Objective To observe the changes of STAT3 signaling transduction pathway and autophagy activity in human glomerular mesangial cells cultured in high glucose, as well as the effect of STAT3 on autophagy, exploring whether SAT3 further influence extracellular matrix proteins type IV collagen secretion through the regulation of autophagy. Methods Culture human renal mesangial cells under different conditions, STAT3 pathway was inhibited with specific blocking agent S3I?201 and siRNA respectively. The experiment was divided into: (1) Control group: normal glucose concentration; (2) High glucose group: divided into 12 h, 24 h, 48 h, 72 h incubation group. (3) High glucose+S3I?201 group: pretreated cells with 30 μmol/L S3I?201 (Selleck S1155) for 1 h, then incubation with high glucose for another 24 hours. (4) High glucose+STAT3?siRNA group: siRNA transfection firstly, then incubation with high glucose for 24 hours. (5) High glucose+S3I?201+3?MA group: pretreated cells with 2 mmol/L 3?MA (Selleck S2767) and 30 μmol/L S3I?201 for 1 h, then incubation with high glucose for another 24 hours. Western blot was employed to detect the protein of STAT3, p?STAT3 and autophagy related protein LC3, p62 expressions. The changes of autophagosome quantity was observed with transmission electron microscope. The extracellular matrix protein collagen IV expression was measured with ELISA. Results Compared with the control group, glomerular mesangial cells cultured with high glucose for 24h, the expressions of STAT3 and p?STAT3 increased (P<0.01), while the expression of autophagy related proteins LC3II/LC3I decreased. The expression of p62 increased and the number of autophagosome reduced under transmission electron microscope, which all indicated the decrease of autophagy activity (P<0.05). Blocking STAT3 signaling pathway with S3I?201 and STAT3?siRNA respectively, compared with high glucose group, LC3II/LC3I was up?regulated and p62 was down?regulated, and the number of autophagosome was increased significantly, which all indicated the increase of autophagy activity (P<0.05). Extracellular matrix proteins collagen IV expression of cells cultured with high glucose was higher than the control group (P<0.05), and the application of S3I?201 blocking STAT3 pathway caused type IV collagen expression to decrease (P<0.05). The application of the autophagy inhibitor 3?MA could convert the result and lead to an increase of type IV collagen expression (P<0.01). Conclusions High glucose could active STAT3 signaling pathway of human renal mesangial cell and increase STAT3, p?STAT3 expression. High glucose could inhibit autophagy activity of human renal mesangial cells. Inhibition of STAT3 pathway activation may reduce the inhibitory effect of high glucose on autophagy of human renal mesangial cells. High glucose leads to an increase of type IV collagen secretion of human glomerular mesangial cells. The activation of STAT3 pathway may increase type IV collagen secretion through negative regulation of autophagy, which eventually leads to diabetic nephropathy.

Objective To investigate the effect of nano-?-linolenic acid on the expression of cathepsin B(CB) in mice with viral myocarditis(VM).Methods Eighty male Balb/c mice were randomly divided into 4 groups:control group,myocarditis group,low-dose intervention group and high-dose intervention group,each group had 20 mice.Mice in control group were inoculated introperitoneally with eagle′s solution,every mouse in the last 3 groups was treated with 0.1 mL Coxsackie B3 virus(CVB3) intraperitoneally.Then,mice in low-dose intervention group and high-dose intervention group were treated with 60 mg?kg-1and 180 mg?kg-1 nano-?-linolenic acid solution for 7 days,respectively.Mice in control group and myocarditis group were treated with 9 g?L-1 saline for 7 days.All mice were killed on the 15th day,and the specimens of hearts and serum were conserved.Myocardial histopathology was determined with hematoxylin and eosin stain.The expression levels of myocardial CB mRNA were detected by reverse transcription polymerase chain reaction.Serum CB concentration was examined by enzyme-linked immunosorbent assay.Results The mortality rate was 0,45%,30% and 20% in control group,myocarditis group,low-dose intervention group and high-dose intervention group,respectively;the mortality rate was significantly lower in high-dose intervention group compared with myocarditis group(P0.05).The expression level of CB mRNA and serum CB concentration were markedly higher in myocarditis group than those in control group(Pa

OBJECTIVETo evaluate the effect mechanism of warm acupuncture combined with auricular point sticking therapy and its efficacy on insomnia by monitoring the level of brain neurotransmitters in the insomnia patients.

METHODSOne hundred and thirty patients with insomnia were randomized into an observation group and a control group, 65 cases in each one. In the observation group, based on the treating principle of warming yang and benefiting qi, acupuncture was applied to Xinshu (BL 15), Pishu (BL 20), Shenshu (BL 23), Yaoyangguan (GV 3), Baihui (GV 20), Neiguan (PC 6) and Shenmen (HT 7). Warm acupuncture was supplemented at Xinshu (BL 15), Pishu (BL 20), Shenshu (BL 23) and Yaoyangguan (GV 3). The treatment was given once every day. In the control group, estazolam tablets, 0. 5 to 1 mg were prescribed for oral administration, 30 min before sleep at night. The treatment of 14 days was taken as one session and 2 sessions were required in the two groups. The encephal of luctuograph technology was used to observe the sleep quality and brain neurotransmitters before and after treatment in the two groups and the efficacy was compared between the two groups.

