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Objective To investigate the effect of resveratrol on alveolar epithelial sodium channel in acute lung injury mice and the potential mechanism.Methods Twenty-four C57BL/6 mice were randomly divided into control group, LPS group, RES group and PP242(mTORC inhibitor) group with 6 mice in each group.The pathological changes in lung tissue were evaluated by HE staining;the concentrations of total protein in bronchoalveolar lavage fluid (BALF) were assessed by BCA (bicinchoninic acid).The levels of inflammatory cytokines in BALF were determined by ELISA.The proportions of polymorphonuclear neutrophil (PMN) in BALF were detected by Flow Cytometry.The transcription levels of α-ENaC mRNA were assessed by qPCR while the protein levels of α-ENaC and p-GSK1 were measured by Western blot.Results 1)Compared with mice in control group, severe pathological lung injury changes were observed in mice of LPS group, with increased total protein levels, PMN proportions,levels of inflammatory cytokines in BALF (P<0.05), accompanied by down-regulated level of α-ENaC and p-SGK1 in lung tissues (P<0.05).2)Compared with mice in LPS group, resveratrol significantly reversed lung injury triggered by LPS, decreased total protein levels, PMN proportions, levels of inflammatory cytokines in BALF (P<0.05), with down-regulated levels of α-ENaC and p-SGK1 in lung tissues (P<0.05).3)However, PP242 prevented beneficial effects of RES on ALI.Conclusions Up-regulation of α-ENaC expression via activation of SGK1 takes part in the protective effects of RES on LPS-induced ALI in mice.
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[ ABSTRACT] AIM:To investigate the effect of adipolin/CTRP12 in LPS-induced acute respiratory distress syn-drome (ARDS) and its potential regulation on alveolar epithelial sodium channel (ENaC) in mice.METHODS:C57BL/6J mice (n=40) were randomly divided into control group, LPS group, adipolin group and wortmannin (PI3K inhibitor) group with 10 mice in each group using random number table.The pathological changes of the lung tissues were evaluated by HE staining.The alveolar fluid clearance ( AFC) was measured by Evans blue-marked albumin, and the concentrations of total protein in bronchoalveolar lavage fluid ( BALF) were assessed by bicinchoninic acid ( BCA) method.In BALF, the levels of IL-1βand TNF-αwere determined by ELISA, and the activity of myeloperoxidase ( MPO) was detected by an MPO assay kit.The total cell counts and polymorphonuclear neutrophil ( PMN) counts in the BALF were analyzed by Gi-emsa staining.The mRNA levels of α-ENaC were assessed by qPCR, while the protein levels of α-ENaC and p-Akt were determined by Western blot.RESULTS: Compared with control group, the classic ARDS pathological changes were ob-served in the mice in LPS group, manifesting by severe pathological lung injury (P 0.05), accompanied by down-regulated levels of α-ENaC and p-Akt in the lung tissues (P<0.05).The deteriorating effects triggered by LPS were significantly reversed by administration of adipolin.However, PI3K inhibitor wortmannin can-celed the beneficial effects of adipolin on LPS-induced ARDS, as evidenced by aggravated lung injury, increased levels of W/D weight ratio, protein levels, cell counts, MPO activity, and IL-1βand TNF-αlevels in the BALF (P<0.05), and decreased levels of AFC,α-ENaC and p-Akt in the lung tissues.CONCLUSION:Adipolin protects against LPS-induced ARDS in the mice by up-regulatingα-ENaC and enhancing AFC via PI3K/Akt signal pathway.
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BackgroundIn January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. MethodsIn this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020. Results267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF- and INF-{gamma}, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF- was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). ConclusionOur study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.