the effects of LIG exhibited in a dosedependent way.Conclusions: LIG improved bleomycin-induced PF with improved ventilation, reduced fibroblast, reduced oxidative stress and apoptosis, and rebalanced Th1/Th2 immunity, through TLR4/MyD88/NF-κB P65 signaling.

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.

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