Objective To determine the mechanism of nitric oxide synthase(NOS) and prostacyclin(PGI2) acting on splanchnic hyperdynamic circulation of portal hypertention(PHT). Methods Ninety-six Sprague-Dawley rats were divided into three groups, namely, intrahepatic portal hypertension(IHPH, n=31), prehepatic portal hypertension(PHPH, n=33) and sham-operated controls(SO, n=32). Animals of each group were received indomethacin(INDO) either on a short term or long term with saline as control. Portal venous pressure, together with the concentration of nitric oxide (NO) and PGI2 in serum was measured. The constitutive nitric oxide synthase(cNOS)and inducible nitric oxide synthase(iNOS)activity in the abdominal aorta and small intestine of these rats were detrmined by spectrophotometry method. RT-PCR was performed to measure the levels of iNOS and cNOS mRNA in the arteries and guts mentioned above. Results Although INDO decreased the concentration of PGI2 in serum, the long-term INDO-treated group restored splanchnic hyperdynamic circulation in both IHPH and PHPH rats, concomitant with enhanced expression of iNOS and concentration of NO(P0.05). Conclusion Overproduction of NO inducing hemodynamic abnormalities of PHT is synthesized principally by increase of iNOS. There may be a possible interaction between PGI2 and NO in hyperhemodynamics of PHT, while PGI2 may not be a mediator in the formation and development of hyperdynamic circulatory state.

To explore the effect of high glucose on the NF-κB/IκB signal pathway in cultured rat glomerular mesangial cells. The results showed that high glucose increased the degradation of IκB-α and the translocation to nucleus of NF-κB. These changes could be reverted mostly by MG132, a proteasome inhibitor. It suggests that the activation of the NF-κB signal pathway by high glucose concentration may probably be via the ubiquitin-proteasome pathway.

Objective To investigate the effects of ketogenic amino acid ( KAA) replacement diet on insulin resistance in mice fed with high fat diet(HFD) and to analyze the possible mechanism. Methods C57BL mice were fed with a control diet, HFD, and KAA-fortified HFD(HFDKAAR)from the age of 8 weeks, and 8 weeks after HFD initiation, the HFD-fed mice were divided into two groups:one group of mice were fed the same HFD, the other group were fed HFDKAAR ( HFD→HFDKAAR ) . The metabolic evaluations were performed at the end of 16 weeks. Blood glucose levels were measured at 0, 15, 30, 60, 90, and 120 min after the injection of glucose ( 1 g/kg BW intraperitoneal glucose tolerance test, ipGTT) . The insulin,β-hydroxybutyrate, and acetoacetate levels in the plasma were measured via ELISA. The insulin resistance index ( IRI) and area under curve ( AUC) were calculated. The expression of hepatic LKB1 ( liver kinase B1 ) , AMP-activated protein kinase ( AMPK ) , and mTOR ( Mammalian target of rapamycin ) protein, and mcp-1 mRNA were measured by western blot and real-time PCR respectively. Results HFD-fed group of mice displayed significantly heavier body weight,heavier intra-abdominal fat weight, and significant deterioration of glucose tolerance at the end of 16 weeks in addition to higher insulin levels( all P<0. 05), HFDKAAR-fed mice exhibited significantly ameliorated high fat diet-induced obesity and glucose intolerance compared to the HFD-fed mice, which was associated with decreased insulin levels, IRI, AUC, and mcp-1 mRNA expression (all P<0. 05). HFD suppressed hepatic LKB1 and AMPK phosphorylation expression, and increased mTOR phosphorylation levels compared to the control diet-fed mice(all P<0. 05). In contrast, treatment with the HFDKAAR diet increased LKB1and p-AMPK expression, which was associated with suppressed p-mTOR levels compared to the HFD-fed mice(all P<0. 05). Conclusion KAA may ameliorate high fat diet-induced obesity, glucose intolerance, via normalizing the hepatic LKB1-AMPK-mTOR nutritional signal passageway. KAA replacement diet seems to be a potential nutritional intervention for the treatment for patients with metabolic defects, such as obesity, glucose intolerance, as well as metabolic syndrome.

