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1.
Br J Nutr ; : 1-35, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34526168

RESUMO

Chronic inflammation exerts pleiotropic effects in the etiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HRs) as well as 95% confidence intervals (95% CIs) for the risk of incident COPD. During a median follow-up of 8.96 years (interquartile range 8.29 to 9.53 years), 9016 new-onset events of COPD were documented. We found that regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0.80 (95% CI, 0.75 to 0.85; P<0.001). When subgroup analyses were performed by smoking status, the adjusted HRs for the association of regular glucosamine use with incident COPD were 0.84 (0.73 to 0.96), 0.84 (0.77 to 0.92), and 0.71 (0.62 to 0.80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (P for interaction=0.078). Incident COPD could be reduced by 14% to 84% through a combination of regular glucosamine use and smoking cessation.

2.
Eur J Endocrinol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524977

RESUMO

Objective To examine the association of incident type 2 diabetes (T2D) risk with sleep factors, genetic risk, and their combination effects. Design Large prospective population-based cohort study. Methods This population-based prospective cohort study included 360 403 (mean [SD] age: 56.6 [8.0] years) participants without T2D at baseline from the UK Biobank. Genetic risk was categorized as high (highest quintile), intermediate (quintiles 2 to 4), and low (lowest quintile) based on a polygenic risk score for T2D. Sleep scores, including long or short sleep duration, insomnia, snoring, late chronotype, and excessive daytime sleepiness, were categorized as an unfavourable, intermediate, or favourable sleep and circadian pattern. Results During a median follow-up of 9.0 years, 13 120 incident T2D cases were recorded. Among the participants with an unfavourable sleep and circadian pattern, 6.96% (95% CI, 6.68%-7.24%) developed T2D versus 2.37% (95% CI, 2.28%-2.46%) of participants with a favourable sleep and circadian pattern (adjusted HR: 1.53, 95% CI: 1.45-1.62). Of participants with a high genetic risk, 5.53% (95% CI, 5.36%-5.69%) developed T2D versus 2.01% (95% CI, 1.91%-2.11%) of participants with a low genetic risk (adjusted HR: 2.89, 95% CI: 2.72-3.07). The association with sleep and circadian patterns was independent of genetic risk strata. Participants in the lowest quintile with an unfavourable sleep and circadian pattern were 3.97-fold more likely to develop T2D than those in the lowest quintile with a favourable sleep and circadian pattern. Conclusions Sleep and circadian patterns and genetic risk were independently associated with incident T2D. These results indicate the benefits of adhering to a healthy sleep and circadian pattern in entire populations, independent of genetic risk.

3.
Int J Med Sci ; 18(15): 3533-3543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522180

RESUMO

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.


Assuntos
COVID-19/complicações , Hipercolesterolemia/complicações , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/uso terapêutico , Aterosclerose/fisiopatologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/terapia , Membrana Celular/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Endocitose , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/terapia , Inflamação , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Prognóstico , SARS-CoV-2 , Receptores Depuradores Classe B/metabolismo
4.
Ann Am Thorac Soc ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242153

RESUMO

RATIONALE: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease 2019 (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of pre-existing COPD is unknown. OBJECTIVES: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. METHODS: We constructed a polygenic risk score (PRS) for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. RESULTS: Of 430,582 participants, 712 participants developed severe COVID-19 as of February 22, 2021, of whom 19.8% had pre-existing COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (OR, 1.34; 95% CI, 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. CONCLUSIONS: The PRS which combines multiple risk alleles can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of pre-existing COPD.

