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

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.

Humans ; Occupational Diseases ; diagnosis

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

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.

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.

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.

In this study, the regulatory effects of chlorogenic acid (CGA) on the expression of programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC), as well as the role of interferon γ (IFN-γ), has been discussed using both in vitro and in vivo animal models. ESCC murine model was established according to the standard operating procedures (SOP) of Animal Experiment Center of Institute of Materia Medica, Chinese Academy of Medical Sciences. The expression of PD-L1 in esophageal tissues of murine models was analyzed using the microarray assay. Then, the results were verified by qRT-PCR, Western blot and immunohistochemistry (IHC) staining, the molecular mechanism was explored in KYSE180 and KYSE510 ESCC cells in vitro. The results showed that CGA could suppress the expression of PD-L1 in tumor tissues in murine models significantly, rather than the expression in KYSE180 and KYSE510 ESCC cells in vitro. However, after the pretreatment of IFN-γ, the expression of PD-L1 was significantly increased, then it was down-regulated by CGA in both dose- and time-dependent manner. Meanwhile, the expression of interferon regulatory factor 1 (IRF1), an upstream regulatory factor of PD-L1, was suppressed by CGA in both KYSE180 and KYSE510 pretreated with IFN-γ, which was consistent with the expression of PD-L1. These results indicate that CGA down-regulates the expression of PD-L1 in ESCC via IFN-γ-IRF1 signaling pathway, providing the molecular theoretical basis for exploration of new treatment of ESCC.

The role of hydrogen sulfide (H2S) in portal hypertension (PH)-induced esophagus-gastric junction vascular lesions in rabbits was observed.The rabbit PH models were established.The animals were randomly divided into the following groups:normal,PH,PH+sodium hydrosulfide (PH+S),PH+propargylglycine (PH+PPG).The plasma H2S levels,apoptosis of esophageal-gastric junction vascular smooth muscle cells,and the expression of nuclear transcription factor-κB (NF-κB),p-AKT,Iκ Ba and Bcl-2 were detected.The cystathionine γ lyase (cystathionine-gamma-splitting enzyme,CSE) in the junction vascular tissue was measured.The results showed that the plasma H2S levels and the CSE expression levels had statistically significant difference among different groups (P＜0.05).As compared with PH group,plasma H2S levels were declined obviously (11.9±4.2 vs.20.6±4.5,P＜0.05),and CSE expression levels in the junction vascular tissue were notably reduced (1.7±0.6 vs.2.8±0.8,P＜0.05),apoptosis rate of vascular smooth muscle cells per unit area was significantly decreased (0.10±0.15 vs.0.24±0.07,P＜0.05),and the expression levels of p-AKT and NF-κB were significantly decreased (2.31±0.33 vs.3.04±0.38,P＜0.05;0.33±0.17 vs.0.51±0.23,P＜0.05),however,Iκ Ba and Bcl-2 expression increased obviously (5.57±0.17 vs.3.67±0.13,P＜0.05;0.79±0.29 vs.0.44±0.36,P＜0.05) in PH+PPG group.As compared with PH group,H2S levels were notably increased (32.7±7.3 vs.20.6±4.5,P＜0.05),the CSE levels in the junction vascular tissue were significantly increased (6.3±0.7 vs.2.8±0.8,P＜0.05),apoptosis rate of vascular smooth muscle cells per unit area was significantly increased (0.35±0.14 vs.0.24±0.07,P＜0.05),and the expression levels of p-AKT and NF-κB were significantly increased (4.29±0.49 vs.3.04±0.38,P＜0.05;0.77±0.27 vs.0.51±0.23,P＜0.05),yet Iκ Ba and Bcl-2 expression decreased significantly (3.23±0.24 vs.3.67±0.13,P＜0.05;0.31±0.23 vs.0.48±0.34,P＜0.05) in PH+S group.It is concluded that esophagus-gastric junction vascular lesions happen under PH,and apoptosis of smooth muscle cells is declined.H2S can activate NF-κB by the p-AKT pathway,leading to the down-regulation of Bcl-2,eventually stimulating apoptosis of vascular smooth muscle cells,easing PH.H2S/CSE system may play an important role in remission of PH via the AKT-NF-κB pathway.