Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 70
Filtrar
1.
Clin Cosmet Investig Dermatol ; 17: 891-900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660588

RESUMO

Purpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients' quality of life(QoL). Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test. Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis. Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient's QoL.

2.
Geroscience ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438772

RESUMO

Machine learning models are increasingly being used to estimate "brain age" from neuroimaging data. The gap between chronological age and the estimated brain age gap (BAG) is potentially a measure of accelerated and resilient brain aging. Brain age calculated in this fashion has been shown to be associated with mortality, measures of physical function, health, and disease. Here, we estimate the BAG using a voxel-based elastic net regression approach, and then, we investigate its associations with mortality, cognitive status, and measures of health and disease in participants from Atherosclerosis Risk in Communities (ARIC) study who had a brain MRI at visit 5 of the study. Finally, we used the SOMAscan assay containing 4877 proteins to examine the proteomic associations with the MRI-defined BAG. Among N = 1849 participants (age, 76.4 (SD 5.6)), we found that increased values of BAG were strongly associated with increased mortality and increased severity of the cognitive status. Strong associations with mortality persisted when the analyses were performed in cognitively normal participants. In addition, it was strongly associated with BMI, diabetes, measures of physical function, hypertension, prevalent heart disease, and stroke. Finally, we found 33 proteins associated with BAG after a correction for multiple comparisons. The top proteins with positive associations to brain age were growth/differentiation factor 15 (GDF-15), Sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SEVP 1), matrilysin (MMP7), ADAMTS-like protein 2 (ADAMTS), and heat shock 70 kDa protein 1B (HSPA1B) while EGF-receptor (EGFR), mast/stem-cell-growth-factor-receptor (KIT), coagulation-factor-VII, and cGMP-dependent-protein-kinase-1 (PRKG1) were negatively associated to brain age. Several of these proteins were previously associated with dementia in ARIC. These results suggest that circulating proteins implicated in biological aging, cellular senescence, angiogenesis, and coagulation are associated with a neuroimaging measure of brain aging.

3.
Org Lett ; 25(43): 7800-7804, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37874767

RESUMO

Chemo and regioselective dialkylation of alkene is an efficient protocol for constructing useful chemicals, but challenges remain in the unrestricted application of alkylating reagents. Alkyl bromide belongs to the easy-to-access and operable alkyl electrophiles that can be used in reductive coupling with alkenes. Here, we reported convenient strategies for dialkylcyclization and homodialkylation of unactivated ß,γ- and γ,δ-unsaturated alkenyl amides with 1,3-dibromoalkanes or primary alkyl bromides under nickel-catalyzed reductive conditions that exhibited high regioselectivity and functional-group tolerance.

4.
Chem Commun (Camb) ; 59(69): 10420-10423, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37554108

RESUMO

Photoredox alkene or alkyne alkylsulfonylation has been achieved with phthalimide esters and sulfinates providing unexpected α-sulfones. Mechanistic studies disclose that the preferential alkyl radical addition to the alkene or the Markovnikov hydrosulfonation of the alkyne should contribute to the formation of the ß-alkylated α-sulfones. Moreover, the reaction is easy to operate covering quite large substrate scales including primary, secondary and tertiary alkyl groups and all sorts of terminal aryl alkenes or alkynes. Besides, the reaction was also suitable for the sulfonylation of several drug molecules.

