Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes and nitrite treatment reduces total triglyceride levels in the high-fat diet mice. Therefore, the present study aimed to determine the effects of nitrite on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L-02 cells were induced by incubating L-02 cells with 1.2 mmol · L(-1) oleic acid (OA) for 24 h. Secondly, steatotic L-02 cells were treated with 0.2 mmol · L(-1) sodium nitrite (SN) plus 3-methyladenine (3-MA), or chloroquine (CQ) for 24 h, and then lipid accumulation was measured with oil red O staining and triglyceride quantification. The notable steatosis could be observed in L-02 cells following exposure to 1.2 mmol · L(-1) OA for 24 h. Treatment with 0.2 mmol · L(-1) sodium nitrite reduced lipid accumulation in steatotic L-02 cells. 3-MA weakened the ability of sodium nitrite to ameliorate hepatic steatosis. Additionally, the sodium nitrite increased number of LC3-II immunostaining puncta and LC3-II protein expression was confirmed by immunofluorescence or Western blot analysis, and the effects were enhanced by CQ treatment. The number of increased cytoplasm vacuoles and lysosomes increased was confirmed by phase contrast and fluorescence microscope respectively. The increased autolysosome was detected by electron microscopy, this phenomenon could be reversed by CQ treatment. These data demonstrated that sodium nitrite enhanced the autophagic flux and decomposition of triglycerides in steatotic L-02 cells.
Adenine ; analogs & derivatives ; Autophagy ; Blotting, Western ; Cells, Cultured ; Chloroquine ; Cytoplasm ; Fatty Liver ; Hepatocytes ; drug effects ; Humans ; Lipid Metabolism ; drug effects ; Microscopy, Fluorescence ; Microtubule-Associated Proteins ; metabolism ; Oleic Acid ; Sodium Nitrite ; pharmacology ; Triglycerides

UNLABELLEDTo observe the efficacy of adefovir dipivoxil(ADV) in combination with Anluohuaxian capsule in the treatment of chronic hepatitis B (CHB) patients.

METHODS72 cases with CHB were randomly divided into two groups. 36 cases of treatment group were given ADV combined with Anluohuaxian capsule for 48 weeks. 36 cases of control group were given ADV. The levels of serum ALT, AST, Alb, TBil, HA, LN, CIV, HBV DNA and hepatic tissue were compared before and after being treated.

RESULTSAfter 48 weeks treatment,the liver function, serum fibrosis index and histology of treatment group and control group all have improved. After treatment, the two groups in the levels of ALT(t=0.746, P=0.342), AST (t=0.369, P=0.713), TBil (t=0.146, P=0.684), Alb(t=0.148, P=0.883), liver tissue inflammation mobility scoring (t=1.666, P=0.100) and HBV DNA negative rate (x2=0.141, P=0.708) were no evident difference.The level of HA, LN, CIV were significantly lower in treatment group(101.58+/-30.11, 147.89+/-41.72, 38.75+/-9.50) compared with control group(182.25+/-117.59, 181.50+/-56.96, 74.92+/-31.14) (P less than 0.05). After the treatment, the liver tissue fibrosis scoring was significantly lower in treatment group (10.61+/-2.37) compared with before the treatment (12.28+/-3.16) (P less than 0.05).There was no difference found between after the treatment (11.36+/-2.93) and before the treatment (12.17+/-3.01) in control group (P more than 0.05).

CONCLUSIONSThe results show that the treatment with ADV in combination with Anluohuaxian capsule can play promoting antifibrotic effect and significant improved liver histology of chronic hepatitis B patients.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Phytotherapy ; Treatment Outcome

Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens.
Animals ; Humans ; Phytoestrogens ; chemistry ; pharmacology ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry

OBJECTIVETo investigate the effect of phenylephrine (an α-adrenergic agonist) on alveolar fluid clearance (AFC) in ventilator-induced lung injury and the possible mechanism involved.

METHODSA total of 170 male Wistar rats were randomly allocated into 17 groups (n=10) using random number tables. Short-term (40 minutes) mechanical ventilation with high tidal volume (HVT) was performed to induce lung injury, impair active Na+ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different concentrations (1×10(-5), 1×10(-6), 1×10(-7), 1×10(-8), and 1×10(-9) mol/L) was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na(+) channel, and microtubular system on the effect of phenylephrine, phenylephrine at 1×10(-5) mol/L combined with prazosin (an α1-adrenergic antagonist, 1×10(-4) mol/L), yohimbine (an α2-adrenergic antagonist, 1×10(-4) mol/L), atenolol (a β1- adrenergic antagonist, 1×10(-5) mol/L), ICI-118551 (an β2-adrenergic antagonist, 1×10(-5) mol/L), amiloride (a Na+ channel blocker, 5×10(-4) mol/L), ouabain (a Na(+)/K(+)-ATPase blocker, 5×10(-4) mol/L), colchicine (a microtubular disrupting agent, 0.25 mg/100 g body weight), or β-lumicolchicine (an isomer of colchicine, 0.25 mg/100 g body weight) were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured.

RESULTSBasal AFC in control rats was (17.47±2.56)%/hour, which decreased to (9.64± 1.32)%/hour in HVT ventilated rats (P=0.003). The perfusion of phenylephrine at 1×10(-8), 1×10(-7), 1×10(-6), and 1×10(-5) mol/L significantly increased the AFC in HVT ventilated rats (all P<0.05). This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively (all P<0.05). The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively (both P<0.05). Colchicine significantly inhibited the effect of phenylephrine (P=0.031).