Objective: To study the effect of arsenic trioxide (As2O3) on human pancreatic cancer cell proliferation and apoptosis (mainly early stage) in vitro. Methods: SW1990 cells line were trea ted with As2O3 at different concentration. Cell proliferation was evaluated by MTT and apoptosis by Annexin-Ⅴ-fluostaining, electron-microscopy, flow cytometry and immunocytochemical staining of Bcl-2 and Bax. Results: As2O3 and cisplatin had the same cytotoxity on SW1990. The cytotoxic effe ct on tumor cell was produced by induction of apoptosis. Twelve hours after cult ure with 10 μg/ml As2O3, much more SW1990 cells went into apoptosis than t he control. The apoptosis rate reached 24% after 48 h with the similar concentra tion of As2O3. Immunohistochemical study revealed that the expression of Bcl -2 was decreased after treated with As2O3. Conclusion: As 2O3 can depress the proliferation of SW1990 in vitro, mainly through the i nduction of apoptosis, and it is a potential agent for pancreatic cancer chemoth erapy.

Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway

Objective · To explore the effects of brisk walking on blood pressure, body mass index (BMI), and autonomic nerve activity of male elderly with hypertension in community-based health centers in Shanghai. Methods · A total of 630 elderly men received brisk walking treatment (>10000 steps/d) voluntarily, who were selected from six community-based health centers in Pudong New Area of Shanghai. Among them, 210 people stick to training for 12 weeks. According to whether suffering from hypertension, the people were assigned to hypertension intervened group (intervention group, n=110) and normal intervened group (control group 1, n=100). Blood pressure, BMI, heart rate and autonomic nerve activity before and after the training were compared. Results · After 12 weeks of training, systolic blood pressure (SBP), diastolic blood pressure (DBP) and sympathetic nerve activity of intervention group were significantly lower than those before the training (P<0.05). SBP was also significantly lower than control group 2 (P<0.05). However, heart rate, BMI, parasympathetic nerve activity and baroreceptor reflex sensitivity did not change significantly after the training (P>0.05). Conclusion · Brisk walking treatment lasting for 12 weeks can decrease blood pressure and sympathetic nerve activity in elderly men with hypertension. It is worthy to be popularized in the community.

Objective:To explore whether Tuftsin can attenuates symptoms in experimental autoimmune encephalomyelitis mouses.Methods:C57BL/6 mice were immunized with MOG35-55 peptides,and evaluated for clinical neurological score every day .10 mice of the EAE were injected with Tuftsin subcutaneously .The spinal cord were stained by the methods of Haematoxylin Eosinstain , Luxol Fast Blue stain.The mRNA expression of IL-10 and TNF-αfrom brian tissue were detected at the 28 days by RT-PC method.Results:The controlled mice had no symptoms of disease and HE ,LFB were normal.Comparison EAE group with Tuftsin group of HE,LFB,EAE group were server than Tuftsin group.The expression of IL-10 in Tuftsin group was higher than EAE group.The expression of TNF-αin Tuftsin group was lower than EAE group .Conclusion: Tuftsin can attenuates symptoms in experimental autoimmune encephalomyelitis mouses .

Objective: To study the effect of arsenic trioxide (As 2O 3) on human pancreatic cancer cell proliferation and apoptosis (mainly early stage) in vitro . Methods: SW1990 cells line were treated with As 2O 3 at different concentration. Cell proliferation was evaluated by MTT and apoptosis by Annexin Ⅴ fluostaining, electron microscopy, flow cytometry and immunocytochemical staining of Bcl 2 and Bax. Results: As 2O 3 and cisplatin had the same cytotoxity on SW1990. The cytotoxic effect on tumor cell was produced by induction of apoptosis. Twelve hours after culture with 10 ?g/ml As 2O 3, much more SW1990 cells went into apoptosis than the control. The apoptosis rate reached 24% after 48 h with the similar concentration of As 2O 3. Immunohistochemical study revealed that the expression of Bcl 2 was decreased after treated with As 2O 3. Conclusion: As 2O 3 can depress the proliferation of SW1990 in vitro , mainly through the induction of apoptosis, and it is a potential agent for pancreatic cancer chemotherapy.

Objective:To explore the quality of life in patients with primary insomnia.Methods:Comprising 85 patients diagnosed as primary insomnia and 57 healthy controls,the study analyzed and compared the differences in quality of life between the two groups.Results:(1)Compared with healthy controls,the patients with primary in- somnia decreased in quality of life.total score,Physical functions,psychological function and social function in pri- mary insomnia group were significantly lower than those in control group in score of generic quality of life inventory (score:254.9?26.4/287.1?30.4,t=-5.15,P

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.