Repression of the SUMO-conjugating enzyme UBC9 is associated with lowered double minutes and reduced tumor progression.

Double minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DM-carried gene expression in vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition.

Folic acid blocks ferroptosis induced by cerebral ischemia and reperfusion through regulating folate hydrolase transcriptional adaptive program.

Cerebral ischemia-reperfusion (I/R) injury is notably linked with folic acid (FA) deficiency. The aim of our investigation was to explore the effects and underlying mechanisms by which FA mitigates I/R, specifically through regulating the GCPII transcriptional adaptive program. Initially, we discovered that following cerebral I/R, levels of FA, methionine synthase (MTR), and methylenetetrahydrofolate reductase (MTHFR) were decreased, while GCPII expression was elevated. Secondly, administering FA could mitigate cognitive impairment and neuronal damage induced by I/R. Thirdly, the mechanism of FA supplementation involved suppressing the transcriptional factor Sp1, subsequently inhibiting GCPII transcription, reducing Glu content, obstructing cellular ferroptosis, and alleviating cerebral I/R injury. In summary, our data demonstrate that FA affords protection against cerebral I/R injury by inhibiting the GCPII transcriptional adaptive response. These findings unveil that targeting GCPII might be a viable therapeutic strategy for cerebral I/R.

Biomedical association analysis between G2/M checkpoint genes and susceptibility to HIV-1 infection and AIDS progression from a northern chinese MSM population.

BACKGROUND: MSM are at high risk of HIV infection. Previous studies have shown that the cell cycle regulation plays an important role in HIV-1 infection, especially at the G2/M checkpoint. ATR, Chk1, Cdc25C and CDK1 are key genes of G2/M checkpoint. However, the association between SNPs of these genes and susceptibility to HIV-1 infection and AIDS progression remains unknown. METHODS: In this study, 42 tSNPs from the above four G2/M checkpoint genes were genotyped in 529 MSM and 529 control subjects from northern China to analyze this association. RESULTS: The results showed that rs34660854 A and rs75368165 A in ATR gene and rs3756766 A in Cdc25C gene could increase the risk of HIV-1 infection (P = 0.049, OR = 1.234, 95% CI 1.001-1.521; P = 0.020, OR = 1.296, 95% CI 1.042-1.611; P = 0.011, OR = 1.392, 95% CI 1.080-1.794, respectively), while Chk1 rs10893405 (P = 0.029, OR = 1.629, 95% CI 1.051-2.523) were significantly associated with AIDS progression. Besides, rs34660854 (P = 0.019, OR = 1.364, 95% CI 1.052-1.769; P = 0.022, OR = 1.337, 95% CI 1.042-1.716, under Codominant model and Dominant model, respectively) and rs75368165 (P = 0.006, OR = 1.445, 95% CI = 1.114-1.899; P = 0.007, OR = 1.418, 95% CI 1.099-1.831, under Codominant model and Dominant model, respectively) in ATR gene, rs12576279 (P = 0.013, OR = 0.343, 95% CI 0.147-0.800; P = 0.048, OR = 0.437, 95% CI 0.192-0.991, under Codominant model and Dominant model, respectively) and rs540436 (P = 0.012, OR = 1.407, 95% CI 1.077-1.836; P = 0.021, OR = 1.359, 95% CI 1.048-1.762, under Codominant model and Dominant model, respectively) in Chk1 gene, rs3756766 (P = 0.013, OR = 1.455, 95% CI 1.083-1.954; P = 0.009, OR = 1.460, 95% CI 1.098-1.940, under Codominant model and Dominant model, respectively) in Cdc25C gene and rs139245206 (P = 0.022, OR = 5.011, 95% CI 1.267-19.816; P = 0.020, OR = 5.067, 95% CI 1.286-19.970, under Codominant model and Recessive model, respectively) in CDK1 gene were significantly associated with HIV-1 infection under different models. CONCLUSIONS: We found that genetic variants of G2/M checkpoint genes had a molecular influence on the occurrence of HIV-1 infection and AIDS progression in a northern Chinese MSM population.

The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma.

