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1.
J Sport Health Sci ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285309

RESUMO

OBJECTIVE: This study sought to analyze the prospective association between vigorous-intensity physical activity (VPA) and health-related outcomes in children and adolescents. METHODS: Studies reporting associations between device-measured VPA and health-related factors in children and adolescents aged 3-18 years were identified through database searches (MEDLINE, EMBASE, and SPORTDiscus). Correlation coefficients were pooled if outcomes were reported by at least 3 studies, using DerSimonian-Laird random effects models. RESULTS: Data from 23 studies including 12,056 participants were pooled using random effects models. Significant associations were found between VPA at baseline and overall adiposity (r = 0.09, 95% confidence interval (CI): -0.15 to -0.03, p = 0.002; I2 = 90.4%), cardiometabolic risk score (r = -0.13, 95%CI: -0.24 to -0.02, p = 0.020; I2 = 69.6%), cardiorespiratory fitness (r = 0.20, 95%CI: 0.13-0.28, p < 0.001; I2 = 0%), and total bone mineral density (r = 0.16, 95%CI: 0.06 to 0.25, p = 0.001; I2 = 0%). CONCLUSION: VPA seems to be negatively related to adiposity and cardiometabolic risk score and positively related to cardiorespiratory fitness and total body BMD among children and adolescents at follow-up. Therefore, our findings support the need to strengthen physical activity recommendations regarding VPA due its health benefits in children and adolescents.

2.
Br J Nutr ; : 1-32, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33292901

RESUMO

The relationship between adherence to the Mediterranean Diet (MD), physical activity (PA), sedentary behaviour and physical fitness levels has been analysed in several studies; however, there is mixed evidence among youth. Thus, this study aimed to meta-analyse the associations between adherence to the MD and PA, sedentary behaviour, and physical fitness among children and adolescents. Three databases were systematically searched, including cross-sectional and prospective designs with a sample of healthy youth aged 3-18 years. Random-effects inverse-variance model with the Hartung-Knapp-Sidik-Jonkman variance estimator based on DerSimonian-Laird were used to estimate the pooled effect size (correlation coefficient [r]). Thirty-nine studies were included in the meta-analysis, yielding a total of 565,421 youth (mean age, 12.4 years). Overall, the MD had a weak-to-moderate positive relationship with PA (r = 0.14; 95% confidence interval [CI], 0.11 to 0.17), cardiorespiratory fitness (r = 0.22; 95% CI, 0.13 to 0.31) and muscular fitness (r = 0.11; 95% CI, 0.03 to 0.18), and a small-to-moderate negative relationship with sedentary behaviour (r = -0.15; 95% CI, -0.20 to -0.10) and speed-agility (r = -0.06; 95% CI, -0.12 to -0.01). There was a high level of heterogeneity in all of the models (I2 ≥ 75%). Overall results did not remain significant after controlling for sex and age (children or adolescents) except for PA. Improving dietary habits toward those of the MD could be associated with higher physical fitness and PA in youth, lower sedentary behaviours and better health in general.

3.
J Alzheimers Dis ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33325386

RESUMO

To deeply understand late onset Alzheimer's disease (LOAD), it may be necessary to change the concept that it is a disease exclusively driven by aging processes. The onset of LOAD could be associated with a previous peripheral stress at the level of the gut (changes in the gut microbiota), obesity (metabolic stress), and infections, among other systemic/environmental stressors. The onset of LOAD, then, may result from the generation of mild peripheral inflammatory processes involving cytokine production associated with peripheral stressors that in a second step enter the brain and spread out the process causing a neuroinflammatory brain disease. This hypothesis could explain the potential efficacy of Sodium Oligomannate (GV-971), a mixture of acidic linear oligosaccharides that have shown to remodel gut microbiota and slowdown LOAD. However, regardless of the origin of the disease, the end goal of LOAD-related preventative or disease modifying therapies is to preserve dendritic spines and synaptic plasticity that underlay and support healthy cognition. Here we discuss how systemic/environmental stressors impact pathways associated with the regulation of spine morphogenesis and synaptic maintenance, including insulin receptor and the brain derived neurotrophic factor signaling. Spine structure remodeling is a plausible mechanism to maintain synapses and provide cognitive resilience in LOAD patients. Importantly, we also propose a combination of drugs targeting such stressors that may be able to modify the course of LOAD by acting on preventing dendritic spines and synapsis loss.

