To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. ...For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter approximately 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4 x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.
Background During fractional flow reserve (FFR) measurements, distal coronary pressure (Pd) can be influenced by hydrostatic pressure changes resulting from the height difference (HD) between the ...coronary ostium and the location of the distal pressure sensor. Aims We investigated the effect of aortocoronary HD on the FFR measurements in each coronary artery. Methods In this retrospective cohort study, we analyzed 257 patients who underwent FFR measurements and coronary computed tomography (CCTA) within a year. Using CCTA, we measured HD as the vertical distance between the coronary ostium and a matched point of the distal coronary pressure sensor identified on coronary angiography. Results The location of the Pd sensor was higher than the coronary ostium in the left anterior descending artery (LAD) (-4.64 ± 1.15 cm) and lower than the coronary ostium in the left circumflex artery (LCX) (2.54 ± 1.05 cm) and right coronary artery (RCA) (2.03 ± 1.28 cm). The corrected FFR values by HD were higher in the LAD (0.78 ± 0.09 to 0.82 ± 0.09, P<0.01) and lower in the LCX and RCA than the original FFR values (0.87 ± 0.07 to 0.85 ± 0.08, P<0.01; 0.87 ± 0.10 to 0.86 ± 0.10, P<0.01, respectively). Using an FFR cut-off value of 0.8, the concordance rates between the FFR and corrected FFR values were 77.8%, 95.2%, and 100% in the LAD, LCX, and RCA, respectively. Conclusion HD between the coronary ostium and the distal coronary pressure sensor may affect FFR measurements and FFR-guided treatment decisions for coronary artery disease.
Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle ...structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/β-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression-including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1β, and IL-15-and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/β-catenin signaling pathway, such as in the Wnt families, β-catenin, phosphorylated GSK-3β and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/β-catenin and JAK/STAT pathways in hORSCs.
Abstract Important changes in body composition with aging are a progressive loss of muscle mass and increase of fat mass. Despite their enormous clinical importance, body composition changes such as ...sarcopenic obesity in the elderly are under-recognized. This study aimed to examine the relationship of body composition with a wide variety of cardiometabolic risk factors among 2943 subjects (1250 men and 1693 women) aged 60 years or older from Korean National Health Examination and Nutrition Survey (KNHANES). Sarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by weight (%) of <1 SD below the sex-specific mean for young adults. Obesity was defined as a body mass index (BMI) ≥25 kg/m2 . Body composition was categorized into four non-overlapping groups: the sarcopenic obese, sarcopenic nonobese, nonsarcopenic obese, and nonsarcopenic nonobese groups. A wide variety of cardiometabolic risk factors, including blood pressure (BP), glucose tolerance indices, lipid profiles, inflammatory markers, and vitamin D level, were compared according to body composition group. The prevalence of sarcopenic obesity was 18.4% in men and 25.8% in women. In both sexes, the prevalence of vitamin D deficiency and metabolic syndrome was highly prevalent in the sarcopenic obese group. Serum insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride levels, and ferritin levels were the highest in the sarcopenic obese group in both men and women, whereas HDL-cholesterol and 25-hydroxyvitamin D (25(OH)D) levels were the lowest in the sarcopenic obese group. The sarcopenic obese group was more closely associated with insulin resistance, metabolic syndrome, and cardiovascular disease (CVD) risk factors than any other group in this elderly population.
We propose a wing-shaped composite structure that uses an electroless nickel-plated carbon fabric as an electro-thermal heating element, thus improving the electrical and thermal properties. The ...results showed that the electro-thermal conversion efficiency increased from 0.064 to 0.054 W/°C with increasing plating thickness and weight percentage of the nickel particles deposited. The experiments demonstrated that the surface temperature of the wing-shaped composite could be heated up to 87.9 °C within 1000 s at an applied power density of 2.11 kW/m2. The measurement results agreed well with those of the coupled electro-thermal simulations of heating elements related to a resistance heating phenomenon via an electro-thermal conversion, and it validated the heating performance. In addition, the nickel-plated carbon fabric as a heating element for the leading edge of the wing-shaped model was examined using a multiphysics de-icing simulation under actual icing conditions from a practical perspective. Most of the icing was removed by applying a power density of 2.7 kW/m2 for 600 s to the wing-shaped composite structure. An interlaminar shear strength (ILSS) test was performed to verify the mechanical performance in terms of structural integrity. This practical approach could efficiently offer a desirable solution for the multifunctional de-icing composite field.