BACKGROUND: Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) on long non-coding RNAs (lncRNAs) that affect competing endogenous RNAs (ceRNA) regulation mechanism with the risk and prognosis of HCC. METHODS: Based on a set of bioinformatics strategies, eight lncRNA genes that affect HCC through the mechanism of lncRNA-mediated ceRNA were systematically screened, and 15 SNPs that affect microRNA (miRNA) binding in these lncRNA genes were annotated. Genotyping was performed in 800 HCC cases and 801 healthy controls to examine associations of these SNPs with HCC in a northeastern Chinese Han population. RESULTS: The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. In addition, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage cancers in a stratified analysis of clinical characteristics. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or AST/ALT ratio in HCC patients. Furthermore, we constructed potential ceRNA regulatory axes that might be affected by five positive SNPs to explain the causes of these genetic associations. CONCLUSIONS: HOTAIR rs7958904, PVT1 rs3931282, rs1134492 and rs10589312, and EGFR-AS1 rs84557 might be predictors for HCC risk or prognosis. Our results provide new insights into how SNPs on lncRNA-mediated ceRNAs confer interindividual differences to occurrence and progression of HCC.

Association of Polymorphisms in NHEJ Pathway Genes with HIV-1 Infection and AIDS Progression in a Northern Chinese MSM Population.

Background and Aims: Men who have sex with men (MSM) are at high risk of HIV infection. The nonhomologous end joining (NHEJ) pathway is the main way of double-stranded DNA break (DSB) repair in the higher eukaryotes and can repair the DSB timely at any time in cell cycle. It is also indicated that the NHEJ pathway is associated with HIV-1 infection since the DSB in host genome DNA occurs in the process of HIV-1 integration. The aim of the present investigation was to evaluate associations of single-nucleotide polymorphisms (SNPs) in NHEJ pathway genes with susceptibility to HIV-1 infection and AIDS progression among MSM residing in northern China. Methods: A total of 481 HIV-1 seropositive men and 493 HIV-1 seronegative men were included in this case-control study. Genotyping of 22 SNPs in NHEJ pathway genes was performed using the SNPscan™ Kit. Results: Positive associations were observed between XRCC6 rs132770 and XRCC4 rs1056503 genotypes and the susceptibility to HIV-1 infection. In gene-gene interaction analysis, significant SNP-SNP interactions of XRCC6 and XRCC4 genetic variations were found to play a potential role in the risk of HIV-1 infection. In stratified analysis, XRCC5 rs16855458 was significantly associated with CD4+ T cell counts in AIDS patients, whereas LIG4 rs1805388 was linked to the clinical phases of AIDS patients. Conclusions: NHEJ gene polymorphisms can be considered to be risk factors of HIV-1 infection and AIDS progression in the northern Chinese MSM population.

Decreased flow-mediated dilation in healthy Chinese adolescent with a family history of type 2 diabetes.

BACKGROUND: Endothelial dysfunction appears early in the development of cardiovascular disease and is associated with type 2 diabetes. We, therefore, tested the hypothesis that endothelial dysfunction is already present in healthy Chinese adolescent participants at risk of type 2 diabetes and associates with physical activity. METHODS: We investigated the flow-mediated dilation in 65 first-degree relatives (normal tension, normal glucose tolerance) and 62 age-, sex- and BMI-matched controls without a family history of type 2 diabetes by ultrasound. Physical activity level was assessed using the Global Physical Activity Questionaire and type 2 diabetes family history through self-reporting. The association between physical activity and flow-mediated dilation was evaluated by Pearson correlations and multiple regressions in adolescents with or without a family history of type 2 diabetes. RESULTS: Female adolescents display better flow-mediated dilation than males. Adolescents with a family history of type 2 diabetes had significantly impaired flow-mediated dilation than healthy controls. Among the parameter detection in the blood, the flow-mediated dilation is only positively associated with high-density lipoprotein cholesterol level, but not others. Interestingly, flow-mediated dilation is positively corrected with physical activity scores in both the male and female adolescents, while slightly impaired but not significant in adolescents with a family history of type 2 diabetes. CONCLUSION: Studies in adolescents are important to understand the early pathogenesis of type 2 diabetes. Findings of this investigation suggest that family history of type 2 diabetes may play a role in regulating the vascular function in Chinese adolescents. Given the impaired flow-mediated dilation in individuals with family history and the effects of physical activity in improved flow-mediated dilation, people with a family history of type 2 diabetes may need higher physical activity levels to attenuate their susceptibility to impaired flow-mediated dilation.