4.
Hepatology ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32893372

RESUMO

BACKGROUND & AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here we investigate the causal effects of risk factors considered in current GBC prevention programmes as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH & RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (p = 9 × 10-5 ) and Europeans (p = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (p = 0.03), while higher CRP concentrations increased GBC risk in Europeans (p = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (p = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean programme for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

5.
Children (Basel) ; 7(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967205

RESUMO

The aim of this study was to determine the minimum change in cardiorespiratory fitness (CRF) required to reduce adiposity (percent body fat) in exercise programs for overweight and obese youth. Studies were identified through a systematic search of five databases. Studies were limited to randomized controlled trials (RCTs) of exercise training (e.g., aerobic, strength, concurrent) that assessed percent body fat and CRF for both exercise and control groups in overweight and obese children and adolescents. A series of meta-regressions were conducted to explore links between change in CRF (maximum oxygen consumption, ml/kg/min) and change in percent body fat. Twenty-three RCTs were included (n = 1790, 59% females). Meta-regression analysis suggested that increases of at least 0.38 mL/kg/min in CRF (p < 0.001) were considered to be a clinically important reduction of percent body fat (-2.30%, 95% confidence interval -3.02 to -1.58; p < 0.001; I2 = 92.2%). Subgroup analysis showed that increases of at least 0.17 mL/kg/min in CRF favored a reduction of percent body fat of -1.62% (95% confidence interval -2.04 to -1.20; p < 0.001; I2 = 69.9%). In conclusion, this change in CRF could be considered by pediatric researchers, youth fitness specialists, and health care providers to determine the effectiveness in body fat reductions through exercise.

6.
Arch Bronconeumol ; 2020 Sep 15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32948369

RESUMO

INTRODUCTION: While the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry. METHODS: COPD patients (n=214) and age-matched controls (n=193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers. RESULTS: CODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p=0.04, OR=2.07). HLA-DRB1*01:02 was also significantly associated with FEV1 (p=0.04) and oxygen saturation (p=0.02), and the FEV1/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p=9×10-3). CONCLUSION: We report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.

7.
Environ Health ; 19(1): 89, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843052

RESUMO

BACKGROUND: Household air pollution (HAP) is a significant source of the global burden of disease. Our objective was to evaluate the association between environmental health literacy (EHL), a domain of health literacy (HL) that describes the ability to use environmental health information to reduce health risks, and symptoms associated with HAP. METHODS: We performed a cross-sectional population-based study of 353 households in Kasarani, Kenya. One individual from each household was surveyed using our novel EHL survey tool. Baseline characteristics were compared between individuals who were symptomatic (i.e., experiencing cough, shortness of breath, phlegm production, wheeze, chest tightness, headache, eye irritation, or burns from cooking at least 5 times per month) versus individuals who were asymptomatic (i.e., experiencing none or symptoms no more than once per month). Multivariate logistic regression was used to determine the odds ratios (OR) of self-reported symptoms associated with HL, stratified by median EHL, adjusting for education, self-perceived health and solid fuel use. RESULTS: A total of 100 individuals (28%) reported experiencing one or more symptoms at least 5 times per month, including 31.2% of solid fuel users and 30.3% of non-solid fuel users. Among individuals with high EHL, higher HL was associated with lower risk of experiencing symptoms (OR = 0.26; 95% CI 0.10-0.67), however, there was no association among individuals with low EHL (OR = 0.85; 95% CI 0.34-2.13). Among solid fuel users, the association between HL and risk of experiencing symptoms was driven by individuals with high EHL (OR = 0.30; 95% CI 0.05-1.84), rather than those with low EHL (OR = 1.22; 95% CI 0.36-4.16). CONCLUSIONS: To the best of our knowledge, this was the first study to assess the association between EHL, HL, and HAP-associated symptoms. Our findings highlight the potential importance of EHL in promoting sustainable interventions to reduce symptoms associated with HAP from solid fuel use among communities in Kenya.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental/análise , Saúde Ambiental/estatística & dados numéricos , Letramento em Saúde/estatística & dados numéricos , Estudos Transversais , Humanos , Quênia , População Urbana
8.
J Pers Med ; 10(3)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824824

RESUMO

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5×10-4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10-3 to 3.77×10-8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.

