Cytokine Profiles and Virological Marker Monitoring during 48 Weeks Peginterferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B / 生物医学与环境科学（英文）

Objective@#This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB).@*Methods@#HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks.@*Results@#A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log 10 IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05).@*Conclusion@#There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.

Effects of Buyang Huanwu Decoction on Hemorheology and Platelet Related Biological Indexes in Hyperlipidemia Model Rats / 中国药房

OBJECTIVE：To investigate the effe cts of Buyang huanwu decoction on hemorheology and platelet related biological indexes of hyperlipidemia model rats. METHODS ：Male Wistar rats were randomly divided into blank control group （10 rats）and model group （40 rats）. Blank control group was given normal diet ，and model group was given high-lipid diet for 6 weeks at least to induce hypelipidemia model. After modeling ，rats were randomly divided into model control group ，positive control group （simvastatin，0.004 g/kg），Buyang huanwu decoction low-dose and medium-dose groups （3.5，14.0 g/kg，by crude drug），with 10 rats in each group. Blank control group and model control group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，0.01 mL/g，once a day ，for consecutive 4 weeks. Thirty min after last medication ，hemorheological indexes （whole blood viscosity ，plasma viscosity ），platelet adhesion related indexes [adhesion rate，von Willebrand factor （vWF），fibronectin（FN）]，platelet release related indexes [ β-thromboglobulin（β-TG），platelet factor 4 （PF4）] and platelet fibrinolytic system related indexes [tissue plasminogen activator （t-PA），plasminogen activator inhibitor （PAI-1）]，platelet parameters （PLT，PDW，MPV，PCT，PLCR），4 kinds of coagulation parameters （APTT，TT，PT，FIB）were detected. RESULTS ：Compared with blank control group ，the whole blood viscosity （low，medium and high shear rate ），plasma viscosity，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1，PLT，MPV，PCT，PLCR and FIB in model control group were increased significantly （P＜0.05 or P＜0.01），and t-PA content was significantly decreased （P＜0.05）. Compared with model control group ，the whole blood viscosity （except for whole blood viscosity of high shear rate in Buyang huanwu decoction high-dose group ），plasma viscosity ，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1， PLT，PDW（except for Buyang huanwu decoction low-dose and high-dose groups ），MPV，PCT，PLCR（except for Byang huanwu decoction low-dose group ）and FIB were decreased significantly （P＜0.05 or P＜0.01），while t-PA content （except for positive control group ） was increased significantly （P＜0.05）. CONCLUSIONS ：Buyang huanwu decoction can significantly improve the pathological state in hyperlipidemia model rats by reducing blood viscosity and FN content ，improving platelet adhesion，enhancing fibrinolytic activity ，improving platelet aggregation ，inhibiting hypercoagulability and hyperplatelet release.

An overview of mechanism research on Helicobacter pylori pathogenic factors / 基础医学与临床

Helicobacter pylori(Hp)is considered to be closely associated with gastritis,peptic ulcer,gastric cancer and other gastrointestinal diseases,but the detail of the pathogenesis is still unclear.The past researches often fo-cused on virulence factors such as CagA(cytotoxin-associated gene/protein A),VacA(vacuolating cytotoxin A), Urease and DupA(duodenal ulcer-promoting gene/protein A),but these are not enough to demonstrate the patho-genic mechanism.Recent studies have not only revealed some new progresses of these past virulence factors but also found that Hp flagllum,adhesion protein and hemolysin play important roles in the pathogenic mechanism.

Protective effects of Huanglian Wendan Decoction aganist cognitive deficits and neuronal damages in rats with diabetic encephalopathy by inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus / 中国天然药物

Huanglian Wendan decoction (HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy (DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin (STZ) + high-glucose-fat (HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels (3 and 6 g·kg). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.

Antibacterial mechanism of emodin on methicillin staphyloccocusn aureus / 中国生化药物杂志

Objective To investigate effect of emodin on cell membrane, protein and nucleic acid synthesis of MRSA41577, and systematically investigate the anti-bacterial mechanism of emodin.Methods TTC assay was used to detected the anti-bacterial activity of emodin on MRSA 41577. Conductivity and macromolecular were detected to investigate the effect of emodin on MRSA41577 cell membrane .SDS-PAGE was used to detect the effect of emodin on the soluble protein synthesis.DAPI staining was used to detect the effect of emodin on nucleic acid synthesis.UV-visible spectrophotometric was used to detected the interaction between emodin and DNA.ResuIts Emodin has significant inhibitory activity on MRSA41577, and the minimum inhibitory concentration was 8μg/mL.After treated with 8 μg/mL emodin for 6h, compared with control group, the macromolecular and conductivity improved (71.48 ±0.026)% (P<0.01) and (2.39 ±0.102)%(P<0.05), sepreatly.Compared with control, after treated with 8μg/ml emodin for 16h,the protein reduced 32.8%, and the contents of DNA and RNA reduced (4.82 ±1.06)%(P<0.05,) and (6.67 ±0.36)%(P<0.053).The UV-visible spectrophotometric results indicated that emodin could integrate with DNA through hydrogen bond.ConcIusion The anti-bacterial mechanism of emodin mainly through damage the cell membrane , inhibit the replication and transcription of DNA through hydrogen bond , inhibit the synthesis of protein, and thus inhibit the biological function of bacteria.

Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis / 华中科技大学学报（医学）（英德文版）

Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.

Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis / 华中科技大学学报（医学）（英德文版）

Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.