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1.
Oncogene ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034306

RESUMO

Cancer metabolism research has recently been revived and its focus expanded from glucose and the Warburg's effects on other nutrients, such as glutamine. The underlying mechanism of oncogenic alterations of glutaminolysis remains unclear. Genetic alterations of EGFR are observed in ~50% of glioblastoma (GBM) patients, and have been found to play important roles in the metabolic abnormalities of GBM. In this study, we found that glutamine metabolism was upregulated after EGFR activation in a GDH1 (glutamate dehydrogenase 1)-dependent manner. Knockdown of GDH1 significantly reduced the cell proliferation, colony formation and tumorigenesis abilities of glioblastoma cells. Furthermore, we showed that GDH1-mediated glutaminolysis was involved in EGF-promoted cell proliferation. EGFR triggered the phosphorylation of ELK1 at Ser 383 through activating MEK/ERK signaling. Phosphorylated ELK1 enriched in the promoter of GDH1 to activate the transcription of GDH1, which then promoted glutamine metabolism. In addition, EGFR activation did not accelerate glutaminolysis in ELK1 knockdown or ELK1 Ser383-mutated cells. Collectively, our findings indicate that EGFR phosphorylates ELK1 to activate GDH1 transcription and glutaminolysis through MEK/ERK pathway, providing new insight into oncogenic alterations of glutamine metabolism.

2.
BMJ ; 368: l6669, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915124

RESUMO

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estilo de Vida Saudável/fisiologia , Expectativa de Vida , Neoplasias , Comportamento de Redução do Risco , Adulto , Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/psicologia , Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Neoplasias/psicologia , Pesquisa em Enfermagem , Estudos Prospectivos , Fumar
3.
Artigo em Inglês | MEDLINE | ID: mdl-31802116

RESUMO

CONTEXT: Eating habits and food craving are strongly correlated with weight status. It is currently not well understood how psychological and behavioral factors influence both weight loss and weight regain. OBJECTIVE: To examine the associations between psychological and behavioral predictors with weight changes and energy intake in a randomized controlled trial on weight loss. DESIGN AND SETTING: The Prevention of Obesity Using Novel Dietary Strategies (POUNDSLOST) is a dietary intervention trial, which examined the efficacy of four diets on weight loss over 2 years. Participants were 811 overweight (BMI: 25-40.9 kg/m2, age: 30-70 years) otherwise healthy adults. RESULTS: Every 1-point increase in craving score for high-fat foods at baseline was associated with greater weight loss (-1.62kg, P=0.0004) and a decrease in energy intake (r = -0.10, P =0.01) and fat intake (r = -0.16, P <0.0001) during the weight loss period. In contrast, craving for carbohydrates/starches was associated with both less weight loss (P <0.0001) and more weight regain (P =0.04).Greater cognitive restraint of eating at baseline was associated with both less weight loss (0.23kg, P <0.0001) and more weight regain (0.14kg, P =0.0027) whereas greater disinhibition of eating was only associated with more weight regain (0.12kg, P =0.01). CONCLUSIONS: Craving for high-fat foods is predictive of greater weight loss while craving for carbohydrates is predictive of less weight loss. Cognitive restraint is predictive of less weight loss and more weight regain. Interventions targeting different psychological and behavioral factors can lead to greater success in weight loss.

