Objective To investigate the role of serum and glucocorticoid regulated protein kinase (SGK) 1 in the inflammatory responses mediated by toll like receptors.Methods Mice were injected with lipopolysaccharide (LPS,1 mg/kg) 2 h after the pretreatment of EMD638683 (10 mg/kg) or phosphate buffered saline (PBS) as control.At the time points of 3 and 24 h,pro-inflammatory cytokines (interleukin [IL]-6,IL-12 and tumor necrosis factor [TNF]-α) in serum were measured using enzymelinked immunosorbent assay (ELISA).Livers and lung were harvested at 6 h and 24 h after the injection of LPS,embedded by optimum cutting temperature (OCT) and then stained with hematoxylin and eosin (HE).Peripheral blood mononuelear cell (PBMC) were isolated and stimulated by LPS with or without the pretreatment of EMD or LY294002.Cytokines (IL-6,IL-12 and TNF-α) were measured using ELISA.IKKα/β,IKBα and nuclear factor (NF)-κB p65 were detected by Western bolt.Data were analyzed by one way analysis of variance.Results In the model of LPS-induced endotoxin sepsis,inhibition of SGK1 induced secretion of pro-inflammatory cytokine (IL-6 [t=3.007,P＜0.05],IL-12[t=4.413,P＜0.05] and TNF-α[t=5.403,P＜0.05]),increased inflammatory cells infikration into the liver and lung within 6 h,and induced serious multiple organ damage with collapse of alveoli and fatty degeneration of liver.After 24 h,pharmacological inhibition of SGK1 with EMD638683 increased proinflammatory cytokine (IL-6 [t=18.540,P＜0.01],IL-12[t=16.520,P＜0.01] and TNF-α[t=34.880,P＜0.01]) production in human PBMC upon LPS stimulation and inhibited the phosphorylation of IKKα/ β/IKBα and nuclear factor (NF)-κB p65.Conclusions SGK1 suppresses the toll like receptor 4 mediated inflammatory responses via NF-κB.

Objective To study the feasibility of artificial immune system(AIS)in assistant designing of computer for new Chinese herbal compounds with anti-infectious function.Methods A group of Chinese herbal drug compounds from Treatise on Exogenous Febrile and Miscellaneous Diseases were selected as training samples.Serum was obtained from mice which were infected by Staphylococcus aureus and ig administrated with the various Chinese herbal compounds.The inhibition ability against S.aureus of the serum was tested and input into an artificial neural network(ANN)together with the characters of the every Chinese herb included in those compounds.The ANN was optimized using AIS so that it can predict the inhibitory ability against S.aureus of the Chinese herbal compounds according to the characters of Chinese herbs included in those compounds.After that the computer generated a number of Chinese herbal compounds randomly,calculated their inhibitory ability against S.aureus and output those among the top levels,so as to verify whether the predictions were correct or not.Results After verification,the Chinese herbal drug compounds designed by computer could significantly raise the serum's inhibitory ability against S.aureus.Conclusion The computer can be an assistant for designing new Chinese herbal compounds with anti-infectious function

Objective To construct a retrovirus-mediated expression system containing double strands DNA for RNA interference on human Notch1 gene and study its inhibitory effect on human glioma cell lines U251 and CHG-5 in vitro.Methods A recombinant retroviral vector pSiRNA-Notch1 was generated by cloning a double strands DNA for RNA interference on human Notch1 gene into a retroviral vector Psilencer 5.1-H1 Retro.Human glioma cell lines U251 and CHG-5 were infected with the viral supernatant from the PT67 clones.After 3 d,the viability,Notch1 mRNA and protein of the transfected cells were examined by WST-8 assay,RT-PCR and Western blot.Results The pSiRNA-Notch1 recombinant retroviral vector had been constructed correctly.The titer assayed on NIH3T3 cells was up to 224?104 cfu/ml.Three days after transfection,the viability,Notch1 mRNA and protein of the transfected cells decreased significantly.Conclusion The constructed pSiRNA-Notch1 retroviral vector shows effective inhibition effect on the viability in human malignant glioma cells,with potential utility in the gene therapy for human malignant glioma.

