The challenge of the emergence of drug-resistant influenza strains, which is caused by wide spread utilization of direct-acting antivirals (DAAs), accelerates the research and exploration towards host targeted agents. In contrast to DAAs targeting viral replication components, host targeted agents, which regulate host factors and pathways linked to viral replication, can interfere the replication of influenza. Additionally, the innate immune system is activated by influenza during the early stage of infection, so manipulating the innate immune response may prevent the viral infection. However, the excessive inflammatory response induced at the late phase of influenza infection would lead to severe tissue injures. Thus, it is very important to explore drugs with anti-inflammatory actions to suppress these immune imbalances and tissue injures. Here we overview the current progresses about host targets related to anti-influenza drugs.
Anti-Inflammatory Agents ; pharmacology ; Antiviral Agents ; pharmacology ; Humans ; Immunity, Innate ; Influenza, Human ; drug therapy ; Virus Replication

Adult ; Cerebrospinal Fluid Rhinorrhea ; surgery ; Endoscopy ; adverse effects ; Humans ; Male ; Pneumocephalus ; etiology

Objective To investigate the effects of glycyrrhizin on gene expression of transforming growth factor(TGF)-?signaling pathway of hepatic stellate cell(HSC)in mice by gene microarray tech- nique.Methods The HSCs were isolated from mice and cultured in vitro.Then the mice were divided into control group,TGF-?_1 group(5 ng/ml) or TGF-?_1(5 ng/ml)combined with glycyrrhizin(100?mol/L) group.The cells were collected after 10 hours to extract RNA.A cDNA microarray(GEArray~(TM) Q) targeting TGF-?/BMP signal transduction was used to screen the genes which showed significant changes in expression of TGF-?pathway of HSC by glycyrrhizin.Results The microarray analysis showed that 16 genes(16.7%),such as Smad2,Smad3,Smad7,CoL3A1,CoL1A2,and PAI-1,were upregulated by TGF-?_1 and then down-regulated by glycyrrhizin.Five genes(5.2%)(including BMP7,IGFbp3 and etc.)downregulated by TGF-?_1,were then up-regulated by glycyrrhizin.Finally,2 genes upregulated by TGF-?_1 were then up-regulated predominantly by glycyrrhizin in HSC(T?R2,betaglycan).Changes in some genes,such as Smad2 Smad3,Smad7,were further confirmed to be coincided with cDNA microarray by semi-quantitative RT-PCR.Conclusions The anti-fibrosis mechanisms of glycyrrhizin may be through to interference of TGF-?signaling pathway,decrease the synthesis and increase the degradation of collagen.

Objective To investigate the anti-inflammatory activity of the main active ingredients in the dried stem bark of Daphne giraldii Nitsche.Methods Severialchemical compounds like vladinol D, pinoresinol, daphneticin, daphnoretin, daphnetin, giraloid A and giraldoid B were isolated from the stem barks. The CCK-8 experiemnts were analyzed for the cytotoxicity study. The cells were divided into the control group, the model group and the treatment group according to random number table method. The control group and the model group were added with 50μl culture medium. Moreover, treatment group was added with different concentrations (50.00, 25.00, 12.50, 6.25, 3.12μg/ml) of the solutions of giraloid A, giraldoid B and daphneticin. Then, RAW264.7 cells were treated with 50μl LPS (4μg/ml) for 24 h in the model group and treatment group. Griess reagent was used to determine the amount of NO release, and the secretion of TNF-α was detected by ELISA kit.Results Cytotoxicity test indicated that giraldoid A (50.00μg/ml), giraldoid B (50.00μg/ml) and daphneticin (50.00μg/ml) showed noobvious cytotoxicity. Giraldoid B (12.50, 25.00, 50.00μg/ml) could inhibit the production of NO (271.86% ± 20.92%, 256.48% ± 20.92%, 199.31% ± 15.16%vs.358.62% ± 28.64%) and  TNF-α (647.87% ±115.79%, 618.42% ± 87.52%, 588.33% ± 87.94%vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Giraldoid A (25, 50μg/ml) could inhibit the production of NO (234.99% ± 34.28%, 167.36% ± 25.76% vs.358.62%±28.64%) and TNF-α (691.76% ± 60.37%, 534.01% ± 41.60% vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Daphneticin (12.5, 25, 50μg/ml) could inhibit the production of NO (283.89% ± 36.69%, 243.08% ± 48.19%, 225.92% ± 33.67% vs.358.62% ± 28.64%) and TNF-α (713.77% ± 121.96%, 670.62% ± 18.70% vs. 1035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group.Conclusions Giraldoid A, giraldoid B and daphneticin exhi bited anti-inflammatory effect through inhibiting the release of NO and the production of TNF-α in RAW264.7 induced by LPS.