4.
Med Ultrason ; 21(4): 441-448, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31765453

RESUMO

AIM: Studies on the usefulness of speckle tracking echocardiography (STE) in the evaluation of the left ventricle in rats with stress cardiomyopathy (SCM) are limited. Our aim was to investigate whether strain values by STE and cardiac troponin I (cTnI) could predict early myocardial injury in rats with SCM. MATERIAL AND METHODS: SCM was induced in Sprague-Dawley female rats using immobilization (IMO) stress. Biomarkers and echocardiographic parameters were evaluated and compared among groups (group 1 - 30 minutes after IMO stress, group 2 - 24 hours after IMO stress, and control group). We defined myocardial injury as a left ventricular ejection fraction <50%. Possible predictors of early myocardial injury were determined by univariate logistic regression, and independent predictors of early myocardial injury were investigated with multivariable logistic regression. RESULTS: A total of 44 rats with a mean weight of 426±33 g were evaluated. Group 1 had the highest plasma epinephrine and norepinephrine levels (p<0.001) and the highest heart rate (p<0.001). In univariate logistic regression, cTnI (OR=2.61 [1.02‒10.25], p=0.043) and global longitudinal strain (GLS) (OR=2.13 [1.12‒6.26], p=0.022) were predictive of early myocardial injury. When GLS and cTnI were included in a multivariate analysis, only GLS remained an independent predictor of early myocardial injury (OR=2.67 [1.14‒14.76], p=0.027). CONCLUSIONS: STE is useful for the quantitative detection of subtle myocardial abnormalities in rats with SCM. GLS may provide a reliable and non-invasive method to predict early myocardial injury.

5.
Nano Lett ; 19(12): 8381-8387, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31665887

RESUMO

We report on the emergent magnetic state of (111)-oriented CoCr2O4 ultrathin films sandwiched between Al2O3 spacer layers in a quantum confined geometry. At the two-dimensional crossover, polarized neutron reflectometry reveals an anomalous enhancement of the total magnetization compared to the bulk value. Synchrotron X-ray magnetic circular dichroism measurements demonstrate the appearance of a long-range ferromagnetic ordering of spins on both Co and Cr sublattices. Brillouin function analyses and ab-initio density functional theory calculations further corroborate that the observed phenomena are due to the strongly altered magnetic frustration invoked by quantum confinement effects, manifested by the onset of a Yafet-Kittel-type ordering as the magnetic ground state in the ultrathin limit, which is unattainable in the bulk.

6.
Nano Lett ; 19(11): 8311-8317, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31644875

RESUMO

Artificial complex-oxide heterostructures containing ultrathin buried layers grown along the pseudocubic [111] direction have been predicted to host a plethora of exotic quantum states arising from the graphene-like lattice geometry and the interplay between strong electronic correlations and band topology. To date, however, electronic-structural investigations of such atomic layers remain an immense challenge due to the shortcomings of conventional surface-sensitive probes with typical information depths of a few angstroms. Here, we use a combination of bulk-sensitive soft X-ray angle-resolved photoelectron spectroscopy (SX-ARPES), hard X-ray photoelectron spectroscopy (HAXPES), and state-of-the-art first-principles calculations to demonstrate a direct and robust method for extracting momentum-resolved and angle-integrated valence-band electronic structure of an ultrathin buckled graphene-like layer of NdNiO3 confined between two 4-unit cell-thick layers of insulating LaAlO3. The momentum-resolved dispersion of the buried Ni d states near the Fermi level obtained via SX-ARPES is in excellent agreement with the first-principles calculations and establishes the realization of an antiferro-orbital order in this artificial lattice. The HAXPES measurements reveal the presence of a valence-band bandgap of 265 meV. Our findings open a promising avenue for designing and investigating quantum states of matter with exotic order and topology in a few buried layers.

