ABSTRACT
BACKGROUND: Sepsis is perceived as lethal tissue damage and significantly increases mortality in combination with acute kidney injury (AKI). M2 macrophages play important roles in the secretion of anti-inflammatory and tissue repair mediators. We aimed to study the role of Dehydroandrographolide (Deh) in sepsis-associated AKI in vitro and in vivo through lipopolysaccharide (LPS)-induced macrophages model and cecal ligation and puncture-induced AKI mice model, and to reveal the mechanism related to M2 macrophage polarization. METHODS: Enzyme-linked immunosorbent assay kits were used to assess the levels of inflammatory factors. Expression of markers related to M1 macrophages and M2 macrophages were analyzed. Additionally, dual specificity phosphatase 3 (DUSP3) expression was tested. Cell apoptosis was evaluated by flow cytometry analysis and terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Moreover, renal histological assessment was performed by using hematoxylin and eosin staining. RESULTS: Deh reduced inflammation of THP-1-derived macrophages exposed to LPS. Besides, Deh induced the polarization of M1 macrophages to M2 and downregulated DUSP3 expression in THP-1-derived macrophages under LPS conditions. Further, DUSP3 overexpression reversed the impacts of Deh on the inflammation and M2 macrophages polarization of THP-1-derived macrophages stimulated by LPS. Additionally, human proximal tubular epithelial cells (HK-2) in the condition medium from DUSP3-overexpressed THP-1-derived macrophages treated with LPS and Deh displayed decreased viability and increased apoptosis and inflammation. The in vivo results suggested that Deh improved the renal function, ameliorated pathological injury, induced the polarization of M1 macrophages to M2, suppressed inflammation and apoptosis, and downregulated DUSP3 expression in sepsis-induced mice. CONCLUSION: Deh facilitated M2 macrophage polarization by downregulating DUSP3 to inhibit septic AKI.
Subject(s)
Acute Kidney Injury , Diterpenes , Sepsis , Humans , Mice , Animals , Dual Specificity Phosphatase 3/metabolism , Lipopolysaccharides/toxicity , Macrophages/metabolism , Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Sepsis/complications , Sepsis/drug therapyABSTRACT
OBJECTIVE: To explore the prevalence of acute gastroenteritis (AGE) and associated factors in children and adolescents in the USA from 1999 to 2018 using nationally representative data. DESIGN: A retrospective cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (NHANES) database. PARTICIPANTS: 25 361 children and adolescents aged 6-17 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: Whether the patient suffered from AGE. RESULTS: Totally 1882 suffered from AGE. The overall monthly prevalence of AGE in children and adolescents was 7.69%. From 1999 to 2018, the prevalence of AGE in the USA had been decreasing over time. The decreasing trend was observed in all subgroups, including age, gender, body mass index (BMI), education level, poverty index and eating food at the restaurant. There were two small upticks from 2003 to 2007 and 2013 to 2015. AGE was negatively associated with male compared with female (OR=0.86, 95% CI: 0.73 to 0.99, p=0.035), Mexican American (OR=0.82, 95% CI: 0.70 to 0.97, p=0.018) and non-Hispanic Black (OR=0.80, 95% CI: 0.69 to 0.93, p=0.003) compared with non-Hispanic White. AGE was positively associated with obesity compared with underweight and normal weight (OR=1.37, 95% CI: 1.15 to 1.62, p<0.001). CONCLUSION: The monthly prevalence of AGE was 7.69% and showed a downward trend from 1999 to 2018 in the USA.
