King's College London

About: King's College London is a education organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Mental health. The organization has 43107 authors who have published 113125 publications receiving 4498103 citations. The organization is also known as: King's & KCL.

Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis

Abstract: RA is a progressive inflammatory autoimmune disease with articular and systemic effects. Its exact cause is unknown, but genetic and environmental factors are contributory. T cells, B cells and the orchestrated interaction of pro-inflammatory cytokines play key roles in the pathophysiology of RA. Differentiation of naive T cells into Th 17 (T(H)17) cells results in the production of IL-17, a potent cytokine that promotes synovitis. B cells further the pathogenic process through antigen presentation and autoantibody and cytokine production. Joint damage begins at the synovial membrane, where the influx and/or local activation of mononuclear cells and the formation of new blood vessels cause synovitis. Pannus, the osteoclast-rich portion of the synovial membrane, destroys bone, whereas enzymes secreted by synoviocytes and chondrocytes degrade cartilage. Antigen-activated CD4(+) T cells amplify the immune response by stimulating other mononuclear cells, synovial fibroblasts, chondrocytes and osteoclasts. The release of cytokines, especially TNF-α, IL-6 and IL-1, causes synovial inflammation. In addition to their articular effects, pro-inflammatory cytokines promote the development of systemic effects, including production of acute-phase proteins (such as CRP), anaemia of chronic disease, cardiovascular disease and osteoporosis and affect the hypothalamic-pituitary-adrenal axis, resulting in fatigue and depression.

Analytic approaches to twin data using structural equation models

Abstract: The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.

MicroRNA related polymorphisms and breast cancer risk

Abstract: Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Flavonoids in health and disease

Abstract: Occurrence and analysis: analysis and identification of flavonoids in practice phenolic acids in fruits flavonoids in medical plants. Chemical and biochemical properties: chemistry of flavonoids antioxidant properties of flavonoids, reduction potentials, and electron transfer reactions of flavonoid radicals flavonoid and metal interactions in biological systems inhibition of mitochondrial function by flavonoids. Antioxidant activities: structure-antioxidant activity relationships of flavonoids and isoflavonoids structural aspects of antioxidant activity of flavonoids effects of flavonoids on the oxidation of low density lipoprotein flavonoids as inhibitors of lipid peroxidation in membranes isoflavonoids as inhibitors of lipid peroxidation and quenchers of singlet oxygen. Nutritional studies: ginkgo biloba extract EG6 761 - biological actions, antioxidant activity, and regulation of nitric oxide synthase nutritional studies of flavonoids in wine nutrition of grape phenolics flavonoids and phenylpropanoids as contributors to the antioxidant activity of fruit juices pycnogenol. In Vivo effects: anti-cancer properties of flavonoids, with emphasis on citrus flavonoids quercetin in foods, cardiovascular disease, and cancer absorption, metabolism, and bioavailability of flavonoids flavonoids and coronary heart disease-dietary perspectives.