7.
J Assist Reprod Genet ; 36(11): 2357-2366, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31650454

RESUMO

PURPOSE: Psychological stress exists widely in modern society and results in the disruption of testicular tight junctions, germ cell apoptosis, and the disorder of fertility hormones and even causes infertility. Ghrelin (GHRL), a 28-amino acid peptide secreted mainly by the stomach and pancreas, has been reported to alleviate male reproductive injury through inhibiting apoptosis. However, whether GHRL has a beneficial effect on psychological stress-induced testicular injury and the possible mechanisms remain poorly understood. METHODS: Male mice were immobilized in Decapicone bags for 3 h daily for 14 days treated with or without GHRL (i.p. 100 mg/kg body weight). Body weight and testicular weight were measured. Histological alterations and apoptosis were examined by H.E. staining and TUNEL staining, respectively. The expression of endoplasmic reticulum (ER) stress markers, inflammatory cytokines, Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) in the testes was investigated. RESULTS: Exposure to stress caused testicular histological alterations, an elevation of the Johnsen score, and germ cell apoptosis, while GHRL partially alleviated the adverse effects. The expression of ER stress marker proteins, including GRP78, CHOP, ATF6, p-JNK, and XBP-1, was upregulated in the stress group; however, GHRL treatment significantly suppressed the activation of ER stress in the testes. GHRL also inhibited the expression of TNF-α, IL-1ß, IL-6, IL-10, TLR4, and NF-κB. CONCLUSIONS: GHRL alleviated testicular injury induced by ER stress and inflammation which is associated with the TLR4/NF-κB signaling pathway, and these findings may provide a novel strategy for preventing and treating reproductive dysfunction.

8.
Proc Natl Acad Sci U S A ; 116(40): 19863-19868, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31527227

RESUMO

We investigate [Formula: see text]/[Formula: see text] superlattices in which we observe a full electron transfer at the interface from Ir to Ni, triggering a massive structural and electronic reconstruction. Through experimental characterization and first-principles calculations, we determine that a large crystal field splitting from the distorted interfacial [Formula: see text] octahedra surprisingly dominates over the spin-orbit coupling and together with the Hund's coupling results in the high-spin (S = 1) configurations on both the Ir and Ni sites. This demonstrates the power of interfacial charge transfer in coupling lattice, charge, orbital, and spin degrees of freedom, opening fresh avenues of investigation of quantum states in oxide superlattices.

9.
Anal Chem ; 91(19): 12560-12567, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31487155

RESUMO

Signaling proteins exemplified by calmodulin usually bind cooperatively to multiple ligands. Intermediate states and allosteric behavior are difficult to characterize. Here we extend a recently reported mass spectrometry (MS)-based method named LITPOMS (ligand titration, fast photochemical oxidation of proteins and mass spectrometry) that characterizes complex binding systems typically found as signaling proteins. As reported previously, calmodulin's response to binding four Ca2+ can be determined by LITPOMS to reveal binding sites, binding order, and most importantly composite binding behavior. Modeling this behavior provides site-specific binding affinities. In this article, we dissect the composite, peptide-level conformational changes at several regions either by digestion with a different protease or by tandem MS of LITPOMS behavior at the amino-acid residue level. Such dissection greatly elevates spatial resolution and increases the confidence of binding-order assignment. These complementary views of complex protein conformational change recapitulate the cumulative understanding via a single approach, providing new insights on poorly understood yet important allostery and underpin an approach applicable for exploring other signaling systems.

10.
Nutr Metab Cardiovasc Dis ; 29(10): 1040-1049, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31377179

RESUMO

BACKGROUND AND AIMS: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). METHODS AND RESULTS: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). CONCLUSION: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639.

11.
Anal Chem ; 91(14): 9238-9245, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31241913

RESUMO

Fast photochemical oxidation of protein (FPOP) has become an important mass spectrometry-based protein footprinting approach. Although the hydroxyl radical (•OH) generated by photolysis of hydrogen peroxide (H2O2) is most commonly used, the pathways for its reaction with amino-acid side chains remain unclear. Here, we report a systematic study of •OH oxidative modification of 13 amino acid residues by using 18O isotopic labeling. The results differentiate three classes of residues on the basis of their oxygen uptake preference toward different oxygen sources. Histidine, arginine, tyrosine, and phenylalanine residues preferentially take oxygen from H2O2. Methionine residues competitively take oxygen from H2O2 and dissolved oxygen (O2), whereas the remaining residues take oxygen exclusively from O2. Results reported in this work deepen the understanding of •OH labeling pathway on a FPOP platform, opening new possibilities for tailoring FPOP conditions in addressing many biological questions in a profound way.