5.
Int Arch Occup Environ Health ; 96(8): 1123-1136, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37400582

RESUMO

OBJECTIVE: The current study aims to explore the effects of nine urine monohydroxy PAH metabolites (OHPAH) including 1-hydroxynaphthalene (1-OHNAP), 2-hydroxynaphthalene (2-OHNAP), 3-hydroxyfluorene (3-OHFLU), 9-hydroxyfluorene (9-OHFLU), 1-hydroxyphenanthrene (1-OHPHE), 2-hydroxyphenanthrene (2-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), and 1-hydroxypyrene (1-OHPYR) on current asthma in people in the United States using a variety of statistical techniques. METHODS: A cross-sectional examination of a subsample of 3804 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) was conducted between 2007 and 2012. To investigate the relationship between urine OHPAHs levels and current asthma, multivariate logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were utilized. RESULTS: In the multivariate logistic regression model, after controlling for confounders, urine 2-OHPHE was associated with current asthma in both male (AOR = 7.17, 95% CI: 1.28-40.08) and female (AOR = 2.91, 95% CI: 1.06-8.01) smokers. In the qgcomp analysis, 2-OHPHE (39.5%), 1-OHNAP (33.1%), and 2-OHNAP (22.5%) were the major positive contributors to the risk of current asthma (OR = 2.29, 95% CI: 0.99, 5.25), and in female smokers, 9-OHFLU (25.8%), 2-OHFLU (21.5%), and 2-OHPHE (15.1%) were the major positive contributors (OR = 2.19, 95% CI: 1.06, 4.47). The results of the BKMR model basically agreed with qgcomp analysis. CONCLUSION: Our results demonstrate a strong association of urine 2-OHPHE with current asthma, and further longitudinal studies are needed to understand the precise relationship between PAH exposure and current asthma risk.


Assuntos
Asma , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Teorema de Bayes , Hidrocarbonetos Policíclicos Aromáticos/urina , Asma/epidemiologia , Biomarcadores/análise
6.
Indian J Dermatol ; 68(2): 235, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275825
7.
Environ Res ; 217: 114907, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36436553

RESUMO

The global burden of hypertension, the major cause of cardiovascular disease (CVD) globally, remains unresolved. Exposure to PM2.5 has been linked to hypertension (HTN) in adults and the elderly globally according to previous studies. Nonetheless, evidence on the association of polycyclic aromatic hydrocarbon (PAH) exposure and HTN risk in the general adult population in the United States was limited. To investigate the relationship between PAH exposure and HTN in adults in the United States, cross-sectional data during 2003 and 2016 from the National Health and Nutrition Examination Survey (NHANES) on a stratified multistage random sample of the civilian non-institutionalized population were utilized. After eliminating individuals with incomplete information of interest, the final analysis contained 8951 subjects aged ≥20. In the multivariate logistic regression model, 1-hydroxynaphthalene and 2-hydroxyfluorene were found positively associated with increased risk of HTN among overall participants after adjusting for the covariates. 1-hydroxynaphthalene and 2-hydroxynaphthalene showed positive associations with HTN risk among overweight participants. In the Bayesian kernel machine regression (BKMR) model, 1-hydroxynaphthalene and 2-hydroxyfluorene presented great importance to HTN risk among overall individuals. In the male subgroup analyses by BKMR, 2-hydroxyfluorene presented a positive effect on HTN risk when the remaining OH-PAHs were set at their 25th, 50th, and 75th percentile. Our findings highlight the complexities of estimating the risk of HTN associated with mixed PAH exposure, and additional longitudinal studies are required to determine the exact link between PAH exposure and HTN risk, as well as the underlying mechanisms.


Assuntos
Hipertensão , Hidrocarbonetos Policíclicos Aromáticos , Idoso , Adulto , Humanos , Masculino , Estados Unidos/epidemiologia , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Inquéritos Nutricionais , Estudos Transversais , Teorema de Bayes , Biomarcadores , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia
8.
Environ Sci Pollut Res Int ; 29(56): 84034-84048, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36241831

RESUMO

During the last 20 years, the association between polycyclic aromatic hydrocarbons (PAHs) and health risk has become one of the hotspots in the fields of public health and the environment. A bibliometric study of 1392 research articles retrieved from the Web of Science Core Collection (WoSCC) published between 2002 and 2021 was performed to give an in-depth statistical evaluation of research progress and future trends on PAHs and health risk (PHR). According to the findings, the annual output of significant scientific papers increased exponentially. China ranked first among the 86 nations in terms of the number of publications (NP), followed by the USA and India. Logistic regression analysis showed that there was a positive relationship between the second tertile of 180-day usage count (AOR = 1.62; 95% CI: 1.16-2.26) and increased odds of open access publishing after adjustment for the confounders, indicating that open access papers on PHR were more preferred over the preceding 6 months than non-open access articles. The most popular terms were "PAHs," "risk assessment," and "source identification." According to the bibliometric study, the research hotspots that require more exploration include identifying PAH sources in media such as soil, water, dust, and food and evaluating their linkages to health hazards using appropriate risk models. Understanding the environmental behavior, bioavailability, and health concerns of PAHs and their derivatives in various media is critical for environmental and public health protection. This paper provides an overview of current research status and future perspectives for PHR research.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental , Poeira/análise , Solo , Bibliometria , China
9.
Telemed Rep ; 3(1): 166-173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204703