Obesity is an established risk factor for endometrial cancer. Leptin, a secreted protein of the ob gene by white adipose tissue, plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic cancer cells. However, a direct role for leptin in endometrial cancer has not been demonstrated. In the present study, the effect of leptin on the proliferation of Ishikawa endometrial cancer cells was investigated as well as the possible mechanism(s) underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors. The expression of leptin receptor (ObRb) in Ishikawa cells was detected by RT-PCR and Western blotting. The cells after serum starvation, were treated by leptin with various concentrations (0, 10, 50, 100, 150 ng/mL) for different durations (6, 12, 24 h). The effect of leptin treatment on cell proliferation was examined by MTT assay. Meanwhile, inhibitory effect of Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) inhibitor AG490 or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on the proliferation of Ishikawa cells induced by leptin was also studied. Ishikawa cells were treated with 100 ng/mL leptin for various periods (0, 20, 40, 60 min), and the levels of STAT3 phosphorylation and ERK1/2 phosphorylation were examined by Western blotting. The results showed that leptin induced the phosphorylation of STAT3 and the activation of ERK1/2 in a time- and dose-dependent manner in the Ishikawa endometrial cancer cells. Blocking STAT3 phosphorylation with the inhibitor AG490, or blocking ERK1/2 activation by the specific ERK1/2 kinase inhibitor, PD98059, abolished leptin-induced proliferation of Ishikawa cells. In addition, leptin was found to potently induce the invasion of endometrial cancer cells in a Matrigel invasion assay. Leptin-stimulated invasion was effectively blocked by pharmacological inhibitors of STAT3 (AG490) and ERK1/2 kinase (PD98059). These results suggested that leptin promotes endometrial cancer growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways and therefore blocking its action at the receptor level can be a rational therapeutic strategy.

The growth and development of plant is affected by environmental factors that include light,temperature and water. Many cis-elements that are response to these elicitors interact with transcription factors, and regulate the expression of target genes. It concludes by pointing out recent studies of cis-elements and transcription factors in the plant environmental response promoters, such as light, temperature and water inducible promoter. The molecular mechanisms of gene expression regulated by environmental factors was discussed. This is important to study the mechanisms that plant adapt the environment.

OBJECTIVETo study curative effect of chronical hepatitis B with treatment of integrative traditional Chinese and western medicine.

METHOD115 cases of HBeAg and/or HBVDNA positive chronical hepatitis B were randomly divided into two groups in control. The first group treated by traditional Chinese medicine (TCM)-Fufang Huangqi granule and the second treated by intergrative traditional Chinese and western medicine (ICWM)-Fufang Huangqi granule and lamivudine for at least 24 weeks.

RESULTThe positive rate of HBVDNA at 12, 24 weeks, and the positive rate of HBeAg at 24 weeks in TCM are markedly lower than those of before treatment (P < 0.01). The positive rate of HBeAg and the positive rate of HBVDNA in ICWM are markedly lower than those of before treatment both at 12, 24 weeks (P < 0.01). The average values of HBVDNA are markly lower than before treatment in two groups at both 12,24 weeks (P < 0.01). At 12 weeks, the negative-turning rate of HBVDNA in the ICWM group is 79.17%, which shows significant difference in comparision with 40.00% in the TCM group (P < 0.01). The negative-turning rate of HBeAg in the ICWM group is 26.92%, which shows no significant difference in comparision with 32. 08% in the TCM group. At 24 weeks, the negative-turning rate of HBVDNA in the ICWM group is 85.71%, which shows significant difference in comparision with 50.00% in the TCM group (P < 0.01). The negative-turning rate of HBeAg in the ICWM group is 36.36%, which shows no significant difference in comparision with 28.57% in the TCM group. At 12 weeks,the total effective rate of the ICWM group is 96. 43%, which shows significant difference in comparision with 71.26% in the TCM group (P<0.01). At 24 weeks, the total effective rate of the ICWM group is 88. 00%, which shows significant difference in comparision with 67.61 % in the TCM group (P < 0.01). The average values of ALT and AST are markly improved than those of before treatment in two groups (P < 0.01). The average values of ALB is markly higher than before in TCM groups after 24 weeks treatment (P < 0.01).

CONCLUSIONFufang Huangqi granule integrated with lamivudine possesses a better effect for counteracting the hepatitis B virus and improving the liver functioin than only itself.