12.
Anal Chem ; 91(9): 5508-5512, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30963760

RESUMO

We found that a newly developed method named LITPOMS (ligand titration, fast photochemical oxidation of proteins and mass spectrometry) can characterize section-by-section of a protein the conformational changes induced by metal-ion binding. Peptide-level LITPOMS applied to Ca2+ binding to calmodulin reveals binding order and site-specific affinity, providing new insights on the behavior of proteins upon binding Ca2+. We established that EF hand-4 (EF-4) binds calcium first, followed by EF-3, EF-2, and EF-1 and determined the four affinity constants by modeling the extent-of-modification curves. We also found positive cooperativity between EF-4, EF-3 and EF-2, EF-1 and allostery involving the four EF-hands. LITPOMS recapitulates via one approach the calcium-calmodulin binding that required decades of sophisticated development to afford versatility, comprehensiveness, and outstanding spatial resolution.

13.
Technol Cancer Res Treat ; 18: 1533033819828709, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786836

RESUMO

BACKGROUND: MicroRNAs contribute to chemotherapy response in different types of cancer. We hypothesized that plasma miRNAs are potentially associated with chemotherapy response in patients with metastatic breast cancer. PATIENTS AND METHODS: Fourteen candidate microRNAs were chosen from the literature, and their plasma levels were measured by quantitative polymerase chain reaction (PCR). Forty metastatic breast cancer patients were chosen as the training groups. The potential significant microRNAs were validated in another 103 plasma samples. RESULTS: In the training set, we identified 3 microRNAs (miR-200a, miR-210, and miR-451) as significantly dysregulated miRNAs between sensitive group (partial response (and stable disease) and resistant group (progressive disease). Then, in the validation set, miR-200a (area under the curve = 0.881, sensitivity = 94.1%, specificity = 76.7%) and miR-210 (area under the curve = 0.851, sensitivity = 88.2%, specificity = 72.1%) showed high diagnostic accuracy for distinguishing sensitive group from resistant group. Furthermore, the plasma level of miR-200a was significantly associated with the stage in surgery ( P = .035), and the high level of miR-210 expression was associated with internal organ metastasis (liver, lung, and brain; P = .024). CONCLUSIONS: Plasma miR-200a and miR-210 could be effective biomarkers for the prediction of chemotherapy resistance in metastatic breast cancer patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/sangue , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Estudos de Casos e Controles , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Prognóstico , Curva ROC
14.
Sci Rep ; 9(1): 1896, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760747

RESUMO

Generally, lattice distortions play a key role in determining the electronic ground states of materials. Although it is well known that trigonal distortions are generic to most two dimensional transition metal dichalcogenides, the impact of this structural distortion on the electronic structure and topological properties has not been understood conclusively. Here, by using a combination of polarization dependent X-ray absorption spectroscopy (XAS), X-ray photoelectron spectroscopy (XPS) and atomic multiplet cluster calculations, we have investigated the electronic structure of titanium dichalcogenides TiX2 (X = S, Se, Te), where the magnitude of the trigonal distortion increase monotonically from S to Se and Te. Our results reveal the presence of an anomalously large crystal field splitting. This unusual kind of crystal field splitting is likely responsible for the unconventional electronic structure of TiX2 compounds and ultimately controls the degree of the electronic phase protection. Our findings also indicate the drawback of the distorted crystal field picture in explaining the observed electronic ground state and emphasize the key importance of trigonal symmetry, metal-ligand hybridization and electron-electron correlations in defining the electronic structures at the Fermi energy.

15.
J Am Soc Mass Spectrom ; 30(2): 213-217, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30484077

RESUMO

We report a novel method named LITPOMS (ligand titration, fast photochemical oxidation of proteins and mass spectrometry) to characterize protein-ligand binding stoichiometry, binding sites, and site-specific binding constants. The system used to test the method is melittin-calmodulin, in which the peptide melittin binds to calcium-bound calmodulin. Global-level measurements reveal the binding stoichiometry of 1:1 whereas peptide-level data coupled with fitting reveal the binding sites and the site-specific binding affinity. Moreover, we extended the analysis to the residue level and identified six critical binding residues. The results show that melittin binds to the N-terminal, central linker, and C-terminal regions of holo-calmodulin with an affinity of 4.6 nM, in agreement with results of previous studies. LITPOMS, for the first time, brings high residue-level resolution to affinity measurements, providing simultaneously qualitative and quantitative understanding of protein-ligand binding. The approach can be expanded to other binding systems without tagging the protein to give high spatial resolution. Graphical Abstract.


