PCSK9 E670G polymorphism increases risk of coronary artery disease in a Chinese Han population.

OBJECTIVE: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world. The proprotein convertase subtilisin/kexin type 9 (PCSK9) E670G polymorphism has been reported to be associated with variability in levels of low density lipoprotein cholesterol, a risk factor for CAD. However, the relationship between PCSK9 E670G and CAD is still not fully elucidated. METHODS: A total of 225 patients and 189 control subjects were recruited in this study. DNA was extracted from peripheral blood samples and was genotyped by mass array method. In addition, we also conducted a meta-analysis of case-control studies to elucidate the relationship of CAD and polymorphism. RESULTS: The GG genotype of PCSK9 E670G was associated with a higher risk of CAD [odds ratio (OR) 2.994, 95% confidence interval (CI): 1.174-7.631], even adjusting for risk factors (OR 2.794, 95% CI: 1.215-7.460). Logistic regression analysis showed that the dominant genetic model increased the CAD risk (OR 2.313, 95% CI: 1.070-6.983) after adjusting the confounding factors. Meta-analysis results of 13 studies revealed that PCSK9 E670G polymorphism was correlated with CAD risk under different genetic models. CONCLUSION: Our results demonstrated that PCSK9 E670G genotype was associated with a high risk of CAD.

[Photosynthetic gas exchange and water utilization of flag leaf of spring wheat with bunch sowing and field plastic mulching below soil on semi-arid rain-fed area.] / åŠå¹²æ—±åŒºè†œä¸Šè¦†åœŸç©´æ’­å¯¹æ˜¥å°éº¦æ——å¶å ‰åˆä½œç”¨å’Œæ°´åˆ†åˆ©ç”¨çš„å½±å“.

Based on the field experiment which was conducted in Dingxi County of Gansu Province, and involved in the three treatments: (1) plastic mulching on entire land with soil coverage and bunching (PMS), (2) plastic mulching on entire land and bunching (PM), and (3) direct bunching without mulching (CK). The parameters of SPAD values, chlorophyll fluorescence parameters, photosynthetic gas exchange parameters, as well as leaf area index (LAI), yield, evapotranspiration, and water use efficiency in flag leaves of spring wheat were recorded and analyzed from 2012 to 2013 continuously. The results showed that SPAD values of wheat flag leaves increased in PMS by 10.0%-21.5% and 3.2%-21.6% compared to PM and CK in post-flowering stage, respectively. The maximum photochemical efficiency (Fv/Fm) , actual photochemical efficiency (ΦPS2) of photosystem 2 (PS2), and photochemical quenching coefficient (qP) of PMS were higher than those of PM and CK, the maximum increment values were 6.1%, 9.6% and 30.9% as compared with PM, and significant differences were observed in filling stage (P＜0.05). The values of qN in PMS were lowest among the three treatments, and it decreased significantly by 23.8% and 15.4% in heading stage in 2012 and 2013 respectively, as compared with PM. The stoma conductance (gs) of wheat flag leaves in PMS was higher than that of PM and CK, with significant difference being observed in filling stage, and it increased by 17.1% and 21.1% in 2012 and 2013 respectively, as compared with PM. The transpiration rate (Tr), net photosynthetic rate (Pn), and leaf instantaneous water use efficiency (WUEi) except heading stage in 2013 of PMS increased by 5.4%-16.7%, 11.2%-23.7%, and 5.6%-7.2%, respectively, as compared with PM, and significant difference of WUEi was observed in flowering stage in 2012. The leaf area index (LAI) of PMS was higher than that of PM and CK, especially, it differed significantly in seasonal drought of 2013. Consequently, the PMS increased the SPAD values in flag leaves of spring wheat, and the capacity of flag leaves for photo energy assimilation and photosynthetic gas exchange were enhanced, caused more photosynthetic energy flowing into photochemical process, as well as decreased the heat dissipation, resulted in the increment of Pn and WUEi. Based on the higher Pn and LAI, the yield and WUE of PMS increased.

[Pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites in rhesus monkeys].

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.

[Effect of IFN-lambda2 on apoptotic protein in the myocardium in mice with viral myocarditis].