5.
Eur Respir J ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172472

RESUMO

BACKGROUND: Genetic and smoking contribute to chronic obstructive pulmonary disease (COPD), but whether a combined polygenic risk score (PRS) is associated with incident COPD and whether it has a synergistic effect on the smoking remains unclear. We aimed to investigate the association of PRS with COPD and explore whether smoking behaviors could modify such association. METHODS: Multivariable Cox proportional models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of the PRS and smoking with COPD. RESULTS: The study included 439 255 participants (mean age 56.5; 53.9% female), with a median follow-up of 9.0 years. The PRSlasso containing 2.5 million variants showed better discrimination and a stronger association for incident COPD than the PRS279 containing 279 genome-wide significance variants. Compared with the low genetic risk, the HRs of the medium and high genetic risk were 1.39 (95% CI, 1.31-1.48) and 2.40 (95% CI, 2.24-2.56), respectively. The HR of high genetic risk and current smoking was 11.62 (95% CI, 10.31-13.10) times of low genetic risk and never smoking. There were significant interactions between the PRSlasso and smoking status for incident COPD (p for interaction<0.001). From low genetic risk to high genetic risk, the HRs of current smoking increased from 4.32 (95% CI, 3.69-5.06) to 6.89 (95% CI, 6.21-7.64), and the population-attributable risks of smoking increased from 42.7% to 61.1%. CONCLUSION: PRS constructed from millions of variants below genome-wide significance showed significant associations with incident COPD. Participants with a high genetic risk may be more susceptible to developing COPD when exposed to smoking.

6.
Front Immunol ; 12: 589095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995341

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.


Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Pandemias , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina/epidemiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/fisiopatologia , Humanos
7.
Mar Pollut Bull ; 167: 112292, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33873041

RESUMO

The effects of multiple natural and anthropogenic stressors on the functional trait composition and diversity of marine macrobenthic communities in Laoshan Bay were investigated using biological trait analysis (BTA). Seven traits, including 27 trait modalities and four functional diversity indices (functional richness, functional evenness, functional divergence, and Rao's quadratic entropy), were considered. The results of RLQ (environmental variables (R), species taxa (L), and traits (Q)) and variance partitioning analysis (VPA) showed that the trait compositions and functional diversity of macrobenthic communities were influenced by a combination of stressors, among which heavy metals were the major factors. At the sites with high heavy metal pollution, the prevalent traits were infauna, burrower, and deposit feeder, whereas epifauna, carnivores and crawlers were dominant at the sites of low heavy metal contamination. The impact of natural environmental gradients on macrobenthic communities is also worthy of attention.


Assuntos
Invertebrados , Metais Pesados , Animais , Baías , Biodiversidade , China , Ecossistema , Monitoramento Ambiental , Metais Pesados/análise
8.
J Cachexia Sarcopenia Muscle ; 12(2): 350-357, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33527771

RESUMO

BACKGROUND: Candidate genes of neuromuscular junction (NMJ) pathway increased risk of frailty, but the extent and whether can be offset by exercises was unclear. The aim of this study was to investigate the association between aerobic exercises and incident frailty regardless of NMJ pathway-related genetic risk. METHODS: A cohort study on participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2011. A total of 7006 participants (mean age of 80.6 ± 10.3 years) without frailty at baseline were interviewed to record aerobic exercise status, and 4053 individuals among them submitted saliva samples. NMJ pathway-related genes were genotyped and weighted genetic risk scores were constructed. RESULTS: During a median follow-up of 3.1 years (19 634 person-years), there were 1345 cases (19.2%) of incident frailty. Persistent aerobic exercises were associated with a 26% lesser frailty risk [adjusted hazard ratio (HR) = 0.74, 95% confidence interval (CI) = 0.64-0.85]. This association was stronger in a subgroup of 1552 longevous participants (age between 90 and 111 years, adjusted HR = 0.72, 95% CI = 0.60-0.87). High genetic risk was associated with a 35% increased risk of frailty (adjusted HR = 1.35, 95% CI = 1.16-1.58). Of the participants with high genetic risk and no persistent aerobic exercises, there was a 59% increased risk of frailty (adjusted HR = 1.59, 95% CI = 1.20-2.09). HRs for the risk of frailty increased from the low genetic risk with persistent aerobic exercise to high genetic risk without persistent aerobic exercise (P trend <0.001). CONCLUSIONS: Both aerobic exercises and NMJ pathway-related genetic risk were significantly associated with frailty. Persistent aerobic exercises can partly offset NMJ pathway-related genetic risk to frailty in elderly people.

