Palmitic acid suppresses autophagy in neonatal rat cardiomyocytes via the cGAS-STING-IRF3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of palmitic acid (PA) on autophagy in neonatal rat cardiomyocytes (NRCMs) and explore the underlying mechanism.@*METHODS@#NRCMs were isolated and cultured for 24 h before exposure to 10% BSA and 0.1, 0.3, 0.5, or 0.7 mmol/L PA for 24 h. After the treatments, the expressions of Parkin, PINK1, p62, LC3Ⅱ/ LC3Ⅰ, cGAS, STING and p-IRF3/IRF3 were detected using Western blotting and the cell viability was assessed with CCK8 assay, based on which 0.7 mmol/L was selected as the optimal concentration in subsequent experiments. The effects of cGAS knockdown mediated by cGAS siRNA in the presence of PA on autophagy-related proteins in the NRCMs were determined using Western blotting, and the expressions of P62 and LC3 in the treated cells were examined using immunofluorescence assay.@*RESULTS@#PA at different concentrations significantly lowered the expressions of Parkin, PINK1, LC3 Ⅱ/LC3 Ⅰ and LC3 Ⅱ/LC3 Ⅰ+Ⅱ (P < 0.05), increased the expression of p62 (P < 0.05), and inhibited the viability of NRCMs (P < 0.05). Knockdown of cGAS obviously blocked the autophagy-suppressing effect of PA and improved the viability of NRCMs (P < 0.05).@*CONCLUSION@#PA inhibits autophagy by activating the cGAS-STING-IRF3 pathway to reduce the viability of NRCMs.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

A serum metabonomic study on the difference between alcohol- and HBV-induced liver cirrhosis by ultraperformance liquid chromatography coupled to mass spectrometry plus quadrupole time-of-flight mass spectrometry / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Liver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis.</p><p><b>METHODS</b>Serum specimens were collected prospectively from normal control subjects (n = 22) and patients with alcoholic cirrhosis (n = 18) or HBV-induced cirrhosis (n = 19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA).</p><p><b>RESULTS</b>Significant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered "common" biomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis.</p><p><b>CONCLUSIONS</b>There are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis. Metabonomics is a top-down systems biology tool for conducting research on clinical problems.</p>

Effect of ketamine combined with penehyclidine hydrochloride on the expression of synaptophysin in the brain of neonatal rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of ketamine combined with penehyclidine hydrochloride on the learning and memory abilities and the expression of synaptophysin in the hippocampus CA3 region in the brain of neonatal rats.</p><p><b>METHODS</b>Eighty seven-day-old Sprague-Dawly rats were randomly intraperitoneally injected with 50 mg/kg of ketamine (K group), 2 mg/kg of penehyclidine hydrochloride (P group), 50 mg/kg of ketamine plus 2 mg/kg penehyclidine hydrochloride (PK group) or normal saline (control group). The rats were trained and tested in a Morris water maze 14 days after administration. The immunhistochemical method was used to ascertain the expression of synaptophysin in the hippocampus CA3 region 24 hrs, 14 days and 28 days after administration.</p><p><b>RESULTS</b>In the Morris water maze training, the rats in the PK group performed worst, followed by the K group. The rats from the P and NS groups performed well. Compared with the NS group, the expression of synaptophysin in the K and the PK groups decreased significantly 24 hrs and 14 days after administration (p<0.05). The PK group had lower synaptophysin expression than the K group 24 hrs and 14 days after administration (p<0.05). Up to 28 days after administration, the synaptophysin expression increased in all of the four groups and there were no significant differences between groups.</p><p><b>CONCLUSIONS</b>Ketamine combined with penehyclidine hydrochloride may inhibit more significantly learning and memory abilities and the synaptophysin expression in the hippocampus CA3 region than ketamine alone in neonatal rats. Penehyclidine hydrochloride alone has no effect on learning and memory abilities and the synaptophysin expression. The synaptophysin expression may increase to a normal level by training and with increasing age.</p>