Adolescent ; Adult ; Aged ; Albumins ; metabolism ; Anti-HIV Agents ; therapeutic use ; Astragalus membranaceus ; chemistry ; DNA, Viral ; blood ; Drug Combinations ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Plants, Medicinal ; chemistry

Objective To investigate the relationship of impact stress distribution and stress wave dissemination with temporal bone fracture. Methods Twelve donated fresh corpse were selected and impacted with driving force of 800 kPa, 1 200 kPa and 1 400 kPa to establish the model of impact temporal bone fractures. With aid of three-dimensional stereochemical structure image of 64-slice CT, the vitodynamic distribution and dissemination of impacted temporal bone was calculated by using computer simulation. Results (1) The instant velocity, acceleration and energy of impact as well as displace-ment scope of the hammer increased with higher driving force in the tempus. (2) Instantaneous impact of the temporal bone resulted in Von Mises stress concentration area around the impact point. The stress was weakened suddenly in the skull-brain tissue coupling place but later accumulated in the skull base. (3) Only ipsilateral linear fracture occurred when the driving force of impact was 800 kPa. While impact dif-ferent degrees of depressed fractures could be seen and one case showed secondary fracture of the opposite side when the driving force of impact was 1 200 kPa. The impact with driving force for 1 400 kPa begot complex ipsilateral fractures, secondary fracture of the opposite side and skull basal fracture. (4) Frac-ture line of the temporal bone accorded with impact stress concentration area. Conclusions All pa-rameters, stress distribution and dissemination of impact are in accordance with temporal bone fracture during impaet process of the temporal bone, which is of vital significance for diagnosis and protection of impact temporal bone fractures.

OBJECTIVETo compare the difference in depression relief in the treatment of depressive disorder at the acute stage between the combined therapy of acupuncture and 5-HT (5-hydroxytryptamine) selective serotonini reuptake inhibitors (SSRIs) and the single application of SSRIs and explore the impact on the imbalance of 5-HT and TH1/TH2.

METHODSNinety cases of depressive disorder at the acute stage were randomized into a combined therapy group and a medication group, 45 cases in each one. In the medication group, SSRIs were prescribed forl oral administration, once or twice a day, continuously for 4 weeks. In the combined therapy group, on the basis of treatment as the medication group, acupuncture was combined. The main acupoints were Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), Fengchi (GB 20), Dazhui (GV 14) and Sishencong (EX-HN 1), once every two. days, continuously for 4 weeks. Before treatment, and after the 1st, 2nd and 4th weeks of treatment, the Hamilton depression scale (HAMD) was used to evaluate the depression severity. Separately, before and after the 4 weeks of treatment, the levels of serum 5-HT, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-10 (IL-10) were determined and compared with those in 45 cases of the healthy group.

RESULTSHAMD score was reduced in the 1st, 2nd and 4th weeks of treatment as compared with that before treatment in the combined therapy group (all P<0 01). HAMD score was reduced in the 2nd and 4th weeks of treatment as compared with that before treatment in the medication group (all P<0. 01). HAMD scores in the combined therapy group were lower than those in the medication group in the 1st, 2nd and 4th weeks of treatment (all P< 0. 01). Before treatment, in the combined therapy group and the medication group, the levels of serum 5-HT, IL-4 and IL-10 were all lower than those in the healthy group (all P<0. 01); the levels of IL-1β and IL-6 were higher than those in the healthy group (all P<0. 01). In the combined therapy group and the medication group, the levels of 5-HT, IL-4 and IL-10 in 4 weeks of treatment were all increased as compared with those before treatment (all P<0. 01), and the levels of IL-1β and IL-6 were lower than those before treatment (all P<0. 01). In the combined therapy group, the levels of IL-1β and IL-6 in 4 weeks of treatment were lower than those in the medication group, and the levels of 5-HT, IL-4 and IL-10 were higher than those in the medication group (P<0. 01, P< 0. 05).