Association of APEX1 and XRCC1 Gene Polymorphisms With HIV-1 Infection Susceptibility and AIDS Progression in a Northern Chinese MSM Population.

Background: Some studies have shown that the base excision repair (BER) pathway has an effect on HIV-1 replication. APEX1 and XRCC1 as key BER genes may affect DNA repair capacity. However, the roles of single nucleotide polymorphisms (SNPs) in APEX1 and XRCC1 and their impact on HIV-1 infection and AIDS progression remain unclear. Methods: A custom-designed 48-Plex SNPscan Kit was used for detection of single nucleotide polymorphisms. 601 HIV-1-infected men who have sex with men (MSM) and 624 age-matched healthy individuals were recruited in northern China. Four SNPs (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 gene and three SNPs (rs1001581, rs25487 and rs25489) in XRCC1 gene were genotyped. The generalized multifactor dimension reduction (GMDR) method was used to identify the SNP-SNP interactions. Results: In this study, rs1130409 G allele, rs1001581 C allele and rs25487 C allele were associated with a higher risk of HIV-1 infection susceptibility (p = 0.020, p = 0.007 and p = 0.032, respectively). The frequencies of APEX1 haplotype TT and XRCC1 haplotype CT showed significant differences between cases and controls (p = 0.0372 and p = 0.0189, respectively). Interestingly, stratified analysis showed that the frequency of rs1001581 C allele was significantly higher in AIDS patients with the CD4+ T-lymphocyte count <200 cells/µl than those with >200 cells/µl (p = 0.022). Moreover, significant gene-gene interactions among rs1130409, rs1001581 and rs25487 were identified by GMDR (p = 0.0107). Specially, individuals with five to six risk alleles have a higher susceptibility to HIV-1 infection than those with zero to two risk alleles (p < 0.001). Conclusion: APEX1 and XRCC1 gene polymorphisms were associated with the susceptibility to HIV-1 infection and AIDS progression in MSM populations in northern China.

Protective effects of physical activity in colon cancer and underlying mechanisms: A review of epidemiological and biological evidence.

Numerous epidemiological studies indicate that physical activity has a protective effect against colon cancer development and progression. Further, the relevant biological mechanisms where physical activity or exercise may improve survival have also been initially examined. In this review, we provide an overview of the epidemiological evidence to date which comprises 16 cohort studies of the effects of physical activity on colon cancer outcomes including cancer recurrence, cancer-specific and overall survival. Moreover, we present four potential mechanisms involving shear pressure, systemic milieu alteration, extracellular vesicles, and immune function by which physical activity and exercise may favorably impact colon cancer. Research currently in progress will provide definitive evidence of survival benefits resulting from exercise and future work will help clarify the role of targeted exercise and the relevant mechanisms involved.

Association Between Nonsyndromic Cleft Lip and Palate and 2 Polymorphic Loci: A Meta-Analysis.

OBJECTIVES: The relationship between Noggin (NOG) and methylenetetrahydrofolate reductase and nonsyndromic cleft lip and palate (NSCLP) has been reported participate in craniofacial development but need further evidence. To indicate the susceptibility between the 2 genes and NSCLP, rs227731 and rs1801131 polymorphisms were included in the present research. This research may provide some genetic clues for disease detection and surveillance. DESIGN: Seventeen studies including 4023 cases and 5691 controls were provided for meta-analysis, and odds ratio (OR) with 95% CI were obtained to estimate NSCLP risk. RESULTS: Our analysis suggested potential association of rs227731C on increasing the risk of NSCLP in the Caucasian group and total group but not Asian group under all models: allele (OR = 1.45, 95% CI = 1.21-1.75, P < .0001), homozygote (OR = 2.03, 95% CI = 1.42-2.90, P < .0001), heterozygote (OR = 1.44, 95% CI = 1.19-1.73, P = .0001), dominant (OR = 1.61, 95% CI = 1.27-2.04, P < .0001), and recessive models (OR = 1.63, 95% CI = 1.25-2.12, P = .0003). Besides, increased risk is related to rs1801131 in Asian group under 3 models: allele (OR = 1.24, 95% CI = 1.06-1.44, P = .006), heterozygote (OR = 1.24, 95% CI = 1.02-1.52, P = .03), and dominant models (OR = 1.29, 95% CI = 1.06-1.56, P = .009). CONCLUSIONS: Our analysis indicates polymorphisms rs227731 and rs1801131 are associated with NSCLP, with predominance of different ethnic group and deepen understanding of NSCLP.