RESULTSThe total effective rate was 83.1% (54/65) in the observation group and 87.7% (57/65) in the control group. The efficacy was similar between the two groups (P > 0.05). In the observation group, after treatment, 5-HT and GABA/Glu were all increased compared with those before treatment (P < 0.05, P < 0.01) and norepinephrine (NE) was reduced compared with that before treatment (P < 0.05). The level of each index did not change significantly before and after treatment in the control group (all P > 0.05). The regulations of 5-HT, GABA/Glu in the observation group were superior to those in the control group (all P < 0.05).

CONCLUSIONThe combined therapy of warm acupuncture and auricular point sticking method for warming yang and benefiting qi effectively improves brain neurotransmitters and essentially improves sleep quality of the patients with insomnia differentiated as yang deficiency pattern.

Acupuncture Points ; Acupuncture Therapy ; Acupuncture, Ear ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neurotransmitter Agents ; metabolism ; Serotonin ; metabolism ; Sleep Initiation and Maintenance Disorders ; metabolism ; therapy ; Treatment Outcome ; Yang Deficiency ; metabolism ; therapy ; Young Adult ; gamma-Aminobutyric Acid ; metabolism

Objective: To observe the effects of Yanggan Lidan Granule (YGLDG), a compound traditional Chinese herbal medicine, on insulin resistance in guinea pigs with induced cholesterol gallstones. Methods: Eighty guinea pigs were randomly divided into normal control group, untreated group, YGLDG group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group. Except the normal control group, gallstones were induced by high-cholesterol diet in the guinea pigs. The guinea pigs in the normal control group and the untreated group were administered with normal saline. UDCA and YGLDG were given to the guinea pigs in the corresponding groups for seven weeks. Eight guinea pigs of each group were used to measure the glucose infusion rate (GIR) by using hyperinsulinemic-euglycemic clamp technique. At the end the guinea pigs were killed and their gallstone formation was observed. Results: The gallstones in guinea pigs were identified as cholesterol stones by qualitative analysis through infrared spectrum. The incidence rate of cholelithiasis of the untreated group was 82.35% . The GIR of guinea pigs in the untreated group was obviously lowered down as compared with the normal control group. Compared with the untreated group, the GIRs of the YGLDG group and the UDCA group were obviously increased, especially in the YGLDG group. Conclusion: YGLDG may improve insulin resistance in guinea pigs with cholesterol gallstones by elevating GIR obviously.

Objective:To explore the relationship of negative life events,parent-child relationship,teacher-child relationship with the altruistic prosocial behaviors in migrant and unattended primary school children. Methods:Totally 1198 migrant children and 1631 unattended children were recruited. The dimension ofaltruistic prosocial behaviorof Child and Adolescent Prosocial Behavior Questionnaire (CAPBQ-A)was used to evaluate altruistic prosocial behaviors,Life Event Questionnaire (LEQ)was used to evaluate negative life events,parent trust and support dimensionof Social Psychological Relationship Questionnaire(SPRQ-P)to evaluate par-ent-child relationship, and teacher trust and support dimension (SPRQ-T ) to evaluate teacher-child relationship. Results:The CAPBQ-A scores were higher in migrant children than in the unattended children (P<0. 001). Being migrant or unattended children (β=-0. 07),LEQ score (β=-0. 04),SPRQ-P score (β=0. 13) and SPRQ-T score (β=0. 31 )predicted the CAPBQ-A score significantly. The SPRQ-P score had significantly stronger predictive effect on the migrant children compared to the unattended children (β=-0. 06 ). Yet the SPRQ-T score predicted the unattended children stronger (β=0. 06 ,Ps<0. 0 1 ). Conclusion:The unattended children's al-truistic prosocial behaviors are much worse than the migrant children. Personal relationships seem to play a more important role than negative life events in shaping children's altruistic prosocial behaviors. Moreover,the parent-child relationship seems to be more important to the migrant children,whereas the teacher-child relationship is more important to the unattended children.

