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1.
Artigo em Inglês | MEDLINE | ID: mdl-33492019

RESUMO

OBJECTIVES: To systematically analyze available prospective evidence on the association between HIV infection and incident heart failure (HF). METHODS: A systematic search of PubMed, EMBASE, Web of Science, and manual search of relevant articles through June 1st, 2020, was conducted. Two authors independently performed full-text assessments and data extraction. Pooled relative risk (RR) with 95% confidence interval (CI) were estimated using DerSimonian and Laird random-effects models, with inverse-variance fixed-effects meta-analysis used as a sensitivity analysis. Heterogeneity was explored using subgroup analyses and meta-regressions. RESULTS: We included 8 reports among 8,848,569 participants with 101,335 incident cases of HF (1,941 among 131,632 people living with HIV (PLWH) and 99,394 among 8,716,937 control participants). In the overall analysis using a random-effect model, HIV infection was positively associated with incident HF (RR, 1.80 [95%CI, 1.51-2.15]), though with significant heterogeneity. A similar association was observed with a fixed-effects model, 1.59 (1.50-1.68). In subgroup analyses, associations between HIV infection and HF were nominally stronger in younger adults (age<50 years), women, and individuals with low CD4 count (<200 cells/mm3). Publication bias was suggested from visual examination of funnel plots, correcting for this did not abolish the association, 1.52 (1.25-1.85). CONCLUSIONS: Our meta-analysis provides additional evidence that HIV is associated with an increased risk of HF, particularly among younger adults, women, and individuals with low CD4 count.

2.
Crit Care Med ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196528

RESUMO

OBJECTIVES: Existing studies evaluating the accuracy of heparin-binding protein for the diagnosis of sepsis have been inconsistent. We conducted a systematic review and meta-analysis to assess the totality of current evidence regarding the utility of heparin-binding protein to diagnose sepsis in patients with presumed systemic infection. DATA SOURCE: PubMed, Embase, the China National Knowledge infrastructure, and WangFang electronic database were searched from inception to December of 2019. STUDY SELECTION: Two independent reviewers identified eligible studies. Cohort and case-control studies, which measured serum levels of heparin-binding protein among adult patients with suspected sepsis, were eligible for inclusion. DATA EXTRACTION: Two reviewers independently extracted data elements from the selected studies. A bivariate random-effects meta-analysis model was used to synthesize the prognostic accuracy measures. Risk of bias of studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tool. DATA SYNTHESIS: We identified 26 studies with 3,868 patients in the meta-analysis. Heparin-binding protein had a pooled sensitivity of 0.85 (95% CI, 0.79-0.90) and a pooled specificity of 0.91 (95% CI, 0.82-0.96) for the diagnosis of sepsis. There was low heterogeneity between the studies (I = 12%), and no evidence of publication bias was detected. Heparin-binding protein had a higher sensitivity and specificity when compared with procalcitonin (0.75 [95% CI, 0.62-0.85] and 0.85 [95% CI, 0.73-0.92]) as well as C-reactive protein (0.75 [95% CI, 0.65-0.84] and 0.71 [95% CI, 0.63-0.77]). Serial measurements of heparin-binding protein also showed that heparin-binding protein levels rose significantly at least 24 hours before a diagnosis of sepsis. CONCLUSIONS: The diagnostic ability of heparin-binding protein is favorable, demonstrating both high sensitivity and specificity in predicting progression to sepsis in critically ill patients. Future studies could assess the incremental value that heparin-binding protein may add to a multimodal sepsis identification and prognostication algorithm for critically ill patients.

5.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2332-2342, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32856611