Effect of Thermal Extraction on Coal-Based Activated Carbon for Methane Decomposition to Hydrogen.

After coal is treated by thermal solution of solvent, a certain amount of thermal solution oil and residue can be obtained, and the macromolecular network structure in coal can also be relaxed. These will inevitably affect the emission of harmful gases and distribution of the pore structure when the residue is made into activated carbon (AC). In this paper, the effects of thermal solution pretreatment on the microcrystalline structure, surface properties, pore structure of resultant ACs at different temperatures, and their catalytic performances in methane decomposition to hydrogen were investigated. The results show that the surface oxygen-containing functional groups of the residue-based ACs are changed, and the specific area of ACs increases from 1730 to 2652 m2/g with the increase in activated temperature. The pore diameter distribution of ACs also is changed. In the process of methane decomposition to hydrogen, the residue-based ACs show higher catalytic activity than coal-based ACs. AC-1123-1 and AC-1123 show the best stability, while AC-823-1 has the highest initial activity. With the increase in activated temperature, residue-based ACs show higher activity and stability, and partial fibrous carbon is deposited on the surface of ACs after the reaction. It is thought that increased mesoporosity is beneficial to the catalytic activity and stability of AC in methane decomposition to hydrogen, and the reduction of surface oxygen-containing functional groups contribute to the formation of fibrous carbon on the surface of AC after the reaction.

Association between polymorphisms in MRE11 and HIV-1 susceptibility and AIDS progression in a northern Chinese MSM population.

BACKGROUND: Previous studies reported that DNA damage repair (DDR) genes may play an important role in HIV-1 infection. The MRE11 gene, a member of the MRN complex, plays an essential part in the homologous recombination pathway, which is one of the classical DDR pathways. Previous reports have demonstrated that MRE11 has an effect on HIV-1 replication. However, the role of SNPs in the MRE11 gene and their impact on HIV-1 infection and AIDS progression remain unknown. METHODS: In this study, 434 MSM HIV-1-infected patients in northern China and 431 age-matched healthy controls were enrolled. Five SNPs (rs2155209, rs10831234, rs13447720, rs601341 and rs11020803) at the MRE11 gene were genotyped. Another series of cases (409 MSM HIV-1-infected patients) and controls (403 age-matched healthy males) were recruited as the validation set. RESULTS: In our study, rs10831234 showed differences in allele frequencies between cases and controls (P = 0.005). Additionally, there was an association between rs10831234 and HIV-1 infection susceptibility in dominant and additive models (P = 0.005 and P = 0.006, respectively). All significant associations were replicated in the validation set, and the associations were still significant after Bonferroni correction for multiple testing when the two data sets were combined. Furthermore, in haplotype association analyses between the case and control groups, the frequencies of the haplotypes Crs11020803Crs10831234 and Trs11020803Trs10831234 showed significant differences (P = 0.0181 and P = 0.0068, respectively). CONCLUSIONS: We demonstrated that the MRE11 rs10831234-T allele may confer increased risk of HIV-1 infection.

Associations between PTPN2 gene polymorphisms and psoriasis in Northeastern China.