9.
ACS Sens ; 6(1): 245-251, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33373189

RESUMO

Four hydrogen bond-based macrocyclic and tripodal neutral receptors with increasing conformational complementarity with sulfate were used for the first time as ionophores to develop polymeric membrane sulfate-selective electrodes. Optimizing the membrane composition such as ionophores, lipophilic additives, and plasticizers yielded ISEs which showed Nernstian response to sulfate with the best selectivity so far and improved detection limits (a slope of -29.8 mV/dec in the linear range of 1 × 10-6-1 × 10-1 M with a detection limit of 5 × 10-7 M), which led to the success of the determination of sulfate in drinking water samples and neomycine tablets. The anion-ionophore complex constants in the membrane phase were determined and correlated with the selectivity sequence of the ISEs. Studies on the influence of pH of the sample solution demonstrated that the developed ISEs can be operated in a wide pH range of 3-8 with fast response and rapid (in 1 min) and long lifetime. The success of these ionophores represents a feasible strategy for overcoming the "Hofmeister series" by employing a combination of complementarity and hydrogen bonds.


Assuntos
Sulfatos , Eletrodos , Ligação de Hidrogênio , Ionóforos , Potenciometria
10.
Aging (Albany NY) ; 12(24): 26248-26262, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232272

RESUMO

Aging is an important factor affecting the deterioration of patients with coronavirus disease 2019 (COVID-19). The aging and degeneration of various tissues and organs in the elderly lead to impaired organ function. Underlying conditions such as chronic lung disease, cardiovascular disease, and diabetes in aged patients are associated with higher mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily interacts with the cell surface receptor angiotensin-converting enzyme (ACE) 2 and other accessory proteins such as 78 kDa glucose-regulated protein 78 (GRP78) and CD147. Thus, altered receptor signals in aging and chronic disease play a role in SARS-CoV-2 infection, and are associated with a higher risk of deterioration in different organs. In this review, after a brief introduction to the link between aging and receptors for SARS-CoV-2, we focus on the risk of deterioration in different organs of COVID-19 patients considering aging as the main factor. We further discuss the structural and/or physiological changes in the immune system and organs (lung, heart, kidney, vessels, nerve system), as well as those associated with diabetes, in aging patients, and speculate on the most likely mechanisms underlying the deterioration of COVID-19 patients.


Assuntos
COVID-19/epidemiologia , SARS-CoV-2 , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Enzima de Conversão de Angiotensina 2/metabolismo , Biomarcadores , COVID-19/metabolismo , COVID-19/virologia , Criança , Pré-Escolar , Comorbidade , Suscetibilidade a Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados da Assistência ao Paciente , Vigilância da População , Receptores Virais/metabolismo , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-33026978

RESUMO

Amphipathic helix (AH) features the segregation of polar and nonpolar residues and plays important roles in many membrane-associated biological processes through interacting with both the lipid and the soluble phases. Although the AH structure has been discovered for a long time, few ab initio machine learning-based prediction models have been reported, due to the limited amount of training data. In this study, we report a new deep learning-based prediction model, which is composed of a residual neural network and the uneven-thresholds decision algorithm. It is constructed on 121 membrane proteins, in total 51640 residue samples, which are curated from an up-to-date membrane protein structure database. Through a rigid 10-fold nested cross-validation experiment, we demonstrate that our model has exceeded the state-of-the-art approaches in this field. This presents a new avenue for accurately predicting AHs. Analysis on the contribution of the input residues and some cases further reveals the high interpretability and the generalization of our model.

12.
ACS Sens ; 5(11): 3465-3473, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33112603

RESUMO

Four Lewis acidic organo-antimony(V) compounds with strong binding affinity to fluoride were used for the first time as ionophores to fabricate polymeric membrane fluoride-selective electrodes. Improved detection limits and significant anti-Hofmeister selectivity could be achieved by optimizing ionophores, lipophilic additives, and plasticizers. Membrane electrodes fabricated with tetrakis-(pentafluorophenyl)stibonium (ionophore 2) performed best in detection limit, sensitivity, and selectivity. Optimal performance was obtained by fluoride with a slope of -59.5 mV/decade in the linear range of 1 × 10-5 to 4 × 10-2 M and a detection limit of 5 × 10-6 M. Studies on the influence of sample solution pH demonstrate that the best pH for fluoride determination is pH 3.0. All of the electrodes studied respond rapidly (in 1 min) in different concentrations of fluoride solutions. The anion-ionophore complex constants in the membrane phase determined using the segmented sandwich membrane method correlate well with the solution-phase binding data and determined selectivity sequence of the ion-selective electrodes. The possibility of real life application of the optimized electrodes was assessed by determination of fluoride concentrations in tap water.


Assuntos
Fluoretos , Ácidos de Lewis , Antimônio , Ionóforos , Membranas Artificiais , Potenciometria
13.
Anal Chem ; 92(21): 14740-14746, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33064457

RESUMO

A handful of bis/tetra-phosphonate calix[4]pyrroles with recognition sites embedding in hydrophobic cavitands were evaluated for the first time as ionophores for polymeric membrane Ach+-selective electrodes. Highly selective potentiometric Ach+ could be achieved over its analogues, especially for Ch+, which differs only by an acetate tail from Ach+. The superior performance of the proposed ISEs might be ascribed to a dual-site binding mode, in which the trimethylammonium head and acetate tail were accommodated by the phosphonate group-bridged aryl walls and the bowl-shaped aromatic cavity, through cation-π/charge-dipole interaction and the convergent four N-H···O hydrogen bonds, respectively. To gain more insight into the performance of the proposed ISEs, the cation-ionophore complex constants in the membrane phase were determined, and the binding affinity trend correlates well with the selectivity pattern. These results suggest that conformational preorganization of the ionophores and complementary weak interactions do change the selectivity of the ionophores. Studies on the influence of the sample solution pH demonstrated that the developed ISEs can be employed in a wide pH range of 4.0-9.6 with a fast response (<60 s), good reversibility, and long lifetime. Optimizing the membrane components, such as ionophores, lipophilic additives, and plasticizers, yielded ISEs, showing Nernstian responses to Ach+ with improved linear ranges and detection limits (a slope of -59.5 mV/dec in the linear range of 1 × 10-6-1 × 10-2 M with a detection limit of 3 × 10-7 M), which led to the success of the determination of Ach+ in spiked urine and milk samples.


Assuntos
Acetilcolina/análise , Éteres Cíclicos/química , Ionóforos/química , Limite de Detecção , Organofosfonatos/química , Potenciometria/instrumentação , Pirróis/química , Resorcinóis/química , Acetilcolina/química , Eletrodos , Ligação de Hidrogênio , Membranas Artificiais
14.
iScience ; 23(9): 101458, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32861994

RESUMO

The emerging immune checkpoint blockade (ICB) therapy has ushered the cancer therapeutics field into an era of immunotherapy. Although ICB treatment provides remarkable clinical responses in a subset of patients with cancer, this regimen fails to extend survival in a large proportion of patients. Here, we found that a combined treatment of estrogen receptor beta (ERß) agonist and PD-1 antibody treatment improved therapeutic efficacy in mouse tumor models, compared with monotherapies, by reducing infiltration of myeloid-derived suppressor cells (MDSCs) and increasing CD8+ T cells in tumors. Mechanistically, LY500307 treatment reduced tumor-derived CSF1 and decreased infiltration of CSF1R+ MDSCs in the tumor bed. CSF1 released by tumor cells induced CSF1R+ MDSC chemotaxis in vitro and blockade of CSF1R demonstrated similar therapeutic effects as ERß activation in vivo. Collectively, our study proved combined treatment of ERß agonist and PD-1 antibody reduced MDSC infiltration in the tumor and enhanced tumor response to ICB therapy.