RESUMO

Background: Telemedicine has experienced rapid growth in China, with wide applications for chronic disease management. Objective: This study examined a unique survey dataset to identify the provision of telemedicine services by dermatologists, and to explore its association with physician characteristics, perception of diagnosis, and physicians' perceptions of the advantages and disadvantages of telemedicine. Materials and Methods: Responses to an anonymous voluntary questionnaire were collected from 238 dermatologists in Zhejiang Province, China, via a mixed mode of online and in-person data collection. Data were analyzed using Stata 16.0. Empirical analyses utilized descriptive statistics and multivariable logistical regression. Results: Among a total of 238 physicians, 34.9% provided telemedicine services. Results from the multivariable logistic regression indicated that, if physicians can use their spare time to help patients, seniority and their perception of the benefit of telemedicine are the two most important factors determining their likelihood of providing telemedicine services among the studied sample. Conclusion: Telemedicine holds great promise, but its practices need to be more efficient to save time and reduce the risk of misdiagnosis so that more physicians may participate.

12.
Circ Genom Precis Med ; 14(4): e003258, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34241534

RESUMO

BACKGROUND: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis. METHODS: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. RESULTS: We replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P<3.1×10-4) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near CDKN2B-AS1 and rs11170820 near FLJ12825 for CAC, and rs7412 near APOE for cIMT). CONCLUSIONS: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.


Assuntos
Aterosclerose/genética , População Negra/genética , Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Loci Gênicos , Predisposição Genética para Doença , População Branca/genética , Estudo de Associação Genômica Ampla , Humanos
13.
PLoS One ; 16(5): e0251423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014961

RESUMO

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (ß = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (ß = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; ß = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; ß = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; ß = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.


Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 2/sangue , Vitamina D/análogos & derivados , Negro ou Afro-Americano/genética , Idoso , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Vitamina D/sangue , Vitamina D/genética , Proteína de Ligação a Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética
14.
BMC Public Health ; 21(1): 754, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33874932

RESUMO

BACKGROUND: To determine if individuals with food insecurity (FI) were less likely to have seen a mental health professional (MHP) within the past year than individuals without FI. METHODS: This is a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 2007 and 2014. All participants 20 years of age or older were eligible for this study. We excluded participants who were pregnant, missing FI data, or missing data from the Patient Health Questionnaire (PHQ-9). The primary outcome was self-reported contact with a MHP in the past 12 months. We used multivariable logistic regression models to test the association between FI and contact with a MHP, controlling for all demographic and clinical covariates. RESULTS: Of the 19,789 participants, 13.9% were food insecure and 8.1% had major depressive disorder (MDD). In bivariate analysis, participants with FI were significantly more likely to have MDD (5.3% vs 2.8%, p < 0.0001) and to have been seen by a MHP in the preceding 12 months (14.0% vs 6.9%, p < 0.0001). In multivariable models, adults with FI had higher odds of having seen a MHP (OR = 1.32, CI: 1.07, 1.64). CONCLUSIONS: This study demonstrates that individuals with FI were significantly more likely to have seen a MHP in the preceding 12 months compared to individuals without FI. Given the growing interest in addressing unmet social needs in healthcare settings, this data suggests that visits with MHPs may be a valuable opportunity to screen for and intervene on FI.