Psoriasis is a chronic immune-mediated disease with a complex etiology involving various genetic and immunological factors as well as environmental factors. Psoriasis is thought to be mediated by T-cells polarized to a Th17 fate. PTPN2 encodes the T-cell protein tyrosine phosphatase, which acts as a negative regulator of the JAK/STAT signaling pathways downstream of cytokines and plays a prominent role in T-cell activation, signaling and/or effector function. To evaluate the association between PTPN2 gene polymorphisms and psoriasis in the Northeastern Chinese population. A case-control study was conducted, and 398 patients with psoriasis and 397 healthy controls were genotyped for thirteen genetic polymorphisms in PTPN2. Allele analysis revealed that rs2847297, rs657555 and rs482160 polymorphisms were significantly associated with psoriasis (p = 0.0018, p = 0.0017 and p = 0.0086, respectively). Genotype analysis also revealed that these polymorphisms were significantly associated with psoriasis under different models (codominant, dominant and recessive models) (p < 0.05). In this study, three haplotypes (H1, H7 and H11) were also found to be associated with psoriasis (p = 0.0015, p = 0.0094, and p = 0.0124, respectively). These results indicate that PTPN2 genetic polymorphisms are associated with psoriasis in the Northeastern Chinese population.

COX-2 expression in ovarian cancer: an updated meta-analysis.

The prognostic role of COX-2 expression in ovarian cancer patients has been studied for years, while results remain controversial. Thus we performed a meta-analysis to evaluate the prognostic impact of COX-2 expression on survival of ovarian cancer patients. The databases PubMed, Embase and CNKI were searched. Summary hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to analyze the correlations between COX-2 expression and overall survival (OS), and disease-free survival (DFS). A total of 1,867 patients from 18 studies were enrolled in the final analysis. The results showed that patients with higher COX-2 expression had a poor OS (HR: 1.48; 95% CI: 1.19-1.85) and DFS (HR: 1.81, 95% CI: 1.28-2.55). Subgroup analysis showed that there had significant associations between COX-2 expression and survival rate in most of the subgroups. Furthermore, there were significant associations between COX-2 expression and several clinical parameters such as FIGO stage, histological type and age. These results showed the patients with higher COX-2 expression had a significantly poorer survival rate, COX-2 expression had the potential to be a prognostic marker of ovarian cancer.

Association between the BRCA2 rs144848 polymorphism and cancer susceptibility: a meta-analysis.

The BRCA2 gene plays an important role in cancer carcinogenesis, and polymorphisms in this gene have been associated with cancer risk. The BRCA2 rs144848 polymorphism has been associated with several cancers, but results have been inconsistent. In the present study, a meta-analysis was performed to assess the association between the rs144848 polymorphism and cancer risk. Literature was searched from the databases of PubMed, Embase and Google Scholar before April 2016. The fixed or random effects model was used to calculate pooled odd ratios on the basis of heterogeneity. Meta-regression, sensitivity analysis, subgroup analysis and publication bias assessment were also performed using STATA 11.0 software according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009. A total of 40 relevant studies from 30 publications including 34,911 cases and 48,329 controls were included in the final meta-analysis. Among them, 22 studies focused on breast cancer, seven on ovarian cancer, five on non-Hodgkin lymphoma, and the remaining six studies examined various other cancers. The meta-analysis results showed that there were significant associations between the rs144848 polymorphism and cancer risk in all genetic models. Stratified by cancer type, the rs144848 polymorphism was associated with non-Hodgkin lymphoma. Stratified by study design, the allele model was associated with breast cancer risk in population-based studies. The meta-analysis suggests that the BRCA2 rs144848 polymorphism may play a role in cancer risk. Further well-designed studies are warranted to confirm these results.

Association of single nucleotide polymorphisms of APOBEC3G with susceptibility to HIV-1 infection and disease progression among men engaging in homosexual activity in northern China.

Men who have sex with men (MSM) are at high risk of HIV infection. The APOBEC3G (apolipoprotein B mRNA editing catalytic polypeptide 3G) protein is a component of innate antiviral immunity that inhibits HIV-1 replication. In the present study, a total of 483 HIV-1 seropositive men and 493 HIV-1 seronegative men were selected to investigate the association between single nucleotide polymorphisms (SNPs) of the APOBEC3G gene and susceptibility to HIV-1 infection and AIDS progression among MSM residing in northern China. Genotyping of four SNPs (rs5757465, rs3736685, rs8177832, and rs2899313) of the APOBEC3G was performed using the SNPscan™ Kit, while the rs2294367 polymorphism was genotyped using the SNaPshot multiplex system. Our results disclosed no association between the SNPs of APOBEC3G and susceptibility to HIV-1, or effects of these polymorphisms on the CD4+ T cell count or clinical phase of disease. A meta-analysis of 1624 men with HIV-1 infection and 1523 controls suggested that the association between rs8177832 and susceptibility was not significant. However, we observed a trend towards association with HIV-1 infection for haplotype TTACA (p = 0.082). The potential role of variants of APOBEC3G in HIV-1/AIDS warrants further investigation.

