Comprehensive research on the distribution of HLA-DRB1 in Chinese populations.

By presenting antigen peptides, HLA-DRB1 plays an important role in the immune system. However, the allele frequency of HLA-DRB1 exon 2 across China has not been comprehensively studied, especially in minority populations. We sampled 3757 individuals from 59 population. The HLA-DRB1 region from 212 to 463 bp (NM_002124.4 exon 2) in each population was sequenced by Sanger sequencing and genotyped via SBTengine® software, and the allele frequency was calculated by GenAlEx 6.5. Eighty-two DRB1 alleles were identified. The expected heterozygosity of DRB1 was lower in the south than in the north, which was inconsistent with the Y chromosome and mitochondrial DNA results. The Mantel test and nonparametric correlation analysis showed that the correlations of the genetic distance with geographical distance and of DRB1 allele frequencies with latitude weakened after the southern and northern groups were considered separately. Principal coordinate analysis showed that populations speaking the same languages were not codistributed. Compared with other genetic markers, the distribution of DRB1 seems less affected by geographic distance and ethnic origin. Local factors such as gene flow with neighbouring populations, geographic isolation or natural selection are important forces shaping the DRB1 gene pool of local populations.

Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.

BACKGROUND: Although the genetic factors associated with hypertension remain unknown, genetic variations in genes related to ion channels, inflammation, and the cell cycle may affect susceptibility to hypertension. In the present study, the association between hypertension and 10 candidate single-nucleotide polymorphisms (SNPs) was evaluated among Chinese Dai people, who have a smaller gene pool than Han individuals. METHODS: A total of 1,193 samples from Dai people were collected, including 488 with hypertension and 705 with normal blood pressure. Based on the preliminary results of whole-genome sequencing among pools of individuals (Pool-seq), 10 candidate SNPs in 6 genes (FAM110D, ADD1, RAG1, CACNA1C, CACNA1A, and NLRP12) were genotyped in the case and control groups by multiplex PCR for SNP genotyping with next-generation sequencing (MultiPCR-NGS). The relationship between hypertension and each candidate SNP was evaluated using the χ 2 test and multiple logistic regression analysis. RESULTS: The χ 2 test showed that the allele frequencies of rs3748856 in FAM110D, rs139118504 in CACNA1A, and rs34436714 in NLRP12 were significantly different between the case and control groups (P < 0.005). After adjusting for age, body mass index, total cholesterol, triglyceride, and low-density lipoprotein, logistic regression analyses revealed that the association between the 3 SNPs and hypertension among Dai people remained significant (P = 0.012, 2.71 × 10-4, and 0.017, respectively). CONCLUSIONS: These findings indicate that there may be different molecular pathogeneses of hypertension among Dai people, which should be noted in future studies.

Association between gene polymorphisms of voltage-dependent Ca2+ channels and hypertension in the Dai people of China: a case-control study.

BACKGROUND: Abnormal calcium homeostasis related to the development of hypertension. As the key regulator of intracellular calcium concentration, voltage-dependent calcium channels (VDCCs), the variations in these genes may have important effects on the development of hypertension. Here we evaluate VDCCs variability with respect to hypertension in the Dai ethnic group of China. METHODS: A total of 1034 samples from Dai individuals were collected, of which 495 were used as cases, and 539 were used as controls. Blood pressure was measured using a standard mercury measurement method, three times with a rest for 5 min, and the average was used for analyses. Seventeen single nucleotide polymorphisms (SNPs) in the four protein-coding genes (CACNA1A, CACNA1C, CACNA1S, CACNB2) of VDCCs were identified by multiplex PCR-SNP typing technique. Chi-square tests and regression models were used to analyse the associations of SNPs with hypertension. RESULTS: The results of chi-square tests showed that the allele frequencies of 5 SNPs were significantly different between the case and the control groups (P < 0.05), but the statistical significance was lost after Bonferroni's correction. However, after adjusting for BMI, age, sex and other factors by logistic regression analyses, the results showed that 5 SNPs consistent with chi-square tests (rs2365293, rs17539088, rs16917217, rs61839222 and rs10425859) were still statistically positive. CONCLUSIONS: This finding suggested that the significant association of these SNPs with hypertension may be noteworthy in future studies.

Meta-analysis of randomized controlled trials of 4 weeks or longer suggest that curcumin may afford some protection against oxidative stress.