15.
J Mol Neurosci ; 70(10): 1484-1492, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32602029

RESUMO

Alternative splicing (AS) is a ubiquitous mechanism in which pre-mRNA can be spliced into divergent variants and involved in carcinogenesis and progression in several cancers. In the present study, we systematically profiled prognostic AS signatures involving both low grade glioma (LGG) and glioblastoma (GBM) and investigated the association of AS signatures with tumor grade and IDH1 status in glioma. Percent spliced in (PSI) values and corresponding clinical data were obtained from TCGA SpliceSeq and TCGA data portal, respectively. Prognostic AS signatures were identified using univariate and stepwise multivariate Cox regression. Heatmap analysis was performed based on prognostic AS signatures. A prognostic signature was established with 69 and 88 AS events, including specific splicing events of MUTYH, STEAP3, and CTNNB1, in LGG and GBM cohorts, respectively. The area under the curve (AUC) of the prediction model was 0.968 at 2000 days of overall survival (OS) in the LGG cohort and 0.966 at 450 days of OS in the GBM cohort. In addition, these prognostic AS signatures could complement current molecular classification, such as IDH1 mutation, 1p/19q codeletion, and ATRX loss, of glioma and further identify potential subgroups of glioma with the same molecular features. In conclusion, our study systematically profiled prognostic AS events involving both low grade glioma and glioblastoma for the first time, which also shed light on the crosstalk between AS signatures and molecular features of glioma.

16.
Aging (Albany NY) ; 12(11): 10687-10703, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532929

RESUMO

INTRODUCTION: To investigate the independent and joint effects of leisure activities on disability in activities of daily living (ADL) among the oldest-old Chinese population (aged ≥ 80 years). RESULTS: A total of 3696 participants with ADL disability were identified during the median follow-up period of 3.1 years. Compared to the participants who "never" watched TV or listened to the radio and who "never" kept domestic animals or pets, those who engaged in these activities "almost every day" had a significantly lower ADL disability risk (adjusted hazard ratios were 0.74 and 0.66, respectively; both P < 0.001). Furthermore, participants engaging in multiple leisure activities showed a reduced risk of ADL disability (P for trend < 0.001). CONCLUSIONS: Frequently watching TV or listening to the radio and keeping domestic animals or pets was associated with a lower risk of ADL disability among the oldest-old Chinese population. METHODS: We included 12,331 participants (aged ≥ 80 years) (mean [SD] age: 89.5 [7.0] years) who managed to perform ADL independently at baseline in the Chinese Longitudinal Healthy Longevity Survey 1998-2014 waves. Cox proportional hazards models were used to examine whether leisure activities were associated with ADL disability.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência/estatística & dados numéricos , Atividades de Lazer , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Feminino , Inquéritos Epidemiológicos , Envelhecimento Saudável , Humanos , Estudos Longitudinais , Masculino , Modelos de Riscos Proporcionais , Fatores de Risco
17.
Ann Rheum Dis ; 79(6): 829-836, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253185

RESUMO

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças do Sistema Digestório/mortalidade , Glucosamina/uso terapêutico , Neoplasias/mortalidade , Doenças Respiratórias/mortalidade , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reino Unido/epidemiologia
18.
BMJ ; 368: m456, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131999