Assuntos
Espectrometria de Massas/métodos , Fotoquímica/métodos , Proteínas/análise , Proteínas/metabolismo , Sítios de Ligação , Cálcio/metabolismo , Calmodulina/metabolismo , Ligantes , Meliteno/metabolismo , Oxirredução , Proteínas/química
16.
Am J Cancer Res ; 8(9): 1873-1886, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323979

RESUMO

Through next generation sequencing, this study evaluated the circulating tumor DNA (ctDNA) of advanced breast cancer patients to prospectively explore the relationship between specific DNA mutations and prognosis as well as therapeutic decision making. The target region covered 1021 gene totally. Clinical characteristics, treatment and outcome data were collected. We analyzed progression-free survival (PFS) from first-line therapy and overall survival (OS), and found that their endpoints were correlated with observed gene mutations. We enrolled 54 patients, with a median follow-up time of 8 years. Mutations were found in TP53, PIK3CA, and ERBB family, at 40.7%, 35.2%, and 25.9%, respectively. PIK3CA more frequently occurred in the site of 3140 A>G (p.H1047R) for 20.4% and HER2+ diseases, and it was associated with shorter median PFS and worse OS among HER2+ patients [mutant vs. wild type: 4 (range 2-9) vs. 8 (range 2-22) months, P=0.006], and [mutant vs. wild type: 29 (range 12-74) vs. 64 (range 20-96) months, P=0.043], respectively. The patients with mutations in TP53 had shorter OS (median 64 vs. 121 months, P=0.006). Multivariate analysis for HER2+ disease demonstrated that the PIK3CA p.H1047R mutation was the only factor associated with shorter PFS (P=0.025); while the receiver operating characteristic (ROC) analysis produces an area under the curve (AUC) of 0.789. The ctDNA analysis, found PIK3CA p.H1047R mutation was more frequent in HER2+ disease and associated with worse OS. It was also the only mutation associated with shorter PFS through a multivariate analysis of HER2+ patients who were treated with trastuzumab, suggesting trastuzumab had lower activity in these patients. The presence of a TP53 mutation was associated with worse OS.

17.
J Nutr ; 148(11): 1821-1829, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30247611

RESUMO

Background: The relation between dietary fat intake and body weight remains controversial. Few studies have examined long-term changes in types of dietary fat and weight change in longitudinal studies. Objective: The objective of this study was to examine associations between intake of different types of fat and long-term weight change in US women and men. Methods: The association between changes in consumption of varying types of fat and weight change was examined every 4 y through the use of multivariate models adjusted for age, baseline body mass index, and change in percentage energy from protein, intake of cereal fiber, fruits, and vegetables, alcohol use, and other lifestyle covariates in 3 prospective US cohorts, including 121,335 men and women free of diabetes, cardiovascular disease, cancer, or obesity over a 20- to 24-y follow-up. Dietary intakes and body weight were assessed via validated questionnaires. Cohort-specific results were pooled with the use of a random-effect meta-analysis. Results: Compared with equivalent changes in carbohydrate intake, a 5% increase in energy from saturated fatty acid (SFA) and a 1% increase in energy from trans-fat were associated with 0.61 kg (95% CI: 0.54, 0.68 kg) and 0.69 kg (95% CI: 0.56, 0.84 kg) greater weight gain per 4-y period, respectively. A 5% increase in energy from polyunsaturated fatty acid (PUFA) was associated with less weight gain (-0.55 kg; 95% CI: -0.81, -0.29 kg). Increased intake of monounsaturated fatty acid (MUFA) from animal sources by 1% was associated with weight gain of 0.29 kg (95% CI: 0.25, 0.33 kg), whereas MUFA from plant sources was not associated with weight gain. Conclusions: Different dietary fats have divergent associations with long-term weight change in US men and women. Replacing saturated and trans-fats with unsaturated fats, especially PUFAs, contributes to the prevention of age-related weight gain. These trials were registered at clinicaltrials.gov as NCT00005152 and NCT00005182.