RESUMO

BACKGROUND: Insulin-like growth factor-1 (IGF-1) has been implicated in several malignancies, but few studies have examined multiple cancers simultaneously. We sought to conduct systematic assessments of the association between IGF-1 and cancer risk. METHODS: We conducted a prospective analysis between IGF-1 and incident total and 19 site-specific cancers among 412,645 individuals enrolled in the UK Biobank with follow-up to 2016. IGF-1 was measured using blood samples provided at the baseline examination. HR and 95% confidence interval (CI) were calculated with multivariable-adjusted Cox models with IGF-1 modeled both in sex-specific quintiles and continuously. RESULTS: Participants were followed for a median of 7.2 years. We observed positive associations between circulating IGF-1 and overall cancer risk for both men (HR = 1.03 per 5-nmol/L increment in IGF-1; 95% CI, 1.01-1.06) and women (HR = 1.03; 95% CI, 1.01-1.06). For specific sites, we observed positive associations for breast (HR = 1.10; 95% CI, 1.07-1.14), prostate (1.09; 95% CI, 1.05-1.12), colorectum (1.07; 95% CI, 1.02-1.11), melanoma (1.08; 95% CI, 1.01-1.15), kidney (1.10; 95% CI, 1.00-1.20), and thyroid (1.22; 95% CI, 1.05-1.42) and inverse associations for lung (0.91; 95% CI, 0.86-0.96), ovaries (0.86; 95% CI, 0.77-0.95), head and neck (0.90; 95% CI, 0.82-0.99), and liver (0.32; 95% CI, 0.26-0.38). The inverse association between IGF-1 and lung cancer was observed only in ever-smokers (HRever-smoker = 0.88 vs. HRnever-smoker = 1.14; Pinteraction = 0.0005). Analyses comparing extreme quintiles were consistent. CONCLUSIONS: IGF-1 is modestly associated with increased risk of total cancer in both men and women but demonstrated divergent associations for site-specific cancers. IMPACT: Our study suggests that IGF-1 could serve as a target for cancer prevention or treatment.

6.
Diabetes Care ; 43(2): 265-271, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959642

RESUMO

Prevailing dietary guidelines have widely recommended diets relatively low in red and processed meats and high in minimally processed plant foods for the prevention of chronic diseases. However, an ad hoc research group called the Nutritional Recommendations (NutriRECS) consortium recently issued "new dietary guidelines" encouraging individuals to continue their current meat consumption habits due to "low certainty" of the evidence, difficulty of altering meat eaters' habits and preferences, and the lack of need to consider environmental impacts of red meat consumption. These recommendations are not justified, in large part because of the flawed methodologies used to review and grade nutritional evidence. The evidence evaluation was largely based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria, which are primarily designed to grade the strength of evidence for clinical interventions especially pharmacotherapy. However, the infeasibility for conducting large, long-term randomized clinical trials on most dietary, lifestyle, and environmental exposures makes the criteria inappropriate in these areas. A separate research group proposed a modified and validated system for rating the meta-evidence on nutritional studies (NutriGRADE) to address several limitations of the GRADE criteria. Applying NutriGRADE, the evidence on the positive association between red and processed meats and type 2 diabetes was rated to be of "high quality," while the evidence on the association between red and processed meats and mortality was rated to be of "moderate quality." Another important limitation is that inadequate attention was paid to what might be replacing red meat, be it plant-based proteins, refined carbohydrates, or other foods. In summary, the red/processed meat recommendations by NutriRECS suffer from important methodological limitations and involve misinterpretations of nutritional evidence. To improve human and planetary health, dietary guidelines should continue to emphasize dietary patterns low in red and processed meats and high in minimally processed plant foods such as fruits and vegetables, whole grains, nuts, and legumes.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Comportamento Alimentar/fisiologia , Carne/efeitos adversos , Carne Vermelha/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Dieta/estatística & dados numéricos , Projetos de Pesquisa Epidemiológica , Manipulação de Alimentos/estatística & dados numéricos , Preferências Alimentares/fisiologia , Frutas/fisiologia , Humanos , Nozes/fisiologia , Estudos Observacionais como Assunto/normas , Estudos Observacionais como Assunto/estatística & dados numéricos , Fatores de Risco , Verduras/fisiologia , Grãos Integrais/fisiologia
7.
J Gerontol A Biol Sci Med Sci ; 75(11): 2200-2206, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31588954

RESUMO

BACKGROUND: There remains a relative paucity of evidence for the association between changes in depressive symptoms with cardiovascular disease (CVD) and mortality. This study aimed to evaluate the association of change in depressive symptoms and incident CVD and mortality in a large prospective cohort of middle-aged and older adults. METHODS: A total of 6,810 participants free of CVD in the China Health and Retirement Longitudinal Study with two assessments of depressive symptoms at wave 1 (2011-2012) and wave 2 (2013-2014) were included. Elevated depressive symptoms were defined as a score of ≥12 on the 10-item Center for Epidemiologic Studies Depression scale. We used a modified Poisson regression to examine the association of changes in depressive symptoms (never, onset, remitted, and persistent) and incident CVD (a composite endpoint of heart disease or stroke) and mortality at wave 3 (2015-2016). RESULTS: During follow-up, 457 CVDs and 148 deaths occurred. Multivariable analyses revealed that persistent depressive symptoms were associated with an elevated risk of CVD (risk ratio = 1.77, 95% confidence interval = 1.38-2.26) and mortality (risk ratio = 1.63, 95% confidence interval = 1.01-2.64) compared with participants without any depressive symptoms. New-onset depressive symptoms increased the mortality risk (risk ratio = 2.37, 95% confidence interval = 1.52-3.69), but not CVD (risk ratio = 1.15, 95% confidence interval = 0.84-1.58). Remitted depressive symptoms were associated with a 35% and 13% excess risk of CVD and mortality, respectively. CONCLUSION: Persistent and remitted depressive symptoms were associated with an increased risk of CVD. New-onset depressive symptoms predicted elevated mortality risk.