Humans ; Occupational Diseases ; diagnosis

Female ; Humans ; Hydrocarbons, Chlorinated ; poisoning ; Male ; Middle Aged ; Occupational Diseases

There is a variety of gut microbiota in human body, which is closely associated with the health and disease. Normal gut microbiota can produce colonization resistance to pathogens. Antibiotics can affect the composition of gut microbiota and change the intestinal microenvironment, resulting in intestinal microecological disorders, which in turn cause intestinal pathogenic infections and other diseases. In this paper, the concept of intestinal microecology, the mechanism of intestinal colonization resistance, the effect of antibiotics on intestinal microecology, and the treatment methods were reviewed, aiming to provide the information for the rational use of antibiotics and the development of more effective treatment methods to maintain the stability of intestinal microecology.

0.05).The most common toxicity was neutropenia and nausea.There are no serious nausea,damage of liver and kidney functions and grade 4 neutropenia in the study group.The side-ef- fects,in the study group,such as hemorrhage,infection,medicine outleakage,catheter obstruct,catheter slough,gastric-intestinal perforation,and fever did not appear.Conclusion Although this study was conduct- ed in a small number of patients and short time,compared with the control group,the study group had a ben- eficial effect in peritoneal recurrence after curative gastrectomy for advanced gastric cancer and had less side effect and good toleration.It played a role in enhancing 1-year overall survival rate.The combination of intra- venous and intraperitoneal chemotherapy after gastrectomy may have better treatment effect on gastric cancer than that of intravenous chemotherapy alone.The randomized controlled trials are required.

Objective:This work aims to investigate diallyl disulfide (DADS) inhibition of cell migration and invasion in human colon cancer SW480 cells through the Rac1-ADF/cofilin1 pathway. Methods:The potential of cell migration and invasion was examined by scratch healing assay and transwell membrane assay. The expression of Rac1-ADF/cofilin1 pathway was detected by RT-PCR and Western blot. Results:After the SW480 cells were treated with 40 and 50 mg·L-1 of DADS for 24 h, the number of transmembrane cells through the Matrigel obviously decreased by 57.12%and 64.59%, respectively (P<0.05). After cell treatment for 48 h, the cell migration rates were 23.23%and 12.87%, which were significantly lower compared with the control group (75.86%;P<0.05). After the cells were treated with 45 mg·L-1 of DADS for 24 and 48 h, the expression of Rac1, Rock1, PAK1, LIMK1, and destrin mRNA respectively decreased compared with the control group (P<0.05). However, no significant difference was observed in the expression of cofilin1 mRNA (P>0.05). After the treatment with 45 mg·L-1 of DADS for 6, 12, 24, and 48 h, the expression of Rac1, Rock1, PAK1, LIMK1, and Destrin proteins respectively decreased in a time-dependent manner compared with the control group (P<0.05). However, no significant differences were observed in the expression of the cofilin1 protein (P>0.05). Moreover, the expression of p-LIMK1 and p-cofilin1 notably decreased in a time-dependent manner (P<0.05). Conclusion:DADS inhibits cell migration and invasion, which is related to the down-regulation of Rac1, Rock1, PAK1, LIMK1, p-LIMK1, p-cofilin1, and destrin through the Rac1-ADF/cofilin1 pathway.

To explore the effect of advanced glycation end-products(AGEs)on cell viability and level of reactive oxygen species(ROS)in MIN6 cells. After intervention of various concentrations(100,200, and 400 mg/L)of AGEs for some time, cell viability was detected by MTT assay. 2', 7'-dichlorofluorescein diacetate(DCFH-DA)was used as a reactive oxygen species capture agent. The fluorescent intensity of 2', 7'-dichlorofluorescein(DCF), which was the product of cellular oxidation of DCFH-DA, was detected by flow cytometry. The level of ROS and insulin secretion was thus measured. Viability of MIN6 cells was inhibited by AGEs in a dose and time dependent manner(P＜0.05).Intracellular fluorescent intensity of DCF was markedly elevated in the AGEs groups as compared with that in the control group(P＜0.05).Insulin secretion was decreased in the AGEs groups than that in the control group(P＞0.05). The results suggest that AGEs inhibit the viability and induce oxidative stress in MIN6 cells by overproduction of ROS.