The polymorphisms of MSH6 gene are associated with AIDS progression in a northern Chinese population.

It has been reported that DNA repair genes play an important role in HIV-1 infection and AIDS progression. One DNA repair pathway, the mismatch repair (MMR) is associated with a wide variety of tumors. However, the role of single nucleotide polymorphisms (SNPs) in the MMR genes and their importance in HIV-1 infection and AIDS progression remain unclear. In the present study, 479 HIV-1-infected and 487 healthy individuals from northern China were genotyped for nine SNPs in the MSH2 gene (rs13019654, rs4608577, rs4952887, rs6726691, rs10191478, rs12999145, rs1981929, rs2042649, rs2303428) and five SNPs in the MSH6 gene (rs2348244, rs3136245, rs3136329, rs2072447, rs7562048). Our results showed that the rs7562048 G allele frequency was significantly higher in the cases with the CD4(+) T-lymphocyte count <200cells/µl than those with >200cells/µl (P=0.001, OR=1.811, 95% CI 1.255-2.614), which is in agreement with the result of the Bonferroni correction. The frequencies of the rs2348244 C allele and rs3136245 T allele were higher in the cases at clinical phase IV than those at clinical phase I+II+III (P=0.026, OR=1.591, 95% CI 1.056-2.398 and P=0.019, OR=1.749, 95% CI 1.096-2.791, respectively); however, this difference is not supported by the Bonferroni correction. There were no significant differences in the frequency of allele, genotype and haplotype of the 14 SNPs between HIV-1-infected individuals and healthy controls (P>0.05). These results suggest that the rs7562048 is associated with the clinical features and that the MSH6 gene polymorphisms likely play an important role in the progression of AIDS in the northern Chinese population.

Associations between two single-nucleotide polymorphisms (rs1801278 and rs2943641) of insulin receptor substrate 1 gene and type 2 diabetes susceptibility: a meta-analysis.

The objective of the study is to assess the association between rs1801278 and rs2943641 of insulin receptor substrate 1 gene (IRS1) and the susceptibility to type 2 diabetes. A literature search strategy was conducted to identify all references lists of relevant studies. The fixed or random effect model was used to calculate the pooled ORs on the basis of heterogeneity. Further analyses were performed to explore the sources of heterogeneity by sensitivity analysis, meta-regression analysis, and subgroup analysis. There was significant association between rs1801278 and type 2 diabetes risk in recessive model (AA vs. GA + GG, p = 0.043) and codominant model (AA vs. GG, p = 0.007). Subgroup analysis showed that the association between rs1801278 and type 2 diabetes risk was significant in dominant model (GA + AA vs. GG, p = 0.044), codominant model (GA vs. GG, p = 0.039), codominant model (AA vs. GG, p = 0.044), overdominant model (GG + AA vs. GA, p = 0.037) in Asian and codominant model (AA vs. GG, p = 0.039) in Caucasian of rs1801278. The association between rs2943641 and type 2 diabetes risk was significant in codominant model (CT vs. CC, p = 0.023) in Caucasian. This meta-analysis suggests that rs1801278 may play a role in type 2 diabetes risk, especially in Asian. It also indicates that rs2943641 may be associated with type 2 diabetes risk in Caucasian. Further larger studies should be performed to warrant confirmation.

Baicalin alleviates diabetes­associated cognitive deficits via modulation of mitogen-activated protein kinase signaling, brain­derived neurotrophic factor and apoptosis.

