Comparative description of haplotype structure and genetic diversity of MDR1 (ABCB1) in HIV-positive and HIV-negative populations

Human P-glycoprotein (P-gp), encoded by MDR1 (ABCB1), is an efflux transporter with a wide specificity for substrates/drugs, including HIV protease inhibitors which are commonly used in HIV/AIDS treatment. Three single nucleotide polymorphisms (SNPs) in MDR1 have been shown to affect P-gp expression and function, and may affect HIV/AIDS treatment outcome: 1236C>T [G412G, exon-12], 2677G>T/A [A893S/T, exon-21] and 3435C>T [I1145I, exon-26]. In the present study, our aims were (i) to compare the 3-SNP MDR1 haplotype structure and genetic diversity between North American HIV-positive and HIV-negative individuals belonging to four major ethnic groups and (ii) to determine whether the haplotype structure and genetic diversity observed in these ethnically admixed populations differ from that in ethnically non-admixed populations. For these aims, we analyzed a cohort of 447 HIV/AIDS patients (White [n = 193], Black [n = 235], Hispanic [n = 17], and Asian [n = 2]). Results obtained for these patients were compared with the results for (i) HIV-negative individuals (n = 356) and (ii) various HapMap and Environmental Genome Project populations. We observed that the genetic characteristics of MDR1 were largely consistent between HIV-positive and HIV-negative populations, but there were striking interethnic differences in the genetic characteristics of MDR1 in both populations. Although it appeared that the genetic characteristics of MDR1 were largely consistent between ethnically admixed and non-admixed populations, genetic characterization of the admixed populations remains to be done. Thus, our results provide useful comparative insights about the genetic characteristics of MDR1 that could be extrapolated across population groups worldwide. For a meaningful interpretation of these results regarding HIV/AIDS treatment outcome, MDR1 haplotype/diplotype structure data, genetic characterization of population admixture, and polymorphisms in other relevant drug transporter and/or metabolizing enzyme genes should be considered in future clinical studies.     

Expression of Von Willebrand factor in normal and diseased rat livers and in cultivated liver cells

Von Willebrand factor (vWf) is an adhesive glycoprotein known to play an important role in hemostasis and in tissue injury. Because the latter process resembles hepatic fibrogenesis, we studied the tissue distribution of vWf in diseased livers. In normal rat liver vWf was strongly expressed in the vascular endothelium and as small spots or fiber-like structures in the hepatic parenchyma. During acute liver injury, pronounced staining was observed within the area of necrosis. In fibrotic livers vWf deposits were distributed predominantly at the scar-parenchyma interface but also within the septum and in sinusoidal lining cells. Testing different liver cell populations in vitro demonstrated that vWf gene expression was limited to endothelial cells (ECs) and, therefore, the latter cell population might represent the vWf-positive cells detected in vivo. The distribution of vWf within fibrotic septa suggests that vWf becomes a component of the extracellular matrix (ECM) in fibrotic livers.     

IL-6/JAK2/STAT3对口腔鳞状细胞癌生物学行为的影响

目的 观察白细胞介素6抗体(IL-6)/蛋白酪氨酸激酶2抗体(JAK2)/信号传导和转录激活因子3抗体(STAT3)对口腔鳞状细胞癌(简称口腔鳞癌)细胞生物学行为的影响.方法 对口腔鳞癌细胞系进行慢病毒转染敲低IL-6基因,设立两组对照,一组为未干预组,另一组为空白载体组.通过CCK8实验和克隆形成实验检测IL-6对口...     

Gammaaminobutyric Acid A Receptor Alpha 3 Subunit is Overexpressed in Lung Cancer

The identification of tumor-associated antigens, which are specifically expressed in cancer tissues, is very important for immunotherapy of lung cancer. We have combined the in silico screening and experimental verifying to identify genes that are differently expressed in cancers compared with their corresponding normal tissues. Using these methods, we have identified that GABRA3 gene was overexpressed in lung cancer and rarely expressed in other cancers. Furthermore, GABRA3 protein expression was significantly higher in the lower grade of lung cancer. It may compose functional GABA-gated channel with other subunits. This study demonstrated GABRA3 could be a potential biomarker for diagnosis of lung cancer, and GABAA receptors may play an important role in cancer differentiation.     

The implications of obesity on pregnancy

Obesity is a modern day epidemic. The incidence appears to be rapidly increasing in both developed and developing countries and has become much more obvious in the last decade. It is regarded as one of the major risk factors in pregnant women and has particularly gained recognition in obstetric practice due to its potentially adverse effects on pregnancy and the fetus.There is evidence to show that obesity in pregnancy contributes to increased morbidity and mortality in both mother and baby. It is associated with adverse outcomes such as preeclampsia, gestational diabetes, thromboembolism, fetal abnormalities and large for gestational infants. According to the Confidential Enquiries into Maternal Deaths in the United Kingdom, 35% of the women who died had a BMI of 30 or more. All these issues highlight the immense importance in treating women with obesity in maternity practice accordingly.     

Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18

Prophylactic vaccination against HPV 16 and 18 has the potential for effective prevention of high-grade precancer (cervical intraepithelial neoplasia [CIN)] 2/3) and ICC caused by these viruses (globally 50 and 70%, respectively) when employed in women prior to starting sexual activity. To provide data for decisions on HPV vaccination in China, we determined HPV type-distribution in ICC and CIN 2/3 from women of different regions within China. A multicenter study was conducted by randomized sampling of paraffin blocks of 664 ICC (630 squamous cell carcinoma [SCC]; 34 adenocarcinoma [ADC]), 569 CIN 2/3 cases from seven regions of China. Histological diagnosis was confirmed in 1,233 cases by consensus review. HPV DNA was detected using the SPF10 LiPA25 version 1 assay. HPV prevalence was 97.6% in SCC, 85.3% in adenocarcinoma, and 98.9% in CIN 2/3. HPV 16 (76.7%) and HPV 18 (7.8%) were the most common, together accounting for 84.5% of SCC, followed by HPV 31 (3.2%), HPV 52 (2.2%), and HPV 58 (2.2%). HPV positivity in SCC did not differ notably by region. However, SCC cases from women ≤34 years had higher HPV 16 positivity than women over 50 years, among whom HPV 52, 58, and 39 were more common. HPV 16 and 18 were under-represented, whereas HPV 31, 52, and 58 were over-represented in CIN2/3 compared to SCC. The potential impact of vaccines against oncogenic HPV types 16 and 18 is estimated to be high (84.5%) against total SCC. These data are critical for China’s future evaluation of the cost-effectiveness of current cervical cancer vaccines and of HPV-based screening guidelines.