NUCB2 polymorphisms are associated with an increased risk for type 2 diabetes in the Chinese population.

BACKGROUND: The nucleobindin 2 (NUCB2) gene encodes the NUCB2 protein, which plays a critical role in glucose metabolism and diabetes. This study explored the correlation between NUCB2 genetic variants and type 2 diabetes mellitus (T2DM). The study further examined the different NUCB2 variants that confer risk to T2DM in Chinese Han populations. METHODS: This study evaluated the anthropometric and glycemic profiles of 578 T2DM patients and 1,609 healthy controls. Subsequently, we genotyped five single nucleotide polymorphisms (SNPs) (rs10832756, rs1330, rs10766383, rs10832757, and rs11024251) in all the study participants using a Sequenom Mass ARRAY SNP genotyping platform. RESULTS: The distribution of polymorphisms was significantly different between the T2DM patients and healthy controls. Our logistic regression analysis results showed that the five NUCB2 SNPs are significantly correlated with the risk for T2DM, especially rs11024251(P=2.97×10-6). Interestingly, analysis of male and female sub-populations separately showed that only two of the SNPs (rs10832757 and rs11024251) have significant correlation to T2DM in males [P=0.0244, odds ratio (OR) 1.28 and P=0.0062, OR 1.35, respectively). In females however, we identified four significant SNPs (rs1330, rs10766383, rs10832757, and rs11024251; P<0.05, OR 1.31-1.42). Furthermore, we found that rs1330 is associated with body mass index of female subpopulation only (P=0.0174, ß =0.0060). CONCLUSIONS: NUCB2 polymorphisms could have a pivotal role in the presence of T2DM. Sex-specific SNPs of NUCB2 could account for the differences in clinical features of T2DM between male and female subpopulations. Nevertheless, our results should be replicated using larger sample sizes, and experimental investigations are needed to elucidate the molecular mechanisms of the associations observed in this study.

Charactering the metabolism of cryptotanshinone by human P450 enzymes and uridine diphosphate glucuronosyltransferases in vitro.

Cryptotanshinone (CT) is the main active component in the root of Salvia miltiorrhiza Bunge (SMB) that displays antibacterial, anti-inflammatory and anticancer activities. In this study, we characterized phase I and phase II metabolism of CT in human liver microsomes in vitro and identified the metabolic enzymes (CYPs and UGTs) involved. The metabolites of CT generated by CYPs were detected using LC-MS/MS and the CYP subtypes involved in the metabolic reactions were identified using chemical inhibitors of CYP enzymes and recombinant human CYP enzymes (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Glucuronidation of CT was also examined, and the UGT subtypes involved in the metabolic reactions were identified using recombinant human UGT enzymes (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15 and 2B17). After adding NADPH to the human liver microsomes incubation system, CT was transformed into 6 main dehydrogenation and hydroxylation metabolites. CYP2A6, CYP3A4 and CYP2C19 were the major contributors to the transformation of its hydroxylation metabolites. CYP2C19, CYP1A2 and CYP3A4 were the major contributors to the transformation of its hydrogenation metabolites in human liver microsomes. This study showed that the metabolites at m/z of 473 were mediated by UGT1A9 and that the metabolites at m/z of 489 were mediated by UGT2B7 and UGT2B4. CT was extensively metabolized by UGTs following metabolism by CYPs in the liver.

[Seroepidemiological survey of Toxoplasma gondii in dogs in Urumqi].

From 2011 to 2012 in Urumqi, blood samples of 308 household dogs and of 110 stray dogs were collected from three pet hospitals and a stray dog shelter, respectively. Serum anti-Toxoplasma gondii IgG was detected by ELISA. The results showed that the overall seropositive rate was 31.8% (133/418). The rate in household dogs and stray dogs was 29.9% (92/308) and 37.3% (41/110), respectively (P>0.05). Among 308 household dogs, the positive rate in males and females was 27.0% (41/152) and 32.7% (51/156), respectively (P>0.05). The seropositive rate in dogs <1 years old, 1-2 years old, and more than 2 years old was 27.1% (32/118), 30.2% (29/96), and 33.3% (31/94), respectively (P>0.05). The results revealed a high seroprevalence of T. gondii infection in dogs in Urumqi.