RESUMO

OBJECTIVES: To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort. DESIGN: Population based, prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018. MAIN EXPOSURE: All participants answered questions on the habitual use of supplements, including fish oil. MAIN OUTCOME MEASURES: All cause mortality, CVD mortality, and CVD events. RESULTS: At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005). CONCLUSIONS: Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais/estatística & dados numéricos , Óleos de Peixe/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
19.
Oncol Lett ; 19(3): 2346-2354, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194734

RESUMO

Adamantinomatous craniopharyngioma (ACP) is a benign epithelial tumor of the sellar region. Whether primary human cell cultures can be used as a stable research model has yet to be determined. The characteristics of three cultured craniopharyngioma primary cell (CPC) lines were identified using immunofluorescence. The culture duration for each CPC line was 10, 20 and 30 days. Cell lines and paired parental tumor tissues were subsequently analyzed using transcriptome sequencing (RNA-Seq). Transcriptomic differences between ACP tissues and CPC lines were compared. CPCs maintained the original epithelial lineage markers, including pan-cytokeratin and epithelial cell adhesion molecule. However, the Pearson's correlation coefficient of transcriptomes between each pair of CPC lines and ACP tissues decreased from 0.657 (cultured for 10 days) to 0.61 (cultured for 20 days) and further to 0.547 (cultured for 30 days). The number of differentially expressed genes between ACP tissues and CPCs was increased from 1,247 (cultured for 10 days) to 1,643 (cultured for 20 days) and then to 1,949 (cultured for 30 days). The results of Gene Set Enrichment Analysis demonstrated that the diversity of gene sets increased with longer culture time. Significant differences in the majority of signature gene sets were not observed between ACP tissues and CPCs, with the exception of keratinization phenotype [normalized enrichment score (NES)=-2.02, false discovery rate (FDR)=0.0038] and epithelial cell phenotype (NES=-1.82, FDR=0.032). Cell proliferation (NES=1.78, FDR=0.028) and mitosis (NES=1.93, FDR=0.012) were enhanced in CPCs. Therefore, primary human cell cultures can be used as a suitable research platform for ACP, however further experiments are required.

20.
J Gerontol A Biol Sci Med Sci ; 75(6): 1214-1221, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31435643

RESUMO

BACKGROUND: The aim of this study was to examine the trends in impairment regarding activities of daily living (ADL), physical performance, and cognitive function among the oldest-old (those aged 80 and older) in China between 1998 and 2014. METHODS: We used data on 34,297 oldest-old individuals from the seven waves of the Chinese Longitudinal Healthy Longevity Study. We estimated age, period, and cohort effects on the prevalence of self-reported ADL impairment, tested physical performance and cognitive function impairment using the age-period-cohort model. RESULTS: Regarding age, the prevalence of ADL, physical performance, and cognitive function impairment were highest in the centenarians, but they did not increase with age in this population. Among the literate subgroup, the prevalence of cognitive impairment increased more rapidly with age than that in the illiterate subgroup. Regarding period, the prevalence of self-reported and tested physical impairment slowly increased between 1998 and 2014, but cognitive impairment remained stable. Regarding cohort, ADL impairment continuously decreased. However, physical and cognitive impairment remained stable after a brief decline in the early birth cohorts. CONCLUSIONS: The results suggest that the age effect is still the most obvious effect regarding several types of functional impairment. The likelihood of a younger person experiencing functional impairment may not change significantly, but ADL is likely to be amenable to improvement resulting from improved medical and social care. Therefore, increased care for the oldest-old may considerably improve their quality of life, particularly regarding their basic ADL.


Assuntos
Atividades Cotidianas , Idoso de 80 Anos ou mais/estatística & dados numéricos , Disfunção Cognitiva/epidemiologia , Aptidão Física , Atividades Cotidianas/psicologia , Fatores Etários , Idoso de 80 Anos ou mais/fisiologia , Idoso de 80 Anos ou mais/psicologia , China/epidemiologia , Disfunção Cognitiva/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes de Estado Mental e Demência , Aptidão Física/psicologia , Fatores de Risco
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