9.
Eur J Clin Invest ; 50(10): e13382, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32780415

RESUMO

In barely nine months, the pandemic known as COVID-19 has spread over 200 countries, affecting more than 22 million people and causing over than 786 000 deaths. Elderly people and patients with previous comorbidities such as hypertension and diabetes are at an increased risk to suffer a poor prognosis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although the same could be expected from patients with chronic obstructive pulmonary disease (COPD), current epidemiological data are conflicting. This could lead to a reduction of precautionary measures in these patients, in the context of a particularly complex global health crisis. Most COPD patients have a long history of smoking or exposure to other harmful particles or gases, capable of impairing pulmonary defences even years after the absence of exposure. Moreover, COPD is characterized by an ongoing immune dysfunction, which affects both pulmonary and systemic cellular and molecular inflammatory mediators. Consequently, increased susceptibility to viral respiratory infections have been reported in COPD, often worsened by bacterial co-infections and leading to serious clinical outcomes. The present paper is an up-to-date review that discusses the available research regarding the implications of coronavirus infection in COPD. Although validation in large studies is still needed, COPD likely increases SARS-CoV-2 susceptibility and increases COVID-19 severity. Hence, specific mechanisms to monitor and assess COPD patients should be addressed in the current pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Betacoronavirus , Biomassa , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Suscetibilidade a Doenças , Exposição Ambiental/estatística & dados numéricos , Predisposição Genética para Doença , Humanos , Pandemias , Material Particulado , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Índice de Gravidade de Doença , Fumaça , Fumar/epidemiologia , Fumar/imunologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-32781539

RESUMO

BACKGROUND: Self-regulation comprises a series of important competencies, such as the ability to control inner states or responses toward thoughts, attention, emotions, or even performance. The relationship between self-regulation and different healthy lifestyle behaviors among children has not been examined in depth to date. The aim of this study was to explore the association between physical activity, screen time levels, and/or Mediterranean Diet adherence and self-regulation in Chilean children. METHODS: A total of 1561 children aged 8-12 years from eight public schools with low socioeconomic status were included. Physical activity, screen time, Mediterranean Diet, and self-regulation were assessed with validated questionnaires. RESULTS: Children who were classified as active or those who reported less than 2 h per day of screen time had higher self-regulation than those who were classified as inactive or counterparts with 2 h per day or more of screen time, respectively. Using joint categories, active children both with low and high screen time showed higher self-regulation compared to inactive/high screen time peers. Additionally, active groups with adherence or non-adherence to the Mediterranean Diet had higher self-regulation compared to inactive and non-adherence peers. CONCLUSION: Having a greater number of healthy habits, mainly regular physical activity, was associated with higher self-regulation, which might be one potential strategy to promote child social-emotional development.


Assuntos
Dieta Mediterrânea , Estilo de Vida Saudável , Autocontrole , Criança , Chile , Estudos Transversais , Dieta , Exercício Físico , Feminino , Humanos , Estilo de Vida , Masculino , Qualidade de Vida , Comportamento Sedentário , Inquéritos e Questionários
11.
Cells ; 9(8)2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823764

RESUMO

The c-Jun N-terminal Kinases (JNKs) are a group of regulatory elements responsible for the control of a wide array of functions within the cell. In the central nervous system (CNS), JNKs are involved in neuronal polarization, starting from the cell division of neural stem cells and ending with their final positioning when migrating and maturing. This review will focus mostly on isoform JNK1, the foremost contributor of total JNK activity in the CNS. Throughout the text, research from multiple groups will be summarized and discussed in order to describe the involvement of the JNKs in the different steps of neuronal polarization. The data presented support the idea that isoform JNK1 is highly relevant to the regulation of many of the processes that occur in neuronal development in the CNS.

12.
Expert Opin Drug Discov ; 15(9): 993-1004, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32450711

RESUMO

INTRODUCTION: Opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson's disease (PD) associated with L-DOPA/L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Thus, OPC decreases fluctuation in L-DOPA plasma levels and favors more constant central dopaminergic receptor stimulation, thus improving PD symptomatology. AREAS COVERED: This review evaluates the preclinical development, pharmacology, pharmacokinetics and safety profile of OPC. Data was extracted from published preclinical and clinical studies published on PUBMED and SCOPUS (Search period: 2000-2019). Clinical and post-marketing data are also evaluated. EXPERT OPINION: OPC is a third generation COMT inhibitor with a novel structure. It has an efficacy and tolerability superior to its predecessors, tolcapone (TOL) and entacapone (ENT). It also provides a safe and simplified drug regimen that allows neurologists to individually adjust the existing daily administration of L-DOPA. OPC is indicated as an adjunctive therapy to L-DOPA/DDI in patients with PD and end-of-dose motor fluctuations who cannot be stabilized on those combinations.

13.
Respiration ; 99(4): 307-315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32222710

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with ∼1% of Latin American ancestry. OBJECTIVE: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. METHOD: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p ≤ 0.001), call rates (<95%), and minor allele frequencies (<0.5%) in controls, 455,564 markers were available for logistic regression. RESULTS: PRDM15 rs1054761 C allele (p = 2.22 × 10-7) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10-6). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. CONCLUSION: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.

