Lishan Wang

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations.

Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including −3279T>G and −3156G>A in the enhancer region, (TA)6>7 in the TATA box, and 211G>A (G71R), 686C>A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of −3279T>G, (TA)6>7, 211G>A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the −3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (−3279G; −3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.

Semiconducting single-walled carbon nanotubes synthesized by S-doping

An approach was presented for synthesis of semiconducting single-walled carbon nanotubes (SWNTs) by sulfur (S) doping with the method of graphite arc discharge. Raman spectroscopy, UV-vis-NIR absorption spectroscopy and electronic properties measurements indicated the semconducting properties of the SWNTs samples. Simulant calculation indicated that S doping could induce convertion of metallic SWNTs into semiconducting ones. This strategy may pave a way for the direct synthesis of pure semiconducting SWNTs.

Family-based association studies of CAPON and schizophrenia in the Chinese Han population.

Although there is evidence pointing to CAPON as a susceptible gene for schizophrenia, the results of independent association studies have so far been inconsistent. A recent case-control study by Zheng et al. supported CAPON as a susceptible site for the disease in the Chinese Han population. In their study both the single polymorphism (rs348624) and individual haplotypes showed significant association with schizophrenia. Our study further investigates this relationship this time using a family-based association. We selected 5 SNPs including rs348624 and performed a Transmission Disequilibrium Test (TDT) in 319 Chinese Han trios. Our results identified no single marker nor haplotype associated with schizophrenia, which did not suggest that CAPON was a susceptible site in the Chinese Han population, or it appeared unlikely that the CAPON played a major role in the aetiology of schizophrenia. Since there is consistent evidence pointing to 1q21-22 as a positional candidate region for schizophrenia, we suggest that further research should focus on other genes located in this region.

Association of CYP2A6*4 with Susceptibility of Lung Cancer: A Meta-Analysis

Objectives To assess the association between the variant of Cytochrome P450 2A6 whole gene deletion (CYP2A6*4) polymorphism and risk of lung cancer. Methods Two investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library and Chinese National Knowledge Infrastructure (CNKI). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP2A6*4 and lung cancer were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Results This meta-analysis included seven eligible studies, which included 2524 lung cancer cases and 2258 controls (cancer–free). Overall, CYP2A6*4 was associated with the risk of lung cancer (allele*4 vs. allele non-*4, pooled OR u200a=u200a0.826, 95% CI u200a=u200a0.725−0.941, P-value u200a=u200a0.004). When stratifying for population, significant association was observed in Asian (additive model, pooled OR u200a=u200a0.794, 95% CI u200a=u200a0.694−0.909, P-value u200a=u200a0.001; dominant model, pooled OR u200a=u200a0.827, 95% CI u200a=u200a0.709−0.965, P-value u200a=u200a0.016; recessive model (pooled OR u200a=u200a0.444, 95% CI u200a=u200a0.293−0.675, P-value <0.0001). In the overall analysis, a comparably significant decrease in the frequency of *4/*4 genotype was detected between cases and controls in Asian while no *4/*4 genotype was detected in Caucasian in collected data. Conclusion This meta-analysis suggests that the CYP2A6*4 polymorphism is associated with susceptibility of lung cancer in Asian. The whole gene deletion of CYP2A6 may decrease the risk of lung cancer in Asian samples.

Dynamic Network of Transcription and Pathway Crosstalk to Reveal Molecular Mechanism of MGd-Treated Human Lung Cancer Cells

Recent research has revealed various molecular markers in lung cancer. However, the organizational principles underlying their genetic regulatory networks still await investigation. Here we performed Network Component Analysis (NCA) and Pathway Crosstalk Analysis (PCA) to construct a regulatory network in human lung cancer (A549) cells which were treated with 50 uM motexafin gadolinium (MGd), a metal cation-containing chemotherapeutic drug for 4, 12, and 24 hours. We identified a set of key TFs, known target genes for these TFs, and signaling pathways involved in regulatory networks. Our work showed that putative interactions between these TFs (such as ESR1/Sp1, E2F1/Sp1, c-MYC-ESR, Smad3/c-Myc, and NFKB1/RELA), between TFs and their target genes (such as BMP41/Est1, TSC2/Myc, APE1/Sp1/p53, RARA/HOXA1, and SP1/USF2), and between signaling pathways (such as PPAR signaling pathway and Adipocytokines signaling pathway). These results will provide insights into the regulatory mechanism of MGd-treated human lung cancer cells.

Exploration of inhibitory mechanisms of curcumin in lung cancer metastasis using a miRNA- transcription factor-target gene network

The present study was aimed to unravel the inhibitory mechanisms of curcumin for lung cancer metastasis via constructing a miRNA-transcription factor (TF)-target gene network. Differentially expressed miRNAs between human high-metastatic non-small cell lung cancer 95D cells treated with and without curcumin were identified using a TaqMan human miRNA array followed by real-time PCR, out of which, the top 6 miRNAs (miR-302b-3p, miR-335-5p, miR-338-3p, miR-34c-5p, miR-29c-3p and miR-34a-35p) with more verified target genes and TFs than other miRNAs as confirmed by a literature review were selected for further analysis. The miRecords database was utilized to predict the target genes of these 6 miRNAs, TFs of which were identified based on the TRANSFAC database. The findings of the above procedure were used to construct a miRNA-TF-target gene network, among which miR-34a-5p, miR-34c-5p and miR-302b-3p seemed to regulate CCND1, WNT1 and MYC to be involved in Wnt signaling pathway through the LEF1 transcription factor. Therefore, we suggest miR-34a-5p/miR-34c-5p/miR-302b-3p —LEF1—CCND1/WNT1/MYC axis may be a crucial mechanism in inhibition of lung cancer metastasis by curcumin.

Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC) with each other based on microarray dataset.

AbstractLiver carcinomas have been classified into three types: hepatocellular carcinoman (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC). We aim to find the commonn and different characteristic of these three types of liver cancer. The genen expression profiling of HCC, CC, and CHC were compared with each other, andn enrichment pathways and processes in these three liver cancers were also identified.n Using GSE15765 datasets downloaded from NCBI GEO database, the gene expressionn profiling of HCC, CC, and CHC were compared with each other (HCC compared with CC,n HCC compared with CHC, and CC compared with HCC). Then, the differentially expressedn genes (DEGs) were identified in these three groups respectively, and three PPIn networks were constructed for DEGs in each group. Subsequently, the clusters inn these networks were identified and further analyzed by ClusterONE and MCODE.n Finally, gene set enrichment analysis enrichment analysis was performed ton illustrate altered pathways and processes for each type of liver cancer. A total ofn 112, 530, and 64 DEGs were identified in three groups, respectively, and three PPIn networks were constructed respectively for the corresponding group. Through then cluster analysis, we found some new differential marker genes for distinguishing then difference between these three types of liver cancer. We also indicated that we cann distinguish HCC with CC through altered pathways and processes. Our findings developn new biomarkers for categorizing the primary liver cancer and may improve patientn prognosis of these cancers. However, further validation is required since ourn results were based on microarray data derived from a small sample size.

Vitamin D Receptor, an Important Transcription Factor Associated with Aldosterone-Producing Adenoma

Objective To explore the endocrine mechanisms of aldosterone-producing adenoma (APA) by using the microarray expression profiles of normal and APA samples. Methods The gene expression profile GSE8514 was downloaded from Gene Expression Omnibus database, including samples from normal adrenals (n = 5) and APAs (n = 10). The differentially expressed genes (DEGs) were identified by samr package and endocrine DEGs were obtained according to Clinical Genome Database. Then, functional enrichment analysis of screened DEGs was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery). Finally, a regulatory network was constructed to screen endocrine genes related with adrenal dysfunction and pathway enrichment analysis for the constructed network was performed. Results A total of 2149 DEGs were identified including 379 up- and 1770 down-regulated genes. And 26 endocrine genes were filtered from the DEGs. Furthermore, the down-regulated DEGs are mainly related to protein kinase cascade, response to molecule of bacterial origin, response to lipopolysaccharide, cellular macromolecule catabolic process and macromolecule catabolic process, while the up-regulated DEGs are related with regulation of ion transport. The target genes of VDR (vitamin D receptor), one of the three endocrine genes differentially expressed in the regulatory network, were endocrine genes including CYP24A1 (25-hydroxyvitamin D-24-hydroxylase) and PTH (parathyroid hormone). Three pathways may be associated with APA pathogenesis including cytokine-cytokine receptor interaction, pathways in cancer and autoimmune thyroid disease. Conclusion The VDR is the most significant transcription factor and related endocrine genes might play important roles in the endocrine mechanisms of APA.

Retraction Note to: Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC) with each other based on microarray dataset

The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

Drug-Eluting Stents for Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials

Background Drug-eluting stents (DES) are increasingly used for treatment of acute coronary syndrome (ACS). However, clinical efficacy and safety of various types of DES is not well established in these subjects. We therefore evaluated clinical utility of second-generation and first-generation DES in patients with ACS by conducting a meta-analysis. Methods A search of Medline, Embase, the Cochrane databases, and Web of Science was made. Randomized controlled trials (RCTs) which compared second-generation DES (everolimus-eluting stents [EES] or zotarolimus-eluting stents [ZES]) versus first-generation DES (sirolimus-eluting stents [SES] or paclitaxe-eluting stents [PES]) in patients with ACS and provided data on clinical efficacy or safety endpoints were included. Pooled estimates were calculated using random-effects model. Result A total of 2,757 participants with ACS in 6 RCTs were included. Compared with first-generation one, second-generation DES trended to be associated with the decreased incidence of definite or probable stent thrombosis in ACS patients (risk ratio [RR] u200a=u200a0.60, 95% confidence intervals [CI] 0.33 to 1.07, pu200a=u200a0.09). However, the rate of target lesion revascularization (TLR) significantly increased in second-generation DES (RRu200a=u200a2.08, 95%CI 1.25 to 3.47, pu200a=u200a0.005). There were no significant differences in the incidence of major adverse cardiac events (MACEs), all-cause death, cardiac death, and recurrent myocardial infarction between the two arms (all p>0.10). The second-generation EES showed a tendency towards lower risk of MACEs (pu200a=u200a0.06) and a beneficial effect on reducing stent thrombosis episodes (pu200a=u200a0.009), while the second-generation ZES presented an increased occurrence of MACEs (pu200a=u200a0.02) and TLR (pu200a=u200a0.003). Conclusion Second-generation DES, especially EES, appeared to present a lower risk of stent thrombosis, whereas second-generation ZES might increase the need for repeat revascularization in ACS patients. During coronary interventional therapy, DES class should be adequately considered in order to maximize clinical benefit of DES implantation in these specific subjects.