Effect of vitamin supplementation on polycystic ovary syndrome and key pathways implicated in its development:A Mendelian randomization study

BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in reducing the risk of PCOS remains a subject of debate.AIM To investigate the impact of plasma levels of vitamins A,B12,D,E,and K on PCOS and key pathways implicated in its development,namely,insulin resistance,hyperlipidemia,and obesity,through Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies.The primary analysis was performed using the random-effects inverse-variance-weighted approach.Complementary analyses were conducted using the weighted median,MR-Egger,MR-robust adjusted profile score,and MR-PRESSO approaches.RESULTS The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E(odds ratio[OR]=0.118;95%confidence interval[CI]:0.071–0.226;P<0.001)and vitamin B12(OR=0.753,95%CI:0.568–0.998,P=0.048).An association was observed between vitamin E levels and insulin resistance(OR=0.977,95%CI:0.976–0.978,P<0.001).Additionally,genetically predicted higher concentrations of vitamins E,D,and A were suggested to be associated with a decreased risk of hyperlipidemia.Increased vitamins K and B12 levels were linked to a lower obesity risk(OR=0.917,95%CI:0.848–0.992,P=0.031).CONCLUSION The findings of this MR study suggest a causal relationship between increased vitamins A,D,E,K,and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.

Identification of key genes involved in post-traumatic stress disorder:Evidence from bioinformatics analysis

BACKGROUND Post-traumatic stress disorder(PTSD)is a serious stress-related disorder.AIM To identify the key genes and pathways to uncover the potential mechanisms of PTSD using bioinformatics methods.METHODS Gene expression profiles were obtained from the Gene Expression Omnibus database.The differentially expressed genes(DEGs)were identified by using GEO2R.Gene functional annotation and pathway enrichment were then conducted.The gene-pathway network was constructed with Cytoscape software.Quantitative real-time polymerase chain reaction(qRT-PCR)analysis was applied for validation,and text mining by Coremine Medical was used to confirm the connections among genes and pathways.RESULTS We identified 973 DEGs including 358 upregulated genes and 615 downregulated genes in PTSD.A group of centrality hub genes and significantly enriched pathways(MAPK,Ras,and ErbB signaling pathways)were identified by using gene functional assignment and enrichment analyses.Six genes(KRAS,EGFR,NFKB1,FGF12,PRKCA,and RAF1)were selected to validate using qRT-PCR.The results of text mining further confirmed the correlation among hub genes and the enriched pathways.It indicated that these altered genes displayed functional roles in PTSD via these pathways,which might serve as key signatures in the pathogenesis of PTSD.CONCLUSION The current study identified a panel of candidate genes and important pathways,which might help us deepen our understanding of the underlying mechanism of PTSD at the molecular level.However,further studies are warranted to discover the critical regulatory mechanism of these genes via relevant pathways in PTSD.

Literature-based knowledgebase of pancreatic cancer gene to prioritize the key genes and pathways

Pancreatic cancer （PC） occurs when malignant cells develop in the part of the pancreas, a glandular organ behind the stomach. For 2015, there are about 40,560 people dead of pancreatic cancer （20,710 men and 19,850 women） in the US （Siegel et al., 2015）. Though PC accounts for about 3% of all cancers in the US, it can cause about 7% of cancer deaths. This is mainly because that the early stages of this cancer do not usually produce symptoms, and thus the cancer is almost always fatal when it is diagnosed.

Mitogen-activated protein kinase signal pathways play an important role in right ventricular hypertrophy of tetralogy of Fallot

Background Tetralogy of Fallot （TOF） is the most common malformation of children with an incidence of approximately 10% of congenital heart disease patients. There can be a wide spectrum to the severity of the anatomic defects, which include ventricular septal defect, aortic override, right ventricular outflow tract obstruction, and right ventricular hypertrophy. We examined the relationship between right ventricular hypertrophy in patients with TOF and the gene expression of factors in the mitogen-activated protein kinase （MAPK） signal pathway. Methods To gain insight into the characteristic gene（s） involved in molecular mechanisms of right ventricular hypertrophy in TOF, differential mRNA and micro RNA expression profiles were assessed using expression-based micro array technology on right ventricular biopsies from young TOF patients who underwent primary correction and on normal heart tissue. We then analyzed the gene expression of the MAPK signal pathway using reverse transcription-polymerase chain reaction （RT-PCR） in normals and TOF patients. Results Using the micro RNA chip V3.0 and human whole genome oligonucleotide microarray VI.0 to detect the gene expression, we found 1068 genes showing altered expression of at least two-fold in TOF patients compared to the normal hearts, and 47 micro RNAs that showed a significant difference of at least two-fold in TOF patients. We then analyzed these mRNAs and micro RNAs by target gene predicting software Microcosm Targets version 5.0, and determined those mRNA highly relevant to the right ventricular hypertrophy by RT-PCR method. There were obvious differences in the gene expression of factors in the MAPK signal pathway when using RT-PCR, which was consistent to the results of the cDNA microarray.Conclusion The upregulation of genes in the MAPK signal pathway may be the key events that contribute to right ventricular hypertrophy and stunted angiogenesis in patients with TOF.