8.
Food Res Int ; 127: 108628, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31882076

RESUMO

Perfluorodecanoic acid (PFDA) is a highly toxic food contaminant that is extensively used in food applications as surface antifouling agent. In this present study, we aimed to assess whether green tea polyphenols (GTPs) and epigallocatechin-3-gallate (EGCG) exert protective effects against PFDA-induced liver damage and inflammation in mice. A mouse model to evaluate liver toxicity was established by giving mice drinking water containing different concentrations of PFDA. GTPs or EGCG (0.32%, w/v) were co-administered to mice exposed to PFDA in drinking water. Overall, GTPs and EGCG extended the survival time and inhibited weight loss among mice who received a lower dose of PFDA. Moreover, GTPs and EGCG ameliorated hepatic oxidative stress, cell apoptosis, necrosis, steatosis, edema, and degeneration, reduced hepatic inflammation and NLRP3 inflammasome activation caused by a moderate dose of PFDA. Taken together, these results show that GTPs or EGCG (or green tea intake) supplements can be beneficial for people exposed to PFDA.

10.
JAMA Intern Med ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31329220

RESUMO

Importance: Accumulating epidemiologic evidence has suggested favorable associations between plant-based dietary patterns and risk of type 2 diabetes, although there is a lack of a quantitative summary of evidence substantiating this important association. Objective: To quantitatively synthesize available prospective observational evidence on the association between plant-based dietary patterns and risk of type 2 diabetes. Data Sources: A systematic search of PubMed and MEDLINE, Embase, Web of Science, and reference lists through February 15, 2019, was conducted. Data analysis was conducted between December 2018 and February 2019. Study Selection: All prospective observational studies that examined the association between adherence to plant-based dietary patterns and incidence of type 2 diabetes among adults 18 years or older were identified. Data Extraction and Synthesis: Meta-analysis of Observational Studies in Epidemiology guidelines for data abstraction and reporting were followed, and a National Heart, Lung, and Blood Institute assessment tool was used to evaluate study quality. Two authors independently conducted full-text assessments and data abstraction. Meta-analysis was conducted using the random-effects method to calculate the overall relative risk (RR) and 95% CI. Main Outcomes and Measures: Level of adherence to a plant-based diet and incidence of type 2 diabetes. Results: A total of 9 studies were identified, totaling 307 099 participants with 23 544 cases of incident type 2 diabetes. A significant inverse association was observed between higher adherence to a plant-based dietary pattern and risk of type 2 diabetes (RR, 0.77; 95% CI, 0.71-0.84) in comparison with poorer adherence, with modest heterogeneity across studies (I2 = 44.5%; P = .07 for heterogeneity). Similar findings were obtained when using the fixed-effects model (RR, 0.80; 95% CI, 0.75-0.84). Consistent associations were observed across predefined subgroups. This association was strengthened when healthy plant-based foods, such as fruits, vegetables, whole grains, legumes, and nuts, were included in the definition of plant-based patterns (RR, 0.70; 95% CI, 0.62-0.79). Most studies were deemed to have good quality in terms of dietary assessment, disease outcomes, and statistical adjustment for confounding factors. Using restricted cubic splines, a significant inverse linear dose-response association was identified between plant-based dietary indices and risk of type 2 diabetes. Conclusions and Relevance: Plant-based dietary patterns, especially when they are enriched with healthful plant-based foods, may be beneficial for the primary prevention of type 2 diabetes.

11.
Br J Cancer ; 121(2): 180-192, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31213659

RESUMO

BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.


Assuntos
Estatura , Índice de Massa Corporal , Genes BRCA1 , Genes BRCA2 , Heterozigoto , Análise da Randomização Mendeliana , Mutação , Neoplasias Ovarianas/etiologia , Adulto , Idoso , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Modelos de Riscos Proporcionais
12.
Food Funct ; 10(7): 3898-3908, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31187838

RESUMO

Inflammatory liver diseases present a significant public health problem. Green tea polyphenols (GTPs) have a myriad of health benefits in animals and humans, including alleviating of hepatic inflammation; however, the underlying mechanisms are complicated and remain unclear. The current study investigated the preventive effects and mechanism of GTPs on lipopolysaccharide (LPS)-induced inflammatory liver injury in mice. The ICR mice received intragastric GTPs once per day for 7 consecutive days prior to LPS stimulation (15 mg kg-1, intraperitoneally) and liver damage and oxidative stress, pro-inflammatory cytokines, and the hepatic nuclear factor-κB (NF-κB) and Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasomes were observed. Our results showed that GTP supplementation significantly reduced LPS-induced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic malondialdehyde (MDA) levels; and LPS-induced reduction of glutathione (GSH) levels and total superoxide dismutase (T-SOD) activities was drastically improved by GTP pretreatment. GTP supplementation significantly reduced plasma contents and hepatic mRNA levels of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α, compared with LPS-treated mice which did not receive GTP treatment. In addition, the production of cytokines, such as IL-1ß, IL-18, IL-6, and TNF-α in mice livers, and acute-phase response (plasma levels of nitric oxide and C-reactive protein) were also decreased following GTP pre-treatment. Furthermore, GTPs reduced LPS-induced hepatic NF-κB signaling and NLRP3 inflammasome activation. GTPs exert protective effects against inflammatory liver injury by regulating NF-κB signaling and the NLRP3 inflammasome activation. Our findings suggest that dietary GTP supplementation may be an adjunctive prevention and treatment for acute liver injury-associated inflammation.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Inflamassomos/antagonistas & inibidores , Lipopolissacarídeos/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Chá/química , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase
13.
J Natl Cancer Inst ; 111(4): 350-364, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30312457

RESUMO

BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Estatura , Índice de Massa Corporal , Neoplasias da Mama/etiologia , Análise da Randomização Mendeliana , Mutação , Adulto , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Risco
14.
J Agric Food Chem ; 66(29): 7674-7683, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29969892

RESUMO

Theanine, a unique bioactive constituent from tea ( Camellia sinensis) leaves, is widely used as a functional ingredient and dietary supplement. To evaluate the anti-inflammatory and hepatoprotective effects of theanine and its molecular mechanism, the lipopolysaccharide (LPS)-induced inflammation mouse model was employed in this study. The survival rate of mice in the theanine-treated group increased significantly compared with that of LPS-only group mice. Furthermore, ICR male mice were randomly divided into three or four groups: control, LPS (LPS treatment only), LPS + theanine (20 mg/kg/day), and theanine (theanine treatment only). The results showed that compared with the LPS group, the liver damage and oxidative stress of the theanine-treated group decreased significantly, based on plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, hepatic total superoxide dismutase (T-SOD), and malondialdehyde (MDA) levels, and histological scores and apoptosis [terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase-3 activity] in the liver tissues. Furthermore, compared with no treatment, pretreatment with theanine significantly decreased the release of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, inhibited the expression of several inflammatory factors (including IL-1ß, TNF-α, and IL-6), and increased the IL-10/interferon (IFN)-γ ratio in the hepatic tissues. In the LPS-induced inflammation model, theanine inhibited the expression of proinflammatory mediators involved in the nuclear factor-kappa B (NF-κB) pathway, such as inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3), and attenuated the phosphorylation of NF-κB in the hepatic tissues. Moreover, theanine suppressed the acute-phase response (elevated nitric oxide and C-reactive protein levels). Furthermore, theanine suppressed the LPS-induced inflammatory state by normalizing hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Taken together, the results suggest that theanine potentially ameliorates LPS-induced inflammation and acute liver injury; molecular mechanism of action may involve normalization of HPA axis hyperactivity and inactivation of the NF-κB signaling pathway.


Assuntos
Glutamatos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Hepatopatias/imunologia , Hepatopatias/prevenção & controle , Doença Aguda/terapia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/sangue , Hepatopatias/etiologia , Masculino , Malondialdeído/imunologia , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/imunologia
15.
Breast Cancer Res Treat ; 168(3): 703-712, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29302764

RESUMO

BACKGROUND: Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. METHODS: We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). RESULTS: Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). CONCLUSIONS: We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Prognóstico , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/patologia , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Nigéria/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco
16.
Food Funct ; 8(9): 3165-3177, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28782772

RESUMO

Alcohol intake is a major risk factor for the pathogenesis of alcoholic liver diseases. Accumulating evidence suggests that green tea protects against alcoholic liver injury; however, the underlying mechanisms remain unclear. The present study investigated the role of endothelial nitric oxide synthase (eNOS) in the protective effects of green tea against alcohol-induced liver injury and inflammation. Ethanol was intragastrically administered to male C57BL/6 mice once a day, and the mice were allowed free access to green tea infusion or water for two weeks. We assessed the plasma levels of alanine aminotransferase and aspartate aminotransferase, hepatic contents of thiobarbituric acid reactive substances, malondialdehyde and triglyceride and hepatic mRNA expression of pro-inflammatory cytokines (interleukin-1ß, tumor necrosis factor-α, and interleukin-6). Our results showed that compared with water alone, green tea infusion markedly reduced liver damage, hepatic oxidative stress, hepatic lipid accumulation and inflammatory response. Green tea infusion also significantly reduced hepatic nuclear factor-κB expression and its downstream inflammatory mediators (inducible nitric oxide synthase and cyclooxygenase-2) mRNA levels in ethanol-treated mice. Additionally, green tea infusion significantly activated hepatic phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt), which are associated with the upregulation of phosphorylated eNOS expression and the increase of plasma nitric oxide levels in ethanol-treated mice. Furthermore, the protective effects of green tea infusion were considerably inhibited by the eNOS inhibitor NG-nitro-l-arginine methyl ester in ethanol-treated mice. In conclusion, our study demonstrated that the protective effects of green tea infusion on alcohol-induced liver injury and inflammation involve the modulation of the PI3K/AKT/eNOS pathway.


Assuntos
Camellia sinensis/química , Hepatopatias Alcoólicas/prevenção & controle , Óxido Nítrico Sintase Tipo III/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Preparações de Plantas/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/imunologia , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Etanol/efeitos adversos , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo III/genética , Fosfatidilinositol 3-Quinases/genética , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/genética , Chá/química
17.
Asia Pac J Clin Nutr ; 26(3): 384-391, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28429900

RESUMO

For thousands of years, humans have consumed tea made from leaves of Camellia sinensis, first as a medicinal herb and then as a widely popular beverage. In the past 10 years, theanine, a tea-derived, unique, nonproteinic amino acid, has been extensively studied for its health benefits. Recently, multiple lines of evidence have proven its beneficial effects on hepatic and immune functions. One possible mechanism for its biological activity involves the downregulation of the inflammatory response through the induction of nitric oxide production and glutathione synthesis. In this review, we summarize published results describing the potential mechanisms for these beneficial health effects and provide new insight into how theanine can be therapeutic for liver injury and chronic liver disease.


Assuntos
Camellia sinensis/química , Glutamatos/administração & dosagem , Hepatopatias/prevenção & controle , Extratos Vegetais/administração & dosagem , Chá/química , Disponibilidade Biológica , Glutamatos/farmacocinética , Glutamatos/uso terapêutico , Promoção da Saúde , Humanos , Fatores Imunológicos , Extratos Vegetais/uso terapêutico , Folhas de Planta
18.
Sci Rep ; 6: 38937, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27958337

RESUMO

Sarcopenia is a condition characterized by progressive and generalized loss of skeletal muscle mass and function. In this study, we used a cross-sectional study with 1090 community-dwelling Chinese citizens aged 60 years and older to evaluate the association of type 2 diabetes mellitus (T2DM) with the risk of sarcopenia and pre-sarcopenia. Sarcopenia was defined using the Asian Working Group for Sarcopenia (AWGS) criteria that include both muscle mass and muscle function/physical activity. Pre-sarcopenia was defined as having low skeletal muscle index but with normal muscle/physical activity. The prevalence of sarcopenia and pre-sarcopenia was significantly higher in T2DM patients than in healthy controls (14.8% vs. 11.2%, p = 0.035 for sarcopenia, and 14.4% vs. 8.4%, p = 0.002 for pre-sarcopenia). In multivariate logistic regression analyses adjusting by age, gender, anti-diabetic medication, energy intake, protein intake, physical activity, and visceral fat area, we found that Chinese elderly with T2DM exhibited significantly increased risks of sarcopenia (OR = 1.37, 95% CI = 1.02-2.03) and pre-sarcopenia (OR = 1.73, 95% CI = 1.10-2.83) compared to non-diabetic individuals. This is the first study to evaluate the association of T2DM with the risks of sarcopenia and pre-sarcopenia in China. Among a group of community-dwelling Chinese elderly, T2DM was significantly associated with increased risks of sarcopenia and pre-sarcopenia.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Sarcopenia/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcopenia/etiologia
20.
Hum Genet ; 135(10): 1145-59, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27380242

RESUMO

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.


Assuntos
Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Receptor alfa de Estrogênio/genética , MicroRNAs/genética , Ribonuclease III/genética , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
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