CONCLUSIONPhenylephrine could increase the AFC in HVT-ventilated rats and accelerate the absorption of pulmonary edema.

Animals ; Male ; Phenylephrine ; therapeutic use ; Pulmonary Alveoli ; metabolism ; Rats ; Rats, Wistar ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Ventilator-Induced Lung Injury ; drug therapy ; metabolism ; pathology

BACKGROUNDRecent research suggests that beta(2)-adrenergic agonists increase alveolar fluid clearance (AFC) under physiologic and pathologic conditions. It is unknown whether beta(3)-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of beta(3)-adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved.

METHODSHypoxic rats were exposed to 10% oxygen. BRL-37344 (beta(3)-adrenergic agonist) or CGP-12177 (selective beta(3)-adrenergic agonist) alone or combined with beta receptor antagonists, sodium channel blockers, or Na(+)/K(+)-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content (TLW) and AFC were measured.

RESULTSAFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride (a Na(+) channel blocker) and ouabain (a Na(+)/K(+)-ATPase inhibitor) by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177.

CONCLUSIONSThese findings suggest that beta(3)-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.

Adrenergic beta-Agonists ; therapeutic use ; Animals ; Body Fluids ; drug effects ; metabolism ; Ethanolamines ; therapeutic use ; Hypoxia ; physiopathology ; Male ; Propanolamines ; therapeutic use ; Pulmonary Alveoli ; drug effects ; metabolism ; pathology ; Pulmonary Edema ; drug therapy ; etiology ; metabolism ; Rats ; Rats, Wistar

There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility.However,the results obtained were inconsistent.Therefore,we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility.A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th,2016.A total of 20 studies with 4293 cases and 4507 controls were included.An odds ratio (OR) and a 95％ confidence interval (95％ CI) were calculated to assess the strength of the association.A cumulative meta-analysis,sensitivity analysis and assessment of the publication bias were also performed in this study.The results showed that in the overall analysis,the association between the MTHFR A1298C polymorphism and male infertility was not significant.A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model:OR=l.20,95％ CI=1.01-1.44,P=0.994;the dominant model:OR=1.23,95％ CI=1.04-1.45,P=0.996;and the allele model:OR=l.20,95％ CI=1.04-1.39,P=0.985) but not in the Caucasian population.In the stratified analyses,no significant association was observed between the different types of male infertility.This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility,especially in the Asian population.

OBJECTIVETo investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance.

METHODSThe expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed.

RESULTSThe rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis.

CONCLUSIONSPyk2 expression can be a prognostic factor to the CRC patients together with other predictors.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Focal Adhesion Kinase 2 ; metabolism ; Humans ; Male ; Middle Aged ; Prognosis

Objective To investigate the current condition of Keshan disease(KD), and inner and outer environmental selenium (Se) levels in Shandong Province, in order to provide scientific evidence for the research, prevention and control work. Methods Inhabitants from 20 villages of 8 counties in KD endemic areas were selected as subjects undergoing general physical examination and electrocardiogram (ECG). Suspicious cases were followed up by chest X-ray radiographs. Meanwhile the Se contents in hair, wheat, corn and sweet potato were measured. Results Ninety one patients with KD, including 82 with latent KD and 9 with chronic KD, were screened out of 2613 inhabitants. The total incidence of KD was 3.48% (91/2613), while the incidence of latent and chronic KD was 3.14%(82/2613) and 0.34%(9/2613) respectively. No new cases of acute or sub-acute KD were found. A total of 368 abnormal ECCs were discovered and the rate of abnormal ECG detected among surveyed population was 14.08% (368/2613). Out of 113 suspects who took X-ray, 57 cases had cardiomagaly. In 217 samples of hair, 228 samples of wheat, 214 samples of corn and 190 samples of sweet potato that were collected, the Se contents were determined by fluorescence. The average Se content in hair, wheat,corn and sweet potato were (0.406±0.090), (0.026±0.009), (0.023±0.010), (0.024±0.006)mg/kg respectively. Conclusions Current condition of KD in Shandong Province remains relatively stable. Se content was increased in the hair, nearly achieving the level in normal areas, but remains low in food.

Objective To investigate the prevalence of and predisposing factors of atopic dermatitis (AD ) in 0 - 6 year-old children in rural and urban area of Tianjin. Methods The subjects were chosen by cluster sampling from kindergartens in Tianjin's urban and rural districts. Questionnaires were designed based on the International Study of Asthma and Allergies in Children (ISAAC ) and distributed to the children's parents via the teachers. Results In this survey, 3 749 questionaires were returned, of which 3 708 were valid. The response rate was 82.7% in total, 79.3% in the rural area, and 84.9% in the urban area. The age and gender distributions were similar in the urban and rural area. The prevalence rate of AD in these children was 2.9% in total, and it was higher in the urban area than in the rural area (3.5% vs 2.4%, x2 = 3.98, P

As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.
Computer-Aided Design ; Crystallography, X-Ray ; Drug Discovery ; methods ; Ligands ; Magnetic Resonance Spectroscopy ; Peptide Fragments ; chemical synthesis ; chemistry ; Protein Conformation ; Small Molecule Libraries ; Surface Plasmon Resonance