Chronic alcohol exposure can lead to alcoholic liver disease,including hepatitis,cirrhosis and hepatocellular carcinoma,and chronic inflammation can simultaneously cause systemic medical ...illness.Recent evidence suggests that alcoholic liver disease is a predictor for liver-related diseases,cardiovascular disease,immunologic disease,and bone disease.Chronic inflammation in alcoholic liver disease is mediated by a direct inflammatory cascade from the alcohol detoxification process and an indirect inflammatory cascade in response to gut microflora-derived lipopolysaccharides(LPS).The pathophysiology of alcoholic liver disease and its related systemic illness is characterized by oxidative stress,activation of the immune cascade,and gut-liver interactions.Integrative therapeutic strategies for alcoholic liver disease include abstaining from alcohol consumption;general anti-inflammatories such as glucocorticoid,pentoxifylline,and tumour necrosis factor-αantagonist;antioxidants such as N-acetylcysteine;gut microflora and LPS modulators such as rifaximin and/or probiotics.This review focuses on the impact of chronic liver inflammation on systemic health problems and several potential therapeutic targets.
Alcoholic liver disease (ALD) is implicated in gut disturbances, both functionally and structurally. It has been noticed that the gut–liver interaction is an important feature in the prevention of ...systemic inflammation as well as liver health. The optimal functioning of the gut–liver axis depends on gut health. Therefore, gut problems may be important for estimating liver inflammation, while our knowledge of ALD could also provide an insight into gut health. Gut problems accompanied by ALD include gut motility and absorption problems, mucosal damage and the dysbiosis of gut microbiota and gastrointestinal carcinogenesis. Moreover, there is emerging evidence that besides direct inflammatory injury caused by alcohol, gut problems related to ALD play a crucial role in the pathogenesis of cardiovascular and immunological disorders. In this regard, we should consider ALD in relation to both gut health and chronic systemic low‐grade inflammation. Accordingly, integrative therapeutic strategies are warranted for treating and preventing ALD and systemic inflammation as well as alcohol‐related gut problems.
Polo-like kinase 1 (PLK1) is a critical regulator of cell cycle progression and apoptosis. However, its regulation remains poorly understood. In the present study, we investigated the molecular ...mechanism underlying the post-transcriptional regulation of PLK1. We observed that heterogeneous nuclear ribonucleoprotein K (hnRNPK) and PLK1 were positively associated in several different cancers and high expression levels of them correlated with poor prognosis in patients with cancer. Knockdown of hnRNPK resulted in reduced expression of PLK1, whereas conversely, PLK1 expression was increased in hnRNPK-overexpressing cells. We found that hnRNPK regulated PLK1 expression through KH1- and KH2-dependent interactions with the 3'UTR of PLK1 mRNA. In addition, microRNA-149-3p (miR-149-3p) and miR-193b-5p suppressed PLK1 expression by targeting the 3'UTR of PLK1 mRNA. MicroRNA-elicited enrichment of PLK1 mRNA in Ago2 immunoprecipitation was altered by the presence or absence of hnRNPK. Furthermore, the deletion of the cytosine (C)-rich sequences of the 3'UTR of PLK1 mRNA abolished the decreased PLK1 expression observed via hnRNPK silencing and administration of miRNAs, a finding that suggests that hnRNPK shares this C-rich motif with miR-149-3p and miR-193b-5p. We also found that downregulation of PLK1 by either silencing hnRNPK or overexpression of miR-149-3p and miR-193b-5p decreased clonogenicity and induced apoptosis. Our findings from this study demonstrate that hnRNPK regulates PLK1 expression by competing with the PLK1-targeting miRNAs, miR-149-3p and miR-193b-5p.
Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its ...causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro‐inflammatory cytokines and antimicrobial peptides by three different Malassezia species—M. restricta, M. globosa and M. sympodialis—in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide‐binding oligomerisation domain, leucine‐rich repeat and pyrin‐domain‐containing protein (NLRP)3–apoptosis‐associated speck‐like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)‐1β secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, β‐defensin 2, and LL‐37. IL‐8 mRNA and IL‐22 protein significantly increased in the M. sympodialis‐treated group, and Chemokine C–C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa‐ and M. restricta‐ treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro‐inflammatory cytokines and chemokines, and antimicrobial peptides.
Purpose
The oxidative balance score (OBS) comprises dietary and non-dietary lifestyle pro-oxidants and antioxidants. Elevated serum γ-glutamyltransferase (GGT) level has currently emerged as a ...biomarker of oxidative stress. In this study, we examined whether OBS was inversely associated with serum GGT level and whether OBS could be a useful marker to predict GGT among Korean adults.
Methods
This cross-sectional study was based on data obtained from the 2010 and 2011 Korea National Health and Nutrition Examination Survey. 2087 men and 2071 women were included in final analysis. The OBS was divided into five equal interval categories, and GGT was dichotomized into low and high using its sex-specific median value. Multiple logistic regression analysis was conducted to assess the association between OBS categories and high GGT.
Results
Compared with the lowest OBS category as reference, the multivariable adjusted ORs (95% CIs) for the highest OBS category of men and women were 0.05 (0.01–0.19) and 0.27 (0.09–0.78), respectively (
p
for trend <0.01).
Conclusion
A higher OBS that indicates a predominance of antioxidant over pro-oxidant exposure was strongly inversely associated with GGT level among Korean adults.
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