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

Humans ; Occupational Diseases ; diagnosis

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

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

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.

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.

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 To evaluate the effect of high-level spinal cord injury(SCI)on the expression of mitochondrial voltage-dependent anion channel 2(VDAC2)in rat cardiomyocytes.Methods Forty-eight pathogen-free healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 2 groups(n=24 each)using a random number table:sham operation group(group S)and high-level SCI group(group H).The animals were anesthetized with intraperitoneal chloral hydrate and subjected to SCI using the modified Allen weight-drop method in group H.The spinal cord was only exposed in group S.At 6,12,24 and 48 h after SCI(T1-4),6 rats in each group were randomly selected and sacrificed,and myocardial specimens were collected from the cardiac apex for microscopic examination of the cell morphology(with a transmission electron microscope) and for determination of cell apoptosis(by TUNEL assay),expression of Bax,Bcl-2 and VDAC2 protein and mRNA in cardiomyocytes(by Western blot and real-time polymerase chain reaction,respectively).The apoptosis rate and ratios of Bax/Bcl-2 protein and mRNA were calculated.Results Compared with group S,the apoptosis rate and ratios of Bax/Bcl-2 protein and mRNA were significantly increased at T1-4,the expression of VDAC2 protein and mRNA was significantly down-regulated at T2-4(P<0.05 or 0.01),and the pathologic changes of cardiomyocytes were aggravated in group H.Conclusion The mechanism of myocardial damage is related to down-regulation of mitochondrial VDAC2 expression in cardiomyocytes and promotion of cell apoptosis in rats with high-level SCI.

Objective To investigate the therapeutic effect of the sandwich method (medical glue +gelatin sponge+medical glue) in the repair of spinal dura mater to prevent the cerebrospinal fluid leakage.Methods From February 2007 to June 2011,54 patients with spinal subdural tumors underwent excision of tumor in our hospital.According to manner of repairing spinal dura mater,all patients were classified into two groups:routine group and sandwich group.There were 16 males and 7 females with an average age of 45.2±7.2 years in the routine group,while 19 males and 12 females with an average age of 44.2±6.4 years in sandwich group.In routine group,the spinal dura mater was repaired through running locked suture.In sandwich group,the spinal dura mater was repaired through running locked suture,painting medical glue around the dural incision,covering with gelatin sponge,and painting medical glue on the surface and margin of gelatin sponge successively.Results Compared with the routine group,the total volume of postoperative drainage in sandwich group decreased significantly on the very day,the first day,the second day,and the third day,and the incidence of cerebrospinal fluid leakage decreased significantly.Before discharge,hydrops happened in 3 cases in the routine group,and got well through aspiration,continuous pressure by sandbag,and prone position.Three months after operation,5 cases from the routine group got deep hydrops under the incision and no treatment was applied to them.There was no obvious abnormality in the sandwich group.Conclusion The sandwich method can improve the repair effect of spinal dura mater injury,reduce the volume of postoperative drainage,and decrease the incidence of cerebrospinal fluid leakage