Cancer is a worldwide epidemic and represents a major threat to human health and survival. Reactive oxygen species (ROS) play a dual role in cancer cells, which includes both promoting and inhibiting ...carcinogenesis. Tea remains one of the most prevalent beverages consumed due in part to its anti- or pro-oxidative properties. The active compounds in tea, particularly tea polyphenols, can directly or indirectly scavenge ROS to reduce oncogenesis and cancerometastasis. Interestingly, the excessive levels of ROS induced by consuming tea could induce programmed cell death (PCD) or non-PCD of cancer cells. On the basis of illustrating the relationship between ROS and cancer, the current review discusses the composition and efficacy of tea including the redox-relative (including anti-oxidative and pro-oxidative activity) mechanisms and their role along with other components in preventing and treating cancer. This information will highlight the basis for the clinical utilization of tea extracts in the prevention or treatment of cancer in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Genome wide association studies (GWASs) have identified tens of thousands of single nucleotide polymorphisms (SNPs) associated with human diseases and characteristics. A significant fraction of GWAS ...findings can be false positives. The gold standard for true positives is an independent validation. The goal of this study was to identify SNP features associated with validation success. Summary statistics from the Catalog of Published GWASs were used in the analysis. Since our goal was an analysis of reproducibility, we focused on the diseases/phenotypes targeted by at least 10 GWASs. GWASs were arranged in discovery-validation pairs based on the time of publication, with the discovery GWAS published before validation. We used four definitions of the validation success that differ by stringency. Associations of SNP features with validation success were consistent across the definitions. The strongest predictor of SNP validation was the level of statistical significance in the discovery GWAS. The magnitude of the effect size was associated with validation success in a non-linear manner. SNPs with risk allele frequencies in the range 30–70% showed a higher validation success rate compared to rarer or more common SNPs. Missense, 5’UTR, stop gained, and SNPs located in transcription factor binding sites had a higher validation success rate compared to intergenic, intronic and synonymous SNPs. There was a positive association between validation success and the level of evolutionary conservation of the sites. In addition, validation success was higher when discovery and validation GWASs targeted the same ethnicity. All predictors of validation success remained significant in a multivariate logistic regression model indicating their independent contribution. To conclude, we identified SNP features predicting validation success of GWAS hits. These features can be used to select SNPs for validation and downstream functional studies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Osteosarcoma (OS) is an aggressive malignant tumor that is mesenchymal in origin with a very low 5-year survival rate, particularly in the patients with locally advanced or metastatic tumors and ...recurrent disease. MicroRNAs (miRNAs) play a critical role in essential biological processes as cellular proliferation, differentiation and apoptosis in normal or cancer cells, including OS cells. In the present study, we aimed to investigate the role of miR-422a in OS. We demonstrated that miR-422a expression was significantly downregulated in OS tissues and cell lines compared with the normal controls. In addition, overexpression of miR-422a was able to inhibit cell proliferation and the ability of invasion, and enhance paclitaxel and cisplatin-mediated apoptosis in OS cells. Inversely, downregulation of miR-422a exhibited an opposite role. We further demonstrated that miR-422a directly targeted TGFβ2 and regulated its expression and the activation of downstream molecules, smad2 and smad3 in OS cells. Thus, miR-422a/TGFβ2/smad axis may be a potential target for OS treatment.
The most obvious pathological characterization of inflammatory bowel disease (IBD) is intestinal epithelium erosion and severe inflammation invasion. Micro-ribonucleic acids (miRNA or microRNA), ...single-stranded noncoding RNAs of ~22 nucleotides, have been considered as the potential therapeutic targets in the pathogenesis of IBD. Many previous studies have focused on the mechanisms that miRNAs use to regulate inflammation, immunity, and microorganisms in IBD. The review highlights in detail the findings of miRNAs in the intestinal epithelial barrier of IBD, and focuses on their gene targets, signaling pathways associated with IBD, and some potential therapies. It will be beneficial for the elucidation of the interaction between miRNAs and the intestinal epithelial barrier in IBD and provide a theoretical reference for preventing and treating IBD in the future.
To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and ...discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP ...levels.
We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P<2.9×10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained ≈5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease.
We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.
Background
Adolescence is a critical period for bone development, and peak bone mass may be reached in late adolescence. Boosting bone accumulation at this time can help preserve adult bone health ...and avoid osteoporosis later in life. Body mass index (BMI) has been found to have a favorable impact on bone mineral density (BMD) in previous research. However, excessive obesity is harmful to health and may lead to various systemic diseases. Therefore, finding an appropriate BMI to maintain a balance between obesity and BMD is critical for adolescents.
Methods
The datasets from the National Health and Nutrition Examination Survey (NHANES) 2011–2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between BMI and BMD. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Subgroup analyses were then conducted based on gender and age.
Results
This population-based study included a total of 6,143 adolescents aged 8–19 years. In a multivariate linear regression analysis, a good association between BMI and total BMD was shown 0.014 (0.013, 0.014). This positive association was maintained in all subgroup analyses grouped by sex and age. Furthermore, the association between BMI and BMD was nonlinear with a saturation point present, as evidenced by smoothed curve fitting. According to the threshold effect study, with an age group of two years, adolescents of different ages had different BMI saturation values with respect to BMD.
Conclusions
Our study showed a significant positive and saturated association between BMI and BMD in adolescents aged 8–19 years. Maintaining BMI at saturation values may reduce other adverse effects while achieving optimal BMD.
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs ...within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Clinically, attention-deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impulsivity, and inattention and is among the most common childhood disorders. These same traits that ...define ADHD are variable in the general population, and the clinical diagnosis may represent the extreme end of a continuous distribution of inattentive and hyperactive behaviors. This hypothesis can be tested by assessing the predictive value of polygenic risk scores derived from a discovery sample of ADHD patients in a target sample from the general population with continuous scores of inattention and hyperactivity. In addition, the genetic overlap between ADHD and continuous ADHD scores can be tested across rater and age.
The Psychiatric Genomics Consortium has performed the largest genome-wide analysis (GWA) study of ADHD so far, including 5,621 clinical patients and 13,589 controls. The effects sizes of single nucleotide polymorphisms (SNPs) estimated in this meta-analysis were used to obtain individual polygenic risk scores in an independent population-based cohort of 2,437 children from the Netherlands Twin Register. The variance explained in Attention Problems (AP) scale scores by the polygenic risk scores was estimated by linear mixed modeling.
The ADHD polygenic risk scores significantly predicted both parent and teacher ratings of AP in preschool- and school-aged children.
These results indicate genetic overlap between a diagnosis of ADHD and AP scale scores across raters and age groups and provides evidence for a dimensional model of ADHD. Future GWA studies on ADHD can likely benefit from the inclusion of population-based cohorts and the analysis of continuous scores.
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