CONCLUSIONThe combined therapy of acupuncture and SSRIs achieves much quicker and more effective re-' sult for relieving depression in the patients of depressive disorder as compared with simple oral administration of' SSRIs, and much more contributes to adjust the imbalance of serum 5-HT and TH1/TH2.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Antidepressive Agents ; administration & dosage ; Combined Modality Therapy ; Depressive Disorder ; blood ; drug therapy ; therapy ; Female ; Humans ; Interleukin-10 ; blood ; Interleukin-1beta ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged ; Serotonin ; blood ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Young Adult

To investigate the effects of telmisartan on steatohepatitis (NASH) in rats by activating peroxisome proliferator-activated receptor gamma (r). Thirty male SD rats were randomized into normal control group, NASH control group and telmisartan prevention group. Normal control group was given standard food and the other two groups were given high fat diet for 16 weeks to induce NASH. Prevention group was given telmisartan (5 mg.kg-1.d-1) for 4 weeks by intragastric adminstration after 12 weeks. At the end of the 16th week, all the rats were sacrificed. Pathological changes of liver were observed by optical microscopy. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), fasting blood glucose(FBG), fasting insulin(FINS), HOMA-IR(homeostasis model assessment insulin resistance), Serum TNF-a and adiponectin were detected and analyzed.Western blot and RT-PCR were used to detect PPARr expression in hepatic tissues on protein and mRNA levels. (1) Rats were successfully modeled. The liver tissue samples were divided into 4 degrees (F0 - 4) based on total fatty degeneration of liver cells.There was one rat reached F3 and nine rats reached F4 in NASH group, one rat reached F1, six rats reached F2 and three rats reached F3 in prevention group. Inflammatory activity scores of hepatic tissues in the model group were 2.67+/-0.25, while that in the control group was 0 (U=15 and P is less than to 0.01), in the prevention group were 2.67+/-0.25 and 1.36+/-0.12 (U=24 and P is less than to 0.05 ). (2) The levels of serum ALT, AST, FBG, FINS, TNFa and HOMA-IR in the model group were increased than those in the control group( the vaules of q were 13.130, 6.472, 6.909, 26.619, 14.591 and 49.683 respectively, P less than 0.01). The levels of serum ALT, FINS, FBG, TNFa and HOMA-IR in the prevention group were decreased as compared to the model group (the vaules of q were 7.024, 4.145, 14.829, 13.195 and 31.991 respectively, P less than 0.01 ). (3) The serum adiponectin, PPARrmRNA and protein in liver tissues of the model group were lower than those in the control group (q values were 10.696, 8.679 and 16.762 respectively, P is less than to 0.05).The data in the prevention group were higher as compared to the model group(q values were 3.879,3.079,6.400, P is less than to 0.05 respectively). HOMA-IR was positively correlated with the expression of TNFa but negatively correlated with the expression of adiponectin (r = 0.927, P is less than to 0.01; r = -0.891, P is less than to 0.01, respectively). Telmisartan may has preventive effect on rats with steatohepatitis (NASH) by a mechanism of activating peroxisome proliferator-activated receptor r.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Fatty Liver ; Insulin Resistance ; Non-alcoholic Fatty Liver Disease ; Rats ; Rats, Sprague-Dawley

Objective To investigate the characteristics of renal hemodynamic and the esoteric prostacyclin(PGI2),thromboxane A2(TXA2)level in children with early Henoch-Schonlein purpura(HSP),and study the function of TXB_2/6-Keto-prostaglandin F(6-Keto-PGF_(1?))(T/K)numerus in early changes of kidney injury.Methods Children involved in the experiment were dicided into 3 groups.Thirty-one patients with HSP,divided into 2 groups according to routine urianlysis:children with HSP without renal damage group(n=16)and Henoch-Schonlein purpura nephritis(HSPN)group(n=15).Control group with 16 healthy children,their age and sex match with the other 2 groups.The urine of all children,including the children in control group,was sampled in 24 hours.The urinary production of the samples were kept in the freezer at-20 ℃.The radioimmunoassay was applied to determine the 6-Keto-PGF_(1?),TXB_2 quantitatively,and calculate the number of T/K.In the early morning the children accept the Doppler arteria renalis sonography with an empty stomach to determine the Vmax of the period of contraction of the arteria renalis the Vmin of diastolic phase and the resistent index(RI).SPSS 13.0 software was used to analyze the data.Results 1.The renal hemodynamic indicated a change of high velocity and resistance,the masculine rate(83.9%)was ob-viously higher than that in routine urinalysis(48.4%)(?2=5.79 P0.05).The RI in the former group(0.798?0.165)was much higher than that in the other one(0.637?0.116)(t=4.02 P