FTO gene polymorphisms and obesity risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (<it>FTO</it>); however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion.</p> <p>Methods</p> <p>We searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR) and their 95% confidence intervals (CI) were estimated using per-allele comparison. Summary ORs were estimated using a random effects model.</p> <p>Results</p> <p>We identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36), rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53), rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38), rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68), and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62). Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with <it>I</it>²test values ranging from 38.1% to 84.5%.</p> <p>Conclusions</p> <p>This meta-analysis suggests that <it>FTO </it>may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.</p

Heterologous Expression and Patch-Clamp Recording of P2X Receptors in HEK293 Cells

P2X receptors (P2XRs) are ligand-gated ion channels gated by extracellular adenosine 5′-triphosphate (ATP) and play a critical role in mediating ATP-induced purinergic signaling in physiological and pathological processes. Heterologous expression of P2XR in human embryonic kidney 293 (HEK293) cells and measurement of P2XR-mediated currents using patch-clamp recording technique have been widely used to study the biophysical and pharmacological properties of these receptors. Combination of electrophysiology with site-directed mutagenesis and structural information has shed light on the molecular basis for receptor activation and mechanisms of actions by receptor antagonists and modulators. It is anticipated that such methodologies will continue helping us to provide more mechanistic understanding of P2XRs and to test novel receptor antagonists and allosteric modulators for therapeutical purposes. In this chapter, we describe protocols of transiently or stably expressing the P2XR in HEK293 cells and measuring P2XR-mediated currents by using whole-cell recording

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Cross-sectional study of correlation between mandibular incisor crowding and third molars in young Brazilians

Objectives: The aim of this study was to evaluate transversally the clinical correlation between lower incisor crowding and mandible third molar. Study Design: Three hundred healthy volunteers (134 male and 166 female), aged 20.4 (+/- 2.4) years-old were submitted to a complete clinical examination and filled up a questionnaire about gender, age, total teeth number and presence or absence of superior and inferior third molar. After a recent panoramic radiography were evaluated. The multiple logistic regression showed that none of the studied factors influenced the mandibular incisor crowding. Results: The proportion of both molars present or both absent was higher than the other conditions (Chi-square, p.05) the mandibular incisor crowding. Despite the statistical significance, wear orthodontics appliances showed a little correlation (odds ratios < 1.0) in the mandibular incisor crowding. Conclusion: Presence of maxillary and/or mandibular third molars has no relation with the lower incisor crowding.183E505E50