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73; P less then 0.00001), respectively. For the subgroups PD-L1 expression (negative and high), there were benefits both observed in the PFS and OS in two sub-groups with atezolizumab (P 0.05). However, in the low expression of PD-L1 group, the subjects who received atezolizumab achieved PFS (OR 0.70; 95% CI 0.58-0.84, P=0.0002) advantage but OS advantage (OR 0.91; 95% CI 0.62-1.33, P=0.62). Conclusion In low expression of PD-L1 subgroups, a benefit was observed for PFS but OS. However, the status of PD-L1 expression cannot be recommend as prognostic biomarker to support the decision who will benefit from atezolizumab.Recently we isolated CN-3, a new asterosaponin from starfish Culcita novaeguineae, and reported that asterosaponin arrests glioma cell cycle via SCUBE3. However, the multiple mechanisms underlying CN-3 anti-glioma action remains poorly known. Thus, the focus of this study was to evaluate the inhibitory effect of CN-3 on human glioma cells and its underlying molecular mechanisms. U87 and U251 cells were incubated with various concentrations of CN-3, and CCK-8, transmission electron microscopy, ICELLigence, TUNEL, flow cytometry, N-acetyl--cysteine, and western blot were conducted. As a result, it was found that CN-3 significantly inhibited U87 and U251 cell viability and proliferation in a time- and dose- dependent manner, and also induced mitochondrial apoptosis. Furthermore, we detected that CN-3 downregulated PI3K, P-Akt, AKT and BCL-2, and upregulated cytochrome C and BAX in U87 and U251 cells. Moreover, ROS triggered the inhibition and cell apoptosis for CN-3 via inactivation of P-Akt and activation of cytochrome C. A-674563 nmr In conclusion, these findings suggest that CN-3 may be a promising candidate for the development of a therapy of glioma.In this study, we treated esophageal cancer (EC) cell lines, TE1 and KYSE450 with coptisine (COP) and investigated the biological effects of COP in EC cells. Our results showed that COP inhibited the cell viability and proliferation of EC cells, and COP induced G2/M phase arrest of EC cells and decreased the expression of claudin-2, p-cdc2, CDK1 and cyclin B1. In addition, we found the reduction of p-p38 and p-ERK1/2 in EC cells treated with COP. The effects of COP on pro-cell cycle arresting were reversed after combined with p38 and ERK1/2 inhibitors. Overall, these findings indicate that COP may possess potential for anti-tumor effects in EC and may contribute to the development as anti-cancer agents.The effects of eight oral anti-coronavirus drugs (lopinavir, ritonavir, chloroquine, darunavir, ribavirin, arbidol, favipiravir, oseltamivir) on the metabolism of four specific glycosides (polydatin, geniposide, quercitrin, glycyrrhizin) and on the activities of three major glycosidases (β-glucosidase, α-rhamnosidase, β-glucuronidase) from gut microflora were explored in vitro and determined by LC-MS/MS. The metabolism of polydatin, geniposide, quercitrin and glycyrrhizin was significantly inhibited by one or several anti-coronavirus drugs of 100 μM around 1 h and 4 h (P500 μM). The consistency between gut microflora and glycosidase system indicated that the inhibition of darunavir on the activity of β-glucosidase and β-glucuronidase may be the main reason for affecting the metabolism of geniposide, glycyrrhizin and polydatin in gut microflora. However, for the inhibition of darunavir and chloroquine on the metabolism of quercetrin, there was no correlation between gut microflora and α-rhamnosidase system. Assessing the risk of HDI mediated by glycosidases in gut microflora may be conducive to the safety and efficacy of combining traditional herbal and Western medicine for the treatment of patients with Covid-19.Faldaprevir (FDV), a substrate of CYP3A/P-glycoprotein (P-gp), is a selective inhibitor of the hepatitis C virus (HCV) NS3/4 protease. FDV is currently under clinical development for application in interferon-free treatment regimens for patients with chronic HCV infection. Understanding the drug-drug interaction potential of FDV is critical, as certain drug combinations may facilitate the more rapid achievement of steady-state-that is, the ideal drug concentration and balanced metabolic cycle of absorption and elimination that optimize drug efficacy. We thus conducted this study to investigate the effect of itraconazole (ICZ), a strong inhibitor of CYP3A and a moderate inhibitor of P-gp, on the pharmacokinetics (PK) of FDV. Eighteen healthy male and female volunteers participated in this open-label, fixed-sequence study. FDV 120 mg twice daily (BID) was administered on Day 1, followed by 120 mg once daily (QD) from Day 2 until the end of the 10-day study; after 6 days of FDV alone, ICZ 200 mg was added to FDV for an additional 4 days (BID on Day 7 and QD from Day 8 to Day 10). Intensive PK sampling was performed after 6 days of FDV treatment and again after 4 days of combined FDV/ICZ treatment. The adjusted geometric mean (gMean) ratios (%) of area under the concentration curve over dosing interval at steady-state (AUCτ, ss) and maximal concentration at steady-state (Cmax, ss) for combined FDV/ICZ treatment vs. FDV treatment alone were 198.6% and 180.6%, respectively, with 90% confidence intervals (CIs) of 182.4-216.1 and 165.7-196.9. Administration of FDV alone or in combination with ICZ was observed to be safe and well-tolerated. Co-administration with ICZ, however, resulted in an approximately two-fold increase in FDV steady-state exposure. Furthermore, FDV required no dosage adjustment when co-administered with ICZ.Nanoparticles (NPs) promise to address current limitations for treating acute pancreatitis (AP) via inflammatory cell-mediated sequestration. However, very few studies have explored the influence of NP size on their behavior in different stages of AP. The present work investigated the biodistribution of IR780 loaded mesoporous silica nanoparticles (MSNs) with sizes of 60, 150 or 300 nm after intravenous administration to rats of mild AP (MAP) or severe AP (SAP). Four hours after administration, MSN150 was present to a much greater extent in the pancreas than MSN60 or MSN300, irrespective of disease severity. MSN150 was present to a lower extent in pancreas, intestine and ascites in SAP than MAP rats, indicating weaker passive targeting in SAP rats. This may reflect greater blood loss and slower blood flow in SAP. These findings may guide the rational engineering of NPs with respect to particle size and disease severity for AP therapy.