14.
Cancer Epidemiol ; 65: 101643, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32058310

RESUMO

BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Neoplasias da Vesícula Biliar/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Chile/epidemiologia , Europa (Continente)/epidemiologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Estudos de Associação Genética , Humanos , Índios Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
15.
Curr Pharm Des ; 26(12): 1251-1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31931694

RESUMO

The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, Huntington's disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.


Assuntos
Doença de Alzheimer , Ácido Glutâmico , Humanos , Memantina/farmacologia , Neurônios/fisiologia
17.
Mol Neurobiol ; 57(4): 1814-1827, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31838720

RESUMO

Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been previously investigated for its neuroprotective effects in vitro and in vivo. In the present study, we aimed to evaluate its possible beneficial effects in a well-established preclinical mixed model of familial Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) based on the use of transgenic APPswe/PS1dE9 (APP/PS1) mice fed with a high fat diet (HFD). C57BL/6 wild-type (WT) and APP/PS1 mice were used in this study. APP/PS1 mice were fed with a palmitic acid-enriched HFD (APP/PS1 HFD) containing 45% of fat mainly from hydrogenated coconut oil. Intraperitoneal glucose tolerance tests (IP-GTT) and insulin tolerance tests (IP-ITT) were performed. Western blot analyses were performed to analyse protein expression, and water maze and novel object recognition test were done to evaluate the cognitive process. EGCG treatment improves peripheral parameters such as insulin sensitivity or liver insulin pathway signalling, as well as central memory deficits. It also markedly increased synaptic markers and cAMP response element binding (CREB) phosphorylation rates, as a consequence of a decrease in the unfolded protein response (UPR) activation through the reduction in the activation factor 4 (ATF4) levels and posterior downregulation of protein tyrosine phosphatase 1B (PTP1B). Moreover, EGCG significantly decreased brain amyloid ß (Aß) production and plaque burden by increasing the levels of α-secretase (ADAM10). Also, it led to a reduction in neuroinflammation, as suggested by the decrease in astrocyte reactivity and toll-like receptor 4 (TLR4) levels. Collectively, evidence suggests that chronic EGCG prevents distinct neuropathological AD-related hallmarks. This study also provides novel insights into the metabolic and neurobiological mechanisms of EGCG against cognitive loss through its effects on UPR function, suggesting that this compound may be a promising disease-modifying treatment for neurodegenerative diseases.

18.
J Mol Med (Berl) ; 97(12): 1723-1733, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31797011

RESUMO

The development of metabolic alterations like insulin resistance has been associated with dysfunctions in mitochondrial oxidative capacity, induction of neuroinflammatory responses, and the appearance of cognitive impairments in the brain. The c-Jun N-terminal Kinase 1 (JNK1) is a potential key modulator of these mechanisms. The current study identifies a protective effect of whole-body JNK1 knockout in the presence of a high-fat diet (HFD). Specifically, the data suggest that mice missing JNK1 show increased insulin sensitivity and mitochondrial activity, as well as reduced body weight, and astrocyte and microglial reactivity. Finally, these animals are also protected against HFD-induced cognitive impairments as assessed through novel object recognition test, the observation of dendritic spines, and the levels of BDNF or other proteins like spinophilin and ARC. Thus, modulation of JNK1 activity seems like a promising approach for the design of therapies aimed at treating metabolic-induced cognitive impairments. KEY MESSAGES: JNK1 is a link between obesity/type 2 diabetes and cognitive loss Inhibition of JNK1 is neuroprotective JNK1 constitutes a therapeutic strategy for cognitive loss.


Assuntos
Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 2/complicações , Hipocampo/metabolismo , Mitocôndrias/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Animais , Astrócitos/metabolismo , Peso Corporal/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Espinhas Dendríticas/genética , Espinhas Dendríticas/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/genética , Masculino , Testes de Memória e Aprendizagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Mitocôndrias/enzimologia , Mitocôndrias/genética , Proteína Quinase 8 Ativada por Mitógeno/genética , Proteínas do Tecido Nervoso/metabolismo
19.
Front Aging Neurosci ; 11: 236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551756