[Inhibition of HPV16 E6 oncogene in cervical cancer by RNA interference].

OBJECTIVE: The efficiency of HPV16 E6 gene silenced by RNA interference in vitro and in vivo was assessed. METHODS: The specific siRNA of HPV16 E6 was designed and transfected into CaSki cells by liposome. Cell apoptotic rates and the changes in HPV16 E6 mRNA and protein before and after transfection were measured. Cervical cancer nude mice models were set up, siRNA was injected directly into subcutaneous tumor. The function of siRNA was evaluated by the changes in tumor volume, HPV16 E6 protein expression and apoptosis of tumor cells. RESULTS: In vitro research, the cell apoptotic rates were 7.7%, 11.8%, 37.4% and 12.6% respectively at 24 h, 48 h, 5th day and 9th day after transfection. The HPV16 E6 mRNA was reduced by 77%, 83%, 59% and 41% at 24 h, 48 h, 5th day and 9th day after transfection. The inhibition rates of E6 protein measured by Flow cytometry were 79.7%, 80.4%, 71.3% and 57.4% at 24 h, 48 h, 5th day and 9th day after transfection, which were confirmed by the results of Western blot. In vivo research, E6 siRNA administration groups had great power in inhibiting tumor growth, restraining E6 protein expression, increasing tumor necrosis and apoptosis. The result of repeated injections of siRNA was better than that of single injection. CONCLUSION: RNA interference with HPV16 E6 is specific and highly efficient in vitro and in vivo.

[Relationship between the reduction of FHIT expression and the development of cervical carcinoma].

OBJECTIVE: To explore the relationship between reduction of FHIT expression of fragile histidine triad (FHIT) and the development of cervical carcinoma. METHODS: Expression of the FHIT product was detected by immunohistochemistry in 22 normal cervices and 35 cervical intra-epithelial neoplasias (CINs) as well as 60 primary invasive cervical carcinomas. RESULTS: The rates for loss or reduction of expression of FHIT protein in the squamous epithelium of normal cervices, CIN I-II, CIN III and noninvasive carcinoma and invasive cervical carcinoma were 0% (0/22), 20% (4/20), 53.3% (8/15), 81.7% (49/60) respectively (P<0.05). Among the well differentiated, intermediately differentiated and poorly differentiated invasive cervical carcinoma, the rates for loss or reduction of expression of FHIT protein were 60.0% (6/10), 70.0% (14/20), and 96.7% (29/30) respectively (P<0.05). The rate of the impaired FHIT protein expression in the invasive cervical carcinoma with lymph node metastasis (90.9%) was higher than that without lymph node metastasis (79.6%). CONCLUSION: The impaired FHIT protein expression might be a useful indicator in identifying the possibility of the progression of advanced CINs into invasive cervical carcinoma. FHIT protein expression might indicate the clinical characteristic of cervical carcinoma cells and the prognosis of cervical carcinoma.

[Study on the influence of medical abortion and surgical abortion on subsequent pregnancy].

OBJECTIVE: To evaluate and compare medical abortion versus surgical abortion in respect of their influence on the safety of the mother and baby in the subsequent pregnancy and parturition. METHODS: Based on the principle of informed consent of subjects, 150 healthy pregnant women with a past history of having experienced medical abortion once were included in the study group (also called medical abortion group), and in the same period, 150 healthy pregnant women with a past history of having experienced surgical abortion once were enrolled into the comparison group (also called surgical abortion group). From then on, all the pregnant women in the two groups were followed up till a week after labor. The baseline data of the two groups were comparable (P>0.05). The rates of complications observed in these women during pregnancy and labor were evaluated. RESULTS: The incidence rates of miscarriage, placental abnormality, premature delivery and postpartum hemorrhage in the study group were significantly lower than those in the comparison group (P<0.05). No significant differences on other variables were observed between the two groups. CONCLUSION: Medical abortion is probably safer than surgical abortion in respect of their influence on subsequent pregnancy. So, provided there is less contraindication, medical abortion may be the choice for terminating unwanted pregnancy, especially for those women without a child.