Assuntos
Transtorno Depressivo Maior , Insegurança Alimentar , Adulto , Estudos Transversais , Feminino , Abastecimento de Alimentos , Humanos , Saúde Mental , Inquéritos Nutricionais , Gravidez , Estados Unidos/epidemiologia
15.
Eur J Dermatol ; 31(1): 32-40, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648912

RESUMO

BACKGROUND: Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken sebaceous glands (SGs) containing de-differentiated cells, however the role of P. acnes is unclear. OBJECTIVES: To investigate the effects of P. acnes on aryl hydrocarbon receptor (AhR) activation, lipogenesis and differentiation in cultured immortalized human SZ95 sebocytes. MATERIALS & METHODS: Cultured sebocytes were incubated with formalin-killed (f-) P. acnes (f-P. acnes) at different ratios of multiplicity of infection. The mRNA levels of the AhR downstream cytochrome P450 (CYP) genes were measured by quantitative RT-PCR, nuclear translocation of AhR by western blot and immunofluorescence, lipogenesis and keratinization by gene set enrichment analysis (GSEA), lipid related analysis by Oil red O staining and Nile red staining, and sebaceous differentiation-related gene expression by western blot. RESULTS: f-P. acnes upregulated CYPs mRNA levels and induced translocation of AhR protein from the cytoplasm into the nucleus. GSEA revealed downregulation of lipogenesis and upregulation of keratinization. f-P. acnes inhibited linoleic acid-induced neutral lipid synthesis and expression of sebocyte markers, keratin 7 and mucin1/EMA, but increased expression of keratinocyte markers, keratin 10 and involucrin, which were abolished by AhR gene silencing. Inhibition of lipogenesis-related genes, such as sterol response element-binding protein, was also observed. CONCLUSION: f-P. acnes inhibits lipogenesis and induces terminal differentiation of sebocytes, into keratinocyte-like cells, via activation of the AhR pathway in vitro, suggesting that follicular P. acnes is not only acnegenic but also promotes acne remission through feedback regulation of sebum production.


Assuntos
Diferenciação Celular/fisiologia , Formaldeído/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Propionibacterium acnes/fisiologia , Receptores de Hidrocarboneto Arílico/fisiologia , Glândulas Sebáceas/citologia , Células Cultivadas , Humanos
16.
RSC Adv ; 11(59): 37083-37088, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-35496447

RESUMO

A new one pot protocol has been developed for the reductive silylation of alkenyl methyl ethers using Et3Si-BPin and HSiEt3 with nickel(ii) catalyst. Styrene type methyl ethers, multi-substituted vinyl methyl ethers, heterocycles and unconjugated vinyl ethers are all tolerated to form alkyl silanes. Mechanistic study reveals that it is a cascade of a C-O bond silylation and vinyl double bond hydrogenation process. Internal nucleophilic substitution or oxidative addition pathways were both acceptable for C-O bond cleavage. The acquired intermediate alkenyl silanes then proceeded through an unconventional reduction process thus providing alkyl silanes.

17.
J Hypertens ; 38(8): 1567-1577, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32371767

RESUMO

BACKGROUND: Patients with stage 1 systolic hypertension have increased risk of cardiovascular disease (CVD) events. METHODS: Using Cox models, we assess the effect of targeting an intensive SBP goal of less than 120 mmHg compared with standard SBP goal of less than 140 mmHg on the risk of CVD events in adults with stage 1 systolic hypertension with diabetes mellitus enrolled in Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) (n = 1901) and without diabetes mellitus enrolled in Systolic Blood Pressure Intervention Trial (SPRINT) (n = 3484) that used identical SBP goal interventions. OUTCOMES: In ACCORD BP, the primary composite CVD outcome was the first occurrence of myocardial infarction, stroke, or CVD mortality. In SPRINT, the primary composite CVD outcome was the first occurrence of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or CVD mortality. RESULTS: In SPRINT, targeting an intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.75 (95% confidence interval, 0.58-0.98); events 1.78 vs. 2.37%/year]. In ACCORD BP, the relationships of SBP goal with the primary CVD outcome was modified by the glycemia goal intervention (interaction P = 0.039). In the standard glycemia subgroup (A1c target 7-7.9%), intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.61 (0.40-0.94); events 1.63 vs. 2.56%/year]. In the intensive glycemia subgroup (A1c target <6%), the risk of the primary CVD outcome was not significantly different between groups [hazard ratio 1.20 (0.76-1.89); events 1.91 vs. 1.60%/year]. CONCLUSION: Targeting an intensive SBP goal significantly reduced the risk of CVD events in patients with stage 1 systolic hypertension without diabetes and with diabetes on standard glycemia goal.


Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares , Complicações do Diabetes , Adulto , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Humanos , Fatores de Risco , Sístole/fisiologia
18.
Dermatology ; 236(4): 345-360, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31694017

RESUMO

OBJECTIVES: The effect of breastfeeding on atopic dermatitis (AD) remains controversial. To determine the association -between breastfeeding and AD, we conducted an updated meta-analysis of prospective cohort studies. METHODS: A comprehensive search of PubMed, EMBASE, MEDLINE and Cochrane Library was conducted. Studies meeting the predetermined criteria were evaluated by 2 authors independently. The pooled relative risk (RR) adjusted for confounders with its 95% CI was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis and meta-regression. RESULTS: A total of 27 studies were included for meta-analysis. The pooled estimates for the effect of total and exclusive breastfeeding on AD were 1.01 (95% CI 0.93-1.10) and 0.99 (95% CI 0.88-1.11), respectively. Heterogeneity was substantial across studies (total: p < 0.01 or I2 = 65.2%; exclusive: p < 0.01 or I2 = 72.3%). There was a weak evidence for a protective effect of breastfeeding against AD in cohorts with atopic heredity (total: RR 0.85, 95% CI 0.74-0.98; exclusive: RR 0.83, 95% CI 0.70-0.97). In cohorts without atopic heredity, the effect shifted to the risk side when limited to exclusive breastfeeding (RR 1.19, 95% CI 1.02-1.40) while it dropped towards null when limited to total breastfeeding (RR 1.11, 95% CI 0.94-1.31). CONCLUSIONS: There is no association between AD and breastfeeding, regardless of total or exclusive breastfeeding patterns. There is some evidence for a protective function of exclusive and total breastfeeding in a cohort with atopic heredity. The effect shifts to the risk side in cohorts without atopic heredity. However, these findings should be interpreted with caution because heterogeneity is evident.


Assuntos
Aleitamento Materno , Dermatite Atópica/epidemiologia , Dermatite Atópica/prevenção & controle , Adulto , Aleitamento Materno/estatística & dados numéricos , Criança , Estudos de Coortes , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco
19.
Nat Genet ; 51(11): 1580-1587, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31659325

RESUMO

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.


Assuntos
Aterosclerose/patologia , Predisposição Genética para Doença , Histona Desacetilases/metabolismo , Histona Desacetilases/fisiologia , Contração Muscular , Músculo Liso Vascular/patologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/fisiologia , Calcificação Vascular/patologia , Idoso , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Estudos de Coortes , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Estudo de Associação Genômica Ampla , Histona Desacetilases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Calcificação Vascular/genética , Calcificação Vascular/metabolismo
20.
J Innate Immun ; 11(1): 41-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30056444

RESUMO

Activation of Toll-like receptor (TLR)-2 and subsequent inflammatory response contribute to lesion development in acne vulgaris. A cross-talk between aryl hydrocarbon receptor (AhR), a cytosolic receptor protein that responds to environmental and physiological stress, and TLRs has recently been reported. In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF-α and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhanced TNF-α and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-κB was strengthened by TCDD and repressed by CH223191. AhR inhibition by transfecting shRNA blocked the ability of PGN to stimulate phosphorylation of p38MAPK and p65NF-κB in SZ95 sebocytes. Overall, these data demonstrate that AhR is able to modulate PGN-induced expression of TNF-α and IL-8 in human SZ95 sebocytes involving the MyD88-p65NF-κB/p38MAPK signaling pathway, which probably indicates a new mechanism in TLR2-mediated acne.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Interleucina-8/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Acne Vulgar/fisiopatologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Células Cultivadas , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Humanos , Inflamação , Fator 88 de Diferenciação Mieloide/metabolismo , Peptidoglicano/imunologia , Peptidoglicano/metabolismo , Dibenzodioxinas Policloradas/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/imunologia , Glândulas Sebáceas/imunologia , Glândulas Sebáceas/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA