NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation.

Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-κB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-α, IL-6, IL-1ß, and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-κB nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-α, IL-6, IL-1ß, and MCP-1 overproduction, mTOR upregulation, and NF-κB nuclear translocation. The PROMO software analysis indicated NF-κB binding site in the -1643 to -1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-κB promoted the transcription of miR-99a by binding to the -1643 to -1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-κB on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-κB signal. NF-κB promoted miR-99a production by binding to the -1643 to -1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis.

Meta-Analysis of miR-146a Polymorphisms Association with Coronary Artery Diseases and Ischemic Stroke.

Coronary artery disease (CAD) and ischemic stroke (IS) are manifestations of atherosclerosis, with a high death rate. miR-146a is a microRNA that participates in the progress of CAD and IS. A single nucleotide polymorphism (SNP) in the precursor of miR-146a, rs2910164, was found to be associated with the risks of CAD and IS. However, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the relationship of rs2910164 and CAD as well as IS susceptibility. The database Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM) were searched for related studies. Crude odds ratios with 95% confidence intervals were used to investigate the strength of the association by random- or fixed-effect model. A total of eight studies, with 3138 cases and 3097 controls were identified for the meta-analysis. The results shows that rs2910164 is associated with the risk of CAD significantly in allelic model (OR = 0.86), homozygous model (OR = 0.70), heterozygous model (OR = 0.80) and dominant model (OR = 0.76). The subjects carrying the GG genotype, GG + GC genotype or G allele are at lower risks of CAD. For the susceptibility of IS, there are no significant associations between rs2910164 and total studies. However, in subgroup analysis by sample size and ethnicity, the GG, GG + GC and G allele of rs2910164 are found to be associated with higher risks of IS in large sample size group and in Koreans, under homozygous and dominant models. In conclusion, the current meta-analysis suggests lower risks of CAD for GG, GG + GC genotype and G allele of rs2910164, while rs2910164 is not associated with the risk of IS. Thus rs2910164 might be recommended as a predictor for susceptibility of CAD, but not IS.

Meta-analysis of the association between MBOAT7 rs641738, TM6SF2 rs58542926 and nonalcoholic fatty liver disease susceptibility.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a kind of liver disease caused by factors other than excessive alcohol use. It is the leading cause of liver injury in developed countries. The membrane-bound O-acyltransferase 7 (MBOAT7) and transmembrane 6 superfamily member 2 (TM6SF2) are associated with lipid metabolism. Studies found a mutation on MBOAT7, rs641738 and another on TM6SF2, rs58542926 were associated with liver diseases, including NAFLD. However, the results were inconclusive and inconsistent. METHODS: In the present meta-analysis, the databases Pubmed, Embase, Chinese National Knowledge Infrastructure, and Chinse Biomedical Literature Database were searched for related studies. The deadline of publications was July 10th, 2018. The data from included studies were extracted by 2 independent investigators. STATA 12.0 software was used in the present meta-analysis. RESULTS: A total of 9 papers with 20 studies, including 5415 cases and 17896 controls were identified for the meta-analysis. The results indicated lower risks of NAFLD for CC genotype of TM6SF2 rs58542926 in homozygous, heterozygous, dominant and recessive models (CC vs. TT: OR = 0.33; CC vs. CT: OR = 0.58; CC vs. CT + TT: OR = 0.64; CC + CT vs. TT: OR = 0.32). These decreased risks of NAFLD also existed in Asians in all genetic models except allelic model, and in Caucasians in the heterozygous model (CC vs. CT, OR = 0.52) and the dominant model (CC + CT vs. TT, OR = 0.50). No association existed between MBOAT7 rs641738 and NAFLD risks in all genetic models (CC vs. TT: OR = 0.91; CC vs. CT: OR = 0.96; CC vs. CT + TT: OR = 0.95; CC + CT vs. TT: OR = 0.91; C vs. T: OR = 0.99). CONCLUSION: CC genotype of TM6SF2 rs58542926 was associated with a significantly lower risk of NAFLD, while MBOAT7 rs641738 was not related to NAFLD risks.

Meta-Analysis for the Association between Polymorphisms in Interleukin-17A and Risk of Coronary Artery Disease.

Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias among study designs.

Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in the aortas of ApoE(-/-) mice.

Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide, and has become the leading cause of death. The present study was designed to investigate the impact of high-fat diet on ApoE(-/-) mice exhibiting atherosclerosis by detecting the genome-wide expression profile of lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were identified (≥2.0 folds). Simultaneously, 357 differentially expressed mRNAs from the same chip were found. The expression differences of lncRNAs and mRNAs were consistent in both qPCR and microarray detection. Annotation results of the mRNAs which correlated with lncRNAs showed that the commonly related pathways were metabolism and inflammation. Hypergeometric distribution analysis indicated that the differentially expressed lncRNAs had been mostly regulated by transcription factors (TFs) such as Myod1, Rxra, Pparg, Tcf3, etc. Additional lncRNA-target-TFs network analysis was conducted for the top 20 differentially expressed lncRNAs. The results indicated Hnf4a, Ppara, Vdr, and Runx3 as the TFs most likely to regulate the production of these lncRNAs, and might play roles in inflammatory and metabolic processes in atherosclerosis. In a nutshell, the present study identified a panel of dysregulated lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related atherogenesis.

[Molecule biology study on the effective bacteria in ANAMMOX sludge].

A greater understanding of anaerobic ammonium oxidation bacteria will help to pave the way for the new biological nitrogen removal process application in practice. To this end, this study used molecule biology methods. Crude DNA of the total bacteria in a cultivated sludge with ANAMMOX capability was extracted and purified. Then PCR amplification using specific primers, clone and sequencing processes were performed. The partial 16S rDNA sequence of cultivated ANAMMOX bacteria is 836bp. Some clones have one to two base mutation(s). Phylogenetic analysis indicates that the cultivated ANAMMOX bacteria in this study close to Candidatus Brocadia anammoxidans, anaerobic ammonium-oxidizing Planctomycete and uncultured anoxic sludge bacterium KUI with the same function, whereas the cultivated ANAMMOX bacteria are relatively low DNA sequence similarity to the forementioned bacteria using alignment analysis. The results suggest that there is a kind of bacterium which has never been found before with ANAMMOX capability existing in nature.

Clinicopathological Significance of DLC-1 Expression in Cancer: a Meta-Analysis.

BACKGROUND: Recent reports have shown that DLC-1 is widely expressed in normal tissues and is down- regulated in a wide range of human tumors, suggesting it may act as a tumor suppressor gene. We conducted a meta-analysis to determine the correlation between DLC-1 expression and clinicopathological characteristics in cancers. MATERIALS AND METHODS: A detailed literature search was made for relevant publications from PubMed, EMBASE, Cochrane library databases, Web of Science, CNKI. The methodological quality of the studies was also evaluated. Analyses of pooled data were performed and odds ratios (ORs) were calculated and summarized. RESULTS: Final analysis was performed of 1,815 cancer patients from 19 eligible studies. We observed that DLC- 1 expression was significantly lower in cancers than in normal tissues. DLC-1 expression was not found to be associated with tumor differentiation status. However, DLC-1 expression was obviously lower in advance stage than in early-stage cancers and was more down-regulated in metastatic than non-metastatic cancers. CONCLUSIONS: The results of our meta-analysis suggested that DLC-1 expression is significantly lower in cancers than in normal tissues. Aberrant DLC-1 expression may play an important role in cancer genesis and metastasis.

A Meta-Analysis of the Association between Polymorphisms in MicroRNAs and Risk of Ischemic Stroke.

Ischemic stroke (IS) is responsible for a high death rate and for adult disability worldwide. MiR-146a (rs2910164), miR-149 (rs2292832), miR-196a2 (rs11614913) and miR-499 (rs3746444) are found to be associated with ischemic stroke. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the four polymorphisms and IS risk. The databases Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched for related studies. A total of five studies including 2230 cases and 2229 controls were identified for the meta-analysis. The results indicate that TT genotype and T allele of miR-149 (rs2292832) are associated with significantly lower risks of IS in a homozygous model (OR = 0.70) and an allelic model (OR = 0.86). No significant associations were found between miR-146a (rs2910164), miR-196a2 (rs11614913), miR-499 (3746444) and IS susceptibility in any of the studies. However, subgroup analysis by sample size indicates a significant decrease in risks of IS for CC genotype and C allele of miR-146a (rs2910164) in the large sample size group. Therefore, miR-149 (rs2292832) might be recommended as a predictor for IS risk, while miR-146a (rs2910164), miR-196a2 (rs11614913), miR-499 (3746444) are not.

Meta-analysis of six randomized control trials of chemotherapy plus anti-HER monoclonal antibody for advanced gastric and gastroesophageal cancer.

BACKGROUND: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti- HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six randomized phase II/III trials. MATERIALS AND METHODS: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. RESULTS: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publication bias for all endpoints. CONCLUSIONS: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.