Oxidative stress (OS) is associated with aging and multiple diseases, yet the effects of curcumin in humans are not definite. We undertook a meta-analysis of the effects of curcumin on OS biomarkers. In January 2018, we searched PubMed, Books@Ovid, Journals@Ovid, EMBASE, MEDLINE(R), and Web of Science to identify randomized controlled trials conducted ≥4 weeks and investigating the effects of curcumin on OS biomarkers, including glutathione peroxidase (GPX) activity in red blood cells (RBC), serum malondialdehyde (MDA) concentrations, and superoxide dismutase (SOD) activity. The standardized mean difference (SMD) with a 95% confidence interval (CI) was used to present the results. The meta-analysis included eight clinical studies (626 patients). There was a significant reduction in circulating MDA concentrations (SMD = -0.769, 95% CI: -1.059 to -0.478) and a significant increase in SOD activity (SMD = 1.084, 95% CI: 0.487 to 1.680) following curcumin supplementation. There was no change in the GPX activity in RBC. There was no significant association between the MDA-lowering effect of curcumin with underlying diseases or treatment duration. However, curcumin showed the MDA-lowering effect at curcuminoids doses ≥600 mg/d (P < .0001). This effect was greater when combined with piperine than curcuminoids alone (SMD = -1.085, 95% CI: -1.357 to -0.813; SMD = -0.850, 95% CI: -1.158 to -0.542). Curcumin may play an anti-oxidative role by reducing circulating MDA concentrations and increasing SOD activity. Further research of curcumin in different populations with multiple biomarkers of redox status is required.

Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials.

BACKGROUND: Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD). METHODS: A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect. RESULTS: The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = -0.340, 95% confidence interval [CI]: -0.530 to -0.150, P < 0.0001) and TG (SMD = -0.214, 95% CI: -0.369 to -0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = -0.934, 95% CI: -1.289 to -0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = -0.584, 95% CI: -0.980 to -0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies. CONCLUSIONS: Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.

Molecular mechanism of C-reaction protein in promoting migration and invasion of hepatocellular carcinoma cells in vitro.

Hepatocellular carcinoma (HCC) is one of most common malignant cancers and is the second leading cause of cancer related deaths. The prognosis and survival of patients are closely related to the degree of tumor metastasis. The mechanism of HCC metastasis is still unclear. In the present study, we investigated the molecular mechanism of C-reaction protein in promoting migration and invasion of hepatocellular carcinoma cells in vitro. We estimated that CRP is overexpressed in liver cancer tissues and that it promotes invasion and metastasis of HCC in vitro. In the present study, we employed iTRAQ-based mass spectrometry to analyze the HepG2 secretory proteins of CRP siRNA-treated cells and negative control siRNA-treated cells. We identified 109 differentially expressed proteins after silencing CRP, of which 45 were upregulated and 64 were downregulated. Some of the differentially expressed proteins were confirmed by western blot analysis and real-time quantitative PCR. Furthermore, we found that knockdown of CRP substantially abrogates HIF-1α expression levels, the luciferase activity of HIF-1α and ERK and Akt phosphorylation in HepG2 cells. The present study provides a novel mechanism by which CRP promotes the proliferation, migration, invasion and metastasis of hepatocellular carcinoma cells. Inhibition of CRP suppressed migration, invasion and healing of hepatoma carcinoma cells by decreasing HIF-1α activity and CTSD.

Inhibition of FASN suppresses migration, invasion and growth in hepatoma carcinoma cells by deregulating the HIF-1α/IGFBP1 pathway.

Hepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Due to a high propensity to metastasize, active angiogenesis and rapid proliferation, recurrence and poor prognosis are major obstacles for treatment and cure of this disease. However, the detailed mechanisms of how fatty acid synthase (FASN) promotes migration, invasion and healing in tumor cells remain unclear. In the present study, the previous results that FASN was expressed higher in cancer samples than in non-cancerous samples, and influenced migration, invasion of hepatoma carcinoma cells, were verified by immunohistochemistry, tissue microarrays, Transwell assay and wound healing assay. The secretory proteins of hepatocellular carcinoma cells with or without FASN knockdown were analyzed using the isobaric tags for relative and absolute quantitation (iTRAQ) method to identify differentially expressed proteins (DEPs). The DEPs were verified by RT-PCR and western blot analysis, and were consistent with the iTRAQ results. Inhibition of FASN can decrease the levels of IGFBP1, and the expression, activity, and ubiquitination of HIF-1α. Inhibition of FASN can suppress migration, invasion and healing of hepatoma carcinoma cells by decreasing HIF-1α, and IGFBP1.

The dynamics behavior of Rh nanoclusters on boron nitride sheet.

The configurations and corresponding adsorption energies of Rh(n) (n = 4-13) nanoclusters on the boron nitride sheet are investigated by density functional theory (DFT). We use the force-matching method (FMM) to modify parameters of Morse and Tersoff potential functions. To elucidate the dynamical behaviors of Rh nanoclusters on the boron nitride sheet, molecular dynamics (MD) is applied with modified Morse potential function parameter. Finally, the square displacement (SD) is utilized the dynamics behavior of different size Rh nanoclusters at different temperatures.