RESUMO

Nowadays, Alzheimer's disease (AD) is a severe sociological and clinical problem. Since it was first described, there has been a constant increase in its incidence and, for now, there are no effective treatments since current approved medications have only shown short-term symptomatic benefits. Therefore, it is imperative to increase efforts in the search for molecules and non-pharmacological strategies that are capable of slowing or stopping the progress of the disease and, ideally, to reverse it. The amyloid cascade hypothesis based on the fundamental role of amyloid has been the central hypothesis in the last 30 years. However, since amyloid-directed treatments have shown no relevant beneficial results other theories have been postulated to explain the origin of the pathology. The brain is a highly metabolically active energy-consuming tissue in the human body. It has an almost complete dependence on the metabolism of glucose and uses most of its energy for synaptic transmission. Thus, alterations on the utilization or availability of glucose may be cause for the appearance of neurodegenerative pathologies like AD. In this review article, the hypothesis known as Type 3 Diabetes (T3D) will be evaluated by summarizing some of the data that has been reported in recent years. According to published research, the adherence over time to low saturated fatty acids diets in the context of the Mediterranean diet would reduce the inflammatory levels in brain, with a decrease in the pro-inflammatory glial activation and mitochondrial oxidative stress. In this situation, the insulin receptor pathway would be able to fine tune the mitochondrial biogenesis in neuronal cells, regulation the adenosine triphosphate/adenosine diphosphate intracellular balance, and becoming a key factor involved in the preservation of the synaptic connexions and neuronal plasticity. In addition, new targets and strategies for the treatment of AD will be considered in this review for their potential as new pharmacological or non-pharmacological approaches.

20.
J. pediatr. (Rio J.) ; 95(4): 435-442, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040341

RESUMO

Abstract Objective: The aim of this study was to investigate the relation between health-related physical fitness and weight status in 13- to 15-year-old Latino adolescents. Method: The final sample consisted of 73,561 adolescents aged 13 -15 years (35,175 girls) from Chile (n = 48,771) and Colombia (n = 24,790). Cardiorespiratory and musculoskeletal fitness were measured using 20-m shuttle run (relative peak oxygen uptake - VO2peak) and standing broad jump test (lower body explosive strength), respectively. The International Obesity Task Force definition was used to define weight status (i.e., underweight, normal weight, overweight, and obese). Results: The present study found an inverted J-shape relationship between body mass index, cardiorespiratory fitness, and musculoskeletal fitness in both genders and all age groups (p < 0.01). Results also suggest that underweight adolescents, and not just overweight and obese adolescents, have lower odds of having a healthy cardiorespiratory fitness (based on new international criterion-referenced standards) profile when compared with their normal weight peers, except in girls aged 14 (p = 0.268) and 15 years (p = 0.280). Conclusions: The present results indicate low cardiorespiratory fitness and musculoskeletal fitness levels in underweight, overweight, and obese adolescents when compared with their normal weight peers. The findings appear to suggest that exercise programs should to decrease fat mass in overweight/obese adolescents and increase muscle mass in underweight adolescents.


Resumo Objetivo: Investigar a relação entre a aptidão física relacionada à saúde e o status do peso em adolescentes latinos de 13 a 15 anos. Método: A amostra final consistiu em 73.561 adolescentes entre 13 e 15 anos (35.175 meninas) do Chile (n = 48.771) e da Colômbia (n = 24.790). As aptidões cardiorrespiratória e musculoesquelética foram medidas com a corrida vaivém de 20 m (consumo máximo de oxigênio relativo - VO2máx.) e o teste de impulso horizontal (menor força explosiva do corpo), respectivamente. A definição Força-Tarefa Internacional de Obesidade foi usada para definir o status do peso (ou seja, abaixo do peso, peso normal, sobrepeso e obeso). Resultados: O presente estudo encontrou uma relação na forma de J invertido entre o índice de massa corporal, a aptidão cardiorrespiratória e a aptidão musculoesquelética em ambos os sexos e em todas as faixas etárias (p < 0,01). Os resultados também sugerem que os adolescentes abaixo do peso e não somente os adolescentes acima do peso e obesos têm menor chance de ter um perfil de aptidão cardiorrespiratória saudável (com base em novos padrões internacionais referenciados a critério) em comparação com os pares com peso normal, exceto em meninas de 14 (p = 0,268) e 15 anos (p = 0,280). Conclusões: Nossos resultados mostram baixos níveis de aptidão cardiorrespiratória e aptidão musculoesquelética em adolescentes abaixo do peso, acima do peso e obesos em comparação com os pares com peso normal. Os achados parecem sugerir que os programas de exercícios devam ser voltados para reduzir a massa gorda em adolescentes com sobrepeso/obesos e aumentar a massa muscular em adolescentes abaixo do peso.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Magreza/epidemiologia , Sobrepeso/epidemiologia , Aptidão Cardiorrespiratória/fisiologia , Obesidade/epidemiologia , Fatores Socioeconômicos , Peso Corporal , Índice de Massa Corporal , Chile/epidemiologia , Fatores Sexuais , Estudos Transversais , Colômbia/epidemiologia , Teste de Esforço , Força Muscular/fisiologia
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