Assuntos
Inquéritos sobre Dietas , Gorduras na Dieta/classificação , Ganho de Peso , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Estados Unidos
18.
Chin J Cancer Res ; 30(3): 315-326, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30046226

RESUMO

Objective: Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis. Circulating tumor cells (CTCs) are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival (PFS) is controversial. We aim to verify their predictive value in TNBC. Methods: In present prospective cohort study, we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC (taken at inclusion in this study) and analyzed correlations between CTC numbers and outcomes and other clinical parameters. Results: Median PFS was 6.0 (range: 1.0-25.0) months for the entire cohort, in whom we found no correlations between baseline CTC status and initial tumor stage (P=0.167), tumor grade (P=0.783) or histological type (P=0.084). However, among those getting first-line treatment, baseline CTC status was positively correlated with ratio of peripheral natural killer (NK) cells (P=0.032), presence of lung metastasis (P=0.034) and number of visceral metastatic site (P=0.037). Baseline CTC status was predictive for PFS in first-line TNBC (P=0.033), but not for the cohort as a whole (P=0.118). This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration (P=0.049). Conclusions: Baseline CTC status was predictive of lung metastasis, peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment. We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

19.
J Nutr ; 148(5): 721-728, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30053283

RESUMO

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively). Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.


Assuntos
Colesterol/sangue , Colesterol/metabolismo , Gorduras Insaturadas na Dieta/farmacologia , Síndrome Metabólica/metabolismo , Óleo de Brassica napus/farmacologia , Células THP-1/efeitos dos fármacos , Estudos Cross-Over , Dieta , Gorduras Insaturadas na Dieta/administração & dosagem , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Óleo de Brassica napus/administração & dosagem , Células THP-1/fisiologia
20.
Circulation ; 138(4): 345-355, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29712712

RESUMO

BACKGROUND: Americans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population. METHODS: Using data from the Nurses' Health Study (1980-2014; n=78 865) and the Health Professionals Follow-up Study (1986-2014, n=44 354), we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m2, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%), and estimated hazard ratios for the association of total lifestyle score (0-5 scale) with mortality. We used data from the NHANES (National Health and Nutrition Examination Surveys; 2013-2014) to estimate the distribution of the lifestyle score and the US Centers for Disease Control and Prevention WONDER database to derive the age-specific death rates of Americans. We applied the life table method to estimate life expectancy by levels of the lifestyle score. RESULTS: During up to 34 years of follow-up, we documented 42 167 deaths. The multivariable-adjusted hazard ratios for mortality in adults with 5 compared with zero low-risk factors were 0.26 (95% confidence interval [CI], 0.22-0.31) for all-cause mortality, 0.35 (95% CI, 0.27-0.45) for cancer mortality, and 0.18 (95% CI, 0.12-0.26) for cardiovascular disease mortality. The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6-66.7) for all-cause mortality, 51.7% (95% CI, 37.1-62.9) for cancer mortality, and 71.7% (95% CI, 58.1-81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3-29.8) for women and 25.5 years (95% CI, 24.7-26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3-44.9) for women and 37.6 years (95% CI, 35.8-39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8-16.2) longer among female Americans with 5 low-risk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1-14.2). CONCLUSIONS: Adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults.


Assuntos
Pessoal de Saúde , Estilo de Vida Saudável , Expectativa de Vida , Comportamento de Redução do Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Causas de Morte , Bases de Dados Factuais , Exercício , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , não Fumantes , Enfermeiras e Enfermeiros , Inquéritos Nutricionais , Fatores de Proteção , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
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