OBJECTIVE: INF-lambda has anti-viral and anti-tumor activities. Its application in viral myocarditis (VMC) has not been reported. This study investigated the role of INF-lambda in acute VMC in mice. METHODS: Forty mice were randomly divided into three groups: VMC (n=15), IFN-lambda2-treated VMC (n=15) and control (n=10). VMC was induced by an intraperitoneal injection of Coxsackievirus B3 (CVB3).The control group was intraperitoneally injected with 2% PBS. The IFN-lambda2-treated VMC group was administered with 400 ng IFN-lambda2 (0.1 mL) by subcutaneous injections daily, for 5 days. The control and the VMC groups were given equal amount of nomal saline.The surviving mice were sacrificed 9 days after IFN-lambda2 treatment. The pathological changes of heart tissues were examined under a light microscope. Bcl-2 and Bax expression in heart tissues was determined by immunohistochemistry. RESULTS: The control group presented normal heart tissues. The INF-lambda2-treated VMC group showed significantly a lower pathological score (1.5+/-0.5) than the untreated VMC group (2.8+/-0.8) (P<0.01). Bcl-2 expression decreased (P<0.01), in contrast, Bax expression increased (P<0.01) in the untreated VMC group compared with that in the control group. INF-lambda2 treatment resulted in an increased Bcl-2 expression (P<0.01) and a decreased Bax expression (P<0.01) compared to the untreated VMC group. CONCLUSIONS: INF-lambda2 may alleviate myocardial injuries and inhibit cardiomyocytic apoptosis, thus providing protective effects on myocardial cells in mice with acute VMC.

[Evolution characteristics of flag leaf photosynthesis and grain yield of wheat cultivars bred in different years].

Taking six winter wheat (Triticum aestivum) cultivars, i. e., 'Wangshuibai' and 'Bima 1' bred in 1950s, 'Zhengyin 1' and 'Yangmai 1' bred in 1970s, and 'Yumai 34' and 'Ningmai 9' bred in 1990s, as test materials, field experiments were conducted to study the evolution characteristics of their flag leaf photosynthesis and grain yield. The results showed that compared with those bred in 1950s and 1970s, the cultivars bred in 1990s had higher chlorophyll content, net photosynthetic rate (Pn), PS II maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency (PhiPSII), photochemical quenching coefficient (qp) and non-photochemical quenching coefficient (qN) at grain-filling stage, their flag leaf had a longer functional duration and senesced slower, and their harvest indices were higher, with the grain yield increased by 25.90% and 11.29%, respectively. It was suggested that in the evolution process of wheat cultivars from 1950s to 1990s, the improved photosynthetic capacity and the lengthened functional duration of flag leaf after anthesis were the key physiological bases for grain yield enhancement.

Morphine suppresses intracellular interferon-alpha expression in neuronal cells.

Interferon alpha (IFN-alpha) not only plays a key role in innate host immunity against infections but also is involved in the cellular functions of the central nervous system (CNS). In this study, we examined the impact of morphine on IFN-alpha expression in human neuronal cells (NT2-N). Similar to human immune cells, NT2-N cells also expressed IFN-alpha at both mRNA and protein levels. IFN-alpha expression in NT2-N cells, however, was inhibited by morphine. Naltrexone antagonized the inhibitory effect of morphine on IFN-alpha expression in NT2-N cells. The specific mu opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7-amide (CTAP), also blocked the morphine action on intracellular IFN-alpha expression. Investigation of the mechanisms involved in the morphine action showed that although morphine had little effect on the expression of key IFN regulatory factors (IRFs), morphine inhibited IFN-alpha promoter activation and suppressed the expression and phosphorylation of signal transducer and activator of transcription 1 (STAT1) in the neuronal cells. These findings provide direct in vitro evidence that opioids may impair neuronal cell-mediated innate protection in the CNS.

Methamphetamine enhances HIV infection of macrophages.

Epidemiological studies have demonstrated that the use of methamphetamine (meth), a sympathomimetic stimulant, is particularly common among patients infected with HIV. However, there is a lack of direct evidence that meth promotes HIV infection of target cells. This study examined whether meth is able to enhance HIV infection of macrophages, the primary target site for the virus. Meth treatment resulted in a significant and dose-dependent increase of HIV reverse transcriptase activity in human blood monocyte-derived macrophages. Dopamine D1 receptor antagonists (SCH23390 and SKF83566) blocked this meth-mediated increase in the HIV infectivity of macrophages. Investigation of the underlying mechanisms of meth action showed that meth up-regulated the expression of the HIV entry co-receptor CCR5 on macrophages. Additionally, meth inhibited the expression of endogenous interferon-alpha and signal transducer and activator of transcription-1 in macrophages. These findings provide direct in vitro evidence to support the possibility that meth may function as a cofactor in the immunopathogenesis of HIV infection and may lead to the future development of innate immunity-based intervention for meth users with HIV infection.

[Effects of Huoxue Qianyang Formula on expressions of proto-oncogenes c-fos and c-myc in spontaneous hypertensive rats with ventricular hypertrophy].

OBJECTIVE: To explore the possible mechanism of Huoxue Qianyang Formula (HXQYF), a compound traditional Chinese herbal medicine, in reversing the left ventricular hypertrophy (LVH) of spontaneous hypertensive rats (SHRs) by analyzing the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle. METHODS: The experimental study was carried out in SHRs, the sex- and age-matched Wistar-Kyoto (WKY) rats were served as normal control (n=5, normal saline 10 ml/kg daily). Twenty-five SHRs were randomly divided into five groups: untreated group (n=5, normal saline 10 ml/kg daily), high-dose HXQYF-treated group (n=5, 0.84 g/ml HXQYF, 10 ml/kg daily), medium-dose HXQYF-treated group (n=5, 0.42 g/ml HXQYF, 10 ml/kg daily), low-dose HXQYF-treated group (n=5, 0.21 g/ml HXQYF, 10 ml/kg daily) and cilazapril-treated group (n=5, 1 mg/ml cilazapril, 10 ml/kg daily). The drugs were intragastrically administered once daily for 14 weeks. The expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were detected separately by in situ hybridization histochemical method and immunohistochemical method. RESULTS: Compared with the normal control group, the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were significantly increased in untreated group (P<0.01). After treatment, the expressions of c-fos and c-myc mRNAs in left ventricular muscle in HXQYF-treated groups were significantly down-regulated as compared with those of the untreated group (P<0.05). The expressions of c-myc protein were also significantly decreased in high- and medium-dose HXQYF-treated groups as compared with the untreated group (P<0.05), but it had no significant effects in protein expression of c-fos in the three HXQYF-treated groups. CONCLUSION: HXQYF can inhibit the expression of c-myc in ventricular hypertrophy tissue, which may be the mechanism in treating LVH of hypertension.

The protective effect of chitin and chitosan against Vibrio alginolyticus in white shrimp Litopenaeus vannamei.

White shrimp, Litopenaeus vannamei, which had been injected with chitin at 4, 6 and 8 microg g(-1) or chitosan at 2, 4 and 6 microg g(-1), were challenged with pathogen Vibrio alginolyticus at 2 x 10(6) colony-forming units (cfu) shrimp(-1) and then placed in seawater of 34 per thousand. The survival of shrimp that received chitin or chitosan at either dose was significantly higher than that of control shrimp after 1 day, and at the termination of the experiment (6 days after the challenge). In another experiment, the total haemocyte count (THC), phenoloxidase activity, respiratory burst, superoxide dismutase (SOD) activity, and phagocytic activity to V. alginolyticus were measured when L. vannamei (10.4 +/- 0.7 g) were injected individually with chitin at 4 and 6 microg g(-1) or chitosan at 2 and 4 microg g(-1). L. vannamei received chitin at 6 microg g(-1) or chitosan at 2 and 4 microg g(-1) increased significantly its THC and respiratory burst after 2 days. L. vannamei received chitin at 6 microg g(-1) or chitosan at 2 and 4 microg g(-1) still maintained significantly higher phenoloxidase activity after 6 days. L. vannamei received chitin at 4 and 6 microg g(-1) or chitosan at 2 and 4 microg g(-1) increased its phagocytic activity against V. alginolyticus after 1 day, respectively. It is therefore concluded that L. vannamei that received chitin at 6 microg g(-1) or chitosan at 4 microg g(-1) or less increased its immune ability and resistance to V. alginolyticus infection.