Objective To explore the effects and mechanisms of deoxycholic acid(DCA)on oxidative stress in human BAR-T cells.Methods The human Barrett epithelial cell line BAR-T was cultured in vitro,and the BAR-T cells were intervened with different concentrations of DCA(100,200,and 300 μmol/L)and different action time(30 min,60 min,3 h and 6 h).The mRNA and protein expression of COX-2 were detected by Real-time PCR and Western blotting assay.The intracellular reactive oxygen species(ROS)content was detected by direct microscope observation and flow cytometry,and was compared with that of 200 μmol/L DCA+5 mmol/L NAC(ROS scavenger N-acetylcysteine)group;cellular immunofluorescence was used to detect the entry of cellular p65 protein into the nucleus,which was then compared with 200 μmol/L DCA+PDTC(100 μmol/L,NF-κB pathway inhibitor)group.Results Compared to the control group,DCA increased ROS content in BAR-T cells in a dose-dependent manner.Additionally,5 mmol/L NAC significantly inhibited DCA-induced ROS release.Furthermore,both 200 μmol/L and 300 μmol/L DCA significantly increased COX-2 mRNA expression compared to the control group at the same intervention time.The 6 h groups for both 200 μmol/L and 300 μmol/L DCA showed a significant increase in COX-2 mRNA expression compared to the 1 h group.Compared to the control group,treatment with 200 μmol/L DCA significantly increased the expression of COX-2 protein.Meanwhile,200 μmol/L DCA promoted the nucleation of p65 protein,which was inhibited by PDTC.Conclusion DCA activates the NF-κB signaling pathway and upregulates the expression of COX-2 by elevating the intracellular ROS expression and promoting the entry of p65 protein into the nucleus.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

Objective: To study the effect of berberine (BR) on ventricular remodeling in experimental rats with myocardial infarction (MI) and its mechanisms.
Methods: The MI model of experimental rats was established by ligation of the left anterior descending coronary artery and the MI animals were randomly divided into 3 groups: MI+BR group, in which the rats received BR 20 mg/kg.d, Sham group and MI group, the rats in those 2 groups received the same volume of normal saline. All animals were treated for 8 weeks. The cardiac function and structure were assessed by echocardiography, cardiac interstitial collagen deposition was evaluated by Masson stain, the myocardial cell apoptosis was detected by Tunel method, and the activation of nuclear factor (NF-κB) was also examined.
Results: For echocardiography, MI group had enlarged left ventricular end diastolic diameter (7.28 ± 0.29) mm than Sham group (6.86 ± 0.36) mm,P<0.05, but it decreased in MI+BR group (6.89 ± 0.99) mm,P>0.05. MI group had increased left ventricular end systolic diameter (5.88 ± 0.33) mm than Sham group (4.61 ± 0.31) mm, but it decreased in MI+BR group (4.68 ± 1.17) mm, allP< 0.01. MI group showed increased left ventricular posterior wall compensatory hypertrophy (1.81 ± 0.85) mm than Sham group (1.67 ± 0.16 mm),P<0.05, while in MI+BR group, it was deereased to (1.65 ± 0.14) mm. MI group presented decreased LVEF (45.77 ± 3.17) % than Sham group (67.28 ± 4.15) %, but it increased in MI+BR group (64.64 ± 5.82) %, allP<0.01. For Masson stain, cardiac interstitial collagen deposition in MI group (11.39 ± 0.45) % was higher than Sham group (2.65 ± 0.45) %, but less in MI+BR group (7.00 ± 0.87) %, allP<0.01. For Tunel examination, the myocardial cell apoptosis index was increased in MI group (21.31 ± 2.34) than Sham group (0.99 ± 0.38), but decreased in MI+BR group (14.15 ± 1.62), allP<0.01. For NF-κB activation study, the nuclear protein p65 content was higher in MI group (0.14 ± 0.02) ng/ml than Sham group (0.06 ± 0.01) ng/ml, but lower in MI+BR group (0.10 ± 0.02) ng/ml, allP<0.01.
Conclusion: Application of BR may improve the ventricular remodeling and cardiac function in experimental MI rats, it might be because of BR partially inhibit NF-κB activation, reduce collagen deposition and help anti-apoptosis in myocardial cells.

Objective To evaluate the protective effect and mechanism of luomaishutong(LMST)on acute myocardial ischemia-reperfusion injury in rabbits.Method Twenty-four New Zealand white rabbits were randomly divided into 3 groups:the LMST group,the control group and the sham-operated group.The AMI reperfusion model was established by removing the blockade after the occlusion of coronary artery for 2 hours.The changes of hemodynamics,oxygen free radical and clearance system were measured in all rabbits.Results (1)Compared with the control group,left ventricular systolic pressure(LVSP)and maximal changing rate of left ventricular innner pressure(?dp/dt_(max))increased remarkably in the LMST group after reperfusion,meanwhile, LVEDP decreased significantly.(2)In the control group,MDA level of cardiocyte was noticeably higher,while SOD and NOS levels were lower than in the sham-operated group.Compared with the control group,MDA level in the LMST group was significantly lower.Furthermore,SOD and NOS levels were higher in LMST group,and the infarcted area was smaller in the LMST group as well.Conclusions LMSF can protect myocardium after ischemia-repcrfusioninjury and improve cardiac function through inhibiting induced by oxygen free radicals.