Baicalin is an important active component of the medicinal herb Scutellaria baicalensis Georgi and has shown a variety of pharmacological actions. The present study aimed to evaluate the neuroprotective effects of baicalin against diabetes­associated cognitive deficits (DACD) in rats and to elucidate the potential molecular mechanisms of action. A rat model of diabetes mellitus was prepared by intraperitoneal injection of streptozotocin. After the successful establishment of the diabetic rat model, baicalin (50, 100 and 200 mg/kg) or vehicle was administrated for seven weeks. Learning and memory function were assessed using the Morris water maze test. At the end of the experiment, the activities of acetylcholinesterase (AChE) and choline acetylase (ChAT) were determined using commercial kits. Furthermore, the expression of proteins involved in mitogen­activated protein kinase (MAPK) cascades [extracellular signal­regulated kinase (ERK), c­Jun N­terminal kinase (JNK) and p38], brain­derived neurotrophic factor (BDNF) and apoptosis­associated proteins [caspase­3, B-cell lymphoma 2 (Bcl­2) and Bcl-2-associated X protein (Bax)] were detected by western blot analysis. Caspase­3 activity was also analyzed using a commercial kit. The results demonstrated that diabetic rats exhibited decreases in body weight, decreases in the percentage of time spent in the target quadrant and the number of times of crossing the platform in the water maze test, as well as decreases in neuronal survival, ChAT, phosphorylated (p)ERK, BDNF and Bcl­2. Furthermore, diabetic rats showed increases in escape latency and mean path length in the water maze test, increases in the levels of hippocampal AChE, p­JNK, p­p38, caspase­3 and Bax as well as plasma glucose. However, in diabetic rats treated with baicalin, all of the abovementioned observations were obviously reversed. The findings suggested that baicalin exerts neuroprotective effects against DACD via modulation of MAPK cascades, BDNF and apoptosis.

A haplotype in the CCR5 gene promoter was associated with the susceptibility to HIV-1 infection in a northern Chinese population.

It has been reported that single nucleotide polymorphisms (SNPs) in the promoter of the CCR5 gene are associated with the risk for HIV-1 infection and AIDS progression. Using resequencing, we performed a systematic survey of 78 HIV-1 seropositive individuals and 70 population-matched healthy control individuals from northern China to investigate SNPs of the CCR5 gene promoter and evaluated their effects on HIV-1 infection and the progression of AIDS. Linkage disequilibrium (LD) plots and haplotypes were generated using Haploview software. The association analyses were statistically compared using the Chi-square test with SPSS13.0 software for Windows. Seven SNPs (58755A>G, 58791C>T, 58934G>T, 59029A>G, 59353C>T, 59402A>G and 59653C>T) in the region of the CCR5 gene promoter were evaluated in this study. Among the seven SNPs, the minor allele frequencies of 58755G and 58791T were less than 2%. The differences in frequencies of the other five SNPs were not significant between case and control cohorts (P>0.05). In the case cohort, the association between these SNPs and clinical features (CD4+ T-lymphocyte counts and clinical categories) was not significant (P>0.05); however, there was a significant association between the haplotype GGTAC and susceptibility to HIV-1 infection (P<0.05), which is not consistent with other reports studied in different populations. The results suggest that the haplotype GGTAC may have a role in the process of HIV-1 infection in the northern Chinese population.

XRCC3 Thr241Met polymorphism with lung cancer and bladder cancer: a meta-analysis.

Several studies have investigated the associations between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and the susceptibility to lung cancer and bladder cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 22 case control studies, including 2976 cases and 4495 controls for lung cancer, and 3445 cases and 4599 controls for bladder cancer, met the inclusion criteria and were selected. Overall, there was no evidence showing a significant association between XRCC3 Thr241Met polymorphism and lung cancer risk. Furthermore, the results for bladder cancer showed that significant decreased risk was found for the additive model (odds ratio [OR] = 0.959, 95% confidence interval [CI], 0.924-0.996) and dominant model (OR = 0.982, 95% CI, 0.963-1.000) but not for the recessive model (OR = 0.958, 95% CI, 0.905-1.014). In summary, our meta-analysis indicates that XRCC3 Thr241Met polymorphism may be weakly associated with the risk of bladder cancer. (Cancer Sci 2010).