To increase the dissolution rate and extent of valsartan, valsartan nanosuspensions have been prepared. Controlled precipitation assisted with sonication is utilized to prepare valsartan nanosuspensions, the concentration of the drug, stabilizer and costablizer had a great effect on the stability of the preparation according to the pre-experiment. So the method of central composite design-response surface is used to optimize the prescription based on the above three factors and the particle size as the response value. The software Origin 8.0 is used to draw the view of the three-dimensional effects and 2D contour map, to get the optimal prescription area. Valsartan nanosuspensions were prepared. The mean diameter and zeta potential are about 216.6 nm and -57.7 mV, respectively. Compared with the microsuspensions and commercial preparation, the dissolution of valsartan nanosuspensions was faster and the bioavailability can be enhanced to some extent.
Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; chemistry ; Biological Availability ; Chemical Precipitation ; Drug Stability ; Nanoparticles ; administration & dosage ; chemistry ; ultrastructure ; Particle Size ; Research Design ; Solubility ; Suspensions ; Ultrasonics ; methods ; Valsartan ; administration & dosage ; chemistry

The chemical investigation on Ganoderma philippii led to the isolation of sixteen compounds by silica gel and Sephadex LH-20 column chromatography. On the basis of spectroscopic data analyses, their structures were elucidated as 2, 5-dihydroxyacetophenone (1), methyl gentisate (2), (S) -dimethyl malate (3), muurola-4, 10 (14) -dien-11beta-ol (4), dihydroepicubenol (5), 5-hydroxymethylfuran carboxaldehyde (6), ergosta-7, 22E-dien-3beta-ol (7), ergosta-7, 22E-dien-3-one (8), ergosta-7, 22E-diene-2beta, 3alpha, 9alpha-triol (9), 6/beta-methoxyergo-sta-7, 22E-dien-3beta, 5alpha-diol (10), ergosta-4, 6, 8(14), 22E-tetraen-3-one (11), ergosta4, 6, 8-(14), 22E-etetraen-3beta-ol (12), 5alpha, 8alpha-epidioxy-ergosta-6, 22E-dien-3beta-ol (13), 7alpha-methoxy-5alpha, 6alpha-epoxyergosta-8-(14), 22E-dien-3beta-ol (14), ergosta-8, 22E-diene-3beta, 5alpha, 6beta, 7alpha-tetraol (15), and ergosta-5, 23-dien-3beta-ol, acetate (16). All the compounds were obtained from this fungus for the first time, and compounds 4 and 5 were isolated from the Ganoderma genus for the first time.
Ganoderma ; chemistry ; Medicine, Chinese Traditional ; Organic Chemicals ; analysis ; isolation & purification

OBJECTIVETo investigate effects of biejiajian pill (BP) on the proliferation, adhesion, and invasion of hepatoma carcinoma cells (HepG2), and to primarily explore the mechanisms for fighting against metastasis and invasion.

METHODSUsing sero-pharmacological methods, HepG2 cells were respectively cultured by high and middle dose BP containing serums and the vehicle serum. Using MTT colorimetry, cell adhesion test, and Transwell invasion test, effects of BP on the proliferation, adhesion, and invasion of HepG2 cells were detected, thus further exploring the mechanisms for fighting against the metastasis and invasion of HepG2 cells.

RESULTSHigh and middle dose BP containing serums could significantly prohibit the growth and proliferation, the adhesion and invasion of HepG2 cells on the basilar membrane. Besides, these effects were correlated with the concentrations of BP.

CONCLUSIONBP could effectively inhibit the growth and proliferation, adhesion and invasion of HepG2 cells.

Animals ; Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hep G2 Cells ; Humans ; Liver Neoplasms ; pathology ; Male ; Rats

Warfarin was the only oral anticoagulant drug , widely used in the prevention of thromboembolism events.The antithrombotic effect of warfarin has been very clear , but there are also some defects , such as that the treatment window is narrow and individual difference is very big.In recent years , the emergence of new targeted oral anticoagulant agents has provided a new choice for the anticoagulant drugs.The development of targeted oral anticoagulant drugs is reviewed , and the new challenge to warfarin is discussed.

Objective To observe the level of anti-adenovirus neutralizing antibodies and Gagspecific cellular immune responses in Macaca fascicularis immunized with different dosage of recombinant adenovirus vaccine Ad5-HIVgag by repeated intramuscular injection.Methods The Macaca fascicularis were randomly divided into four groups of 6.Different amount of the purified Ad5-HIVgag(0.99 × 1011 VP,4.94 × 1011 VP,24.68 × 1011 VP) or PBS were administered in 3 weeks interval and five times.The level of anti-adenovims neutralizing antibodies and Gag-specific cellular immune responses at different time points were detected by neutralization assay and Elispot assay respectively.Results High level of anti-adenovirus neutralizing antibodies could be detected in three groups immunized with Ad5-HIVgag at 3 weeks after first immunization.The neutralizing antibodies reached peak at 8 weeks after primary immunization,and declined slightly at late time.Significant HIV-1 Gag-specific cellular immune responses were detected in all Ad5-HIVgag immunized groups at 5 weeks post first immunization.The Gag-specific cellular immune responses declined at 12 weeks and then increased with time.Conclusion Anti-adenovirus neutralizing antibodies could be induced in Macaca fascicularis immunized with Ad5-HIVgag by repeated intramuscular injection.And the Gag-specific cellular immune responses tended to increase with the injection times.The presence of anti-adenovirus neutralizing antibodies induced by vaccination with adenovirus vectors in Ad5-naive animals did not further reduce Gag-specific cellular immune responses.