Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 226
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 187(8): 1971-1989.e16, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38521060

RESUMO

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types.


Assuntos
Esclerose Lateral Amiotrófica , Degeneração Lobar Frontotemporal , Córtex Pré-Frontal , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Demência Frontotemporal/genética , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Perfilação da Expressão Gênica , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Análise da Expressão Gênica de Célula Única
2.
Annu Rev Biochem ; 84: 765-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26034893

RESUMO

Hydrogen peroxide (H2O2) is a prime member of the reactive oxygen species (ROS) family of molecules produced during normal cell function and in response to various stimuli, but if left unchecked, it can inflict oxidative damage on all types of biological macromolecules and lead to cell death. In this context, a major source of H2O2 for redox signaling purposes is the NADPH oxidase (Nox) family of enzymes, which were classically studied for their roles in phagocytic immune response but have now been found to exist in virtually all mammalian cell types in various isoforms with distinct tissue and subcellular localizations. Downstream of this tightly regulated ROS generation, site-specific, reversible covalent modification of proteins, particularly oxidation of cysteine thiols to sulfenic acids, represents a prominent posttranslational modification akin to phosphorylation as an emerging molecular mechanism for transforming an oxidant signal into a dynamic biological response. We review two complementary types of chemical tools that enable (a) specific detection of H2O2 generated at its sources and (b) mapping of sulfenic acid posttranslational modification targets that mediate its signaling functions, which can be used to study this important chemical signal in biological systems.


Assuntos
Peróxido de Hidrogênio/metabolismo , NADPH Oxidases/metabolismo , Transdução de Sinais , Animais , Humanos , Oxirredução , Ácidos Sulfênicos/metabolismo
3.
Nature ; 603(7903): 893-899, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35158371

RESUMO

Despite the importance of the cerebrovasculature in maintaining normal brain physiology and in understanding neurodegeneration and drug delivery to the central nervous system1, human cerebrovascular cells remain poorly characterized owing to their sparsity and dispersion. Here we perform single-cell characterization of the human cerebrovasculature using both ex vivo fresh tissue experimental enrichment and post mortem in silico sorting of human cortical tissue samples. We capture 16,681 cerebrovascular nuclei across 11 subtypes, including endothelial cells, mural cells and three distinct subtypes of perivascular fibroblast along the vasculature. We uncover human-specific expression patterns along the arteriovenous axis and determine previously uncharacterized cell-type-specific markers. We use these human-specific signatures to study changes in 3,945 cerebrovascular cells from patients with Huntington's disease, which reveal activation of innate immune signalling in vascular and glial cell types and a concomitant reduction in the levels of proteins critical for maintenance of blood-brain barrier integrity. Finally, our study provides a comprehensive molecular atlas of the human cerebrovasculature to guide future biological and therapeutic studies.


Assuntos
Células Endoteliais , Doença de Huntington , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Células Endoteliais/metabolismo , Humanos , Doença de Huntington/metabolismo , Sistema Imunitário , Neuroglia , Proteínas/metabolismo
4.
Nucleic Acids Res ; 51(4): 1750-1765, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36744436

RESUMO

Many replicative DNA polymerases couple DNA replication and unwinding activities to perform strand displacement DNA synthesis, a critical ability for DNA metabolism. Strand displacement is tightly regulated by partner proteins, such as single-stranded DNA (ssDNA) binding proteins (SSBs) by a poorly understood mechanism. Here, we use single-molecule optical tweezers and biochemical assays to elucidate the molecular mechanism of strand displacement DNA synthesis by the human mitochondrial DNA polymerase, Polγ, and its modulation by cognate and noncognate SSBs. We show that Polγ exhibits a robust DNA unwinding mechanism, which entails lowering the energy barrier for unwinding of the first base pair of the DNA fork junction, by ∼55%. However, the polymerase cannot prevent the reannealing of the parental strands efficiently, which limits by ∼30-fold its strand displacement activity. We demonstrate that SSBs stimulate the Polγ strand displacement activity through several mechanisms. SSB binding energy to ssDNA additionally increases the destabilization energy at the DNA junction, by ∼25%. Furthermore, SSB interactions with the displaced ssDNA reduce the DNA fork reannealing pressure on Polγ, in turn promoting the productive polymerization state by ∼3-fold. These stimulatory effects are enhanced by species-specific functional interactions and have significant implications in the replication of the human mitochondrial DNA.


Assuntos
DNA Polimerase gama , Replicação do DNA , Proteínas de Ligação a DNA , Humanos , DNA Polimerase gama/metabolismo , DNA de Cadeia Simples , Proteínas de Ligação a DNA/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo
5.
Proc Natl Acad Sci U S A ; 119(35): e2205425119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35994651

RESUMO

Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an endoplasmic reticulum (ER)-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER-PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK, and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.


Assuntos
Proteínas de Transporte , Membrana Celular , Lipídeos , Proteínas de Transporte Vesicular , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/metabolismo , Humanos , Neuroacantocitose/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
6.
J Cell Mol Med ; 28(8): e18153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568071

RESUMO

The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Trombose , Doenças Vasculares , Humanos , Quinases Associadas a rho/genética , Células Endoteliais
7.
J Strength Cond Res ; 38(2): 266-273, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088901

RESUMO

ABSTRACT: Heredia-Elvar, JR, Juan-Recio, C, Prat-Luri, A, Barbado, D, Ríos-Calonge, Jdl, and Vera-Garcia, FJ. Exercise intensity progressions and criteria to prescribe core stability exercises in young physically active men: a smartphone accelerometer-based study. J Strength Cond Res 38(2): 266-273, 2024-The establishment of core stability (CS) exercise intensity progressions in sport and clinical settings is normally based on subjective criteria. Therefore, this study aimed to develop exercise intensity progressions for some of the most common CS exercises through smartphone accelerometry and to analyze the effect of the subjects' lumbopelvic postural control on these progressions. Fifty-seven healthy young physically active male students performed 7 isometric variations of front bridge, back bridge, side bridge, and bird-dog exercises with a smartphone accelerometer placed on the pelvis. Mean pelvic accelerations were calculated during each variation to evaluate the lumbopelvic postural control challenge imposed on the subjects as an index of exercise intensity of difficulty. For the bridge exercises, long bridging produced higher pelvic accelerations than short bridging, bridging with single-leg support was more intense than bridging with double-leg support (even with both legs on a hemisphere ball for the back and front bridge), and the most difficult variations were those performed on a Swiss ball, mainly the variations with single-leg support. For the bird-dog exercise, the 2-point positions were more intense than the 3-point positions, the variations performed with a knee on the hemisphere ball produced higher pelvic accelerations than similar variations performed with the forearm on the hemisphere ball, and the variations with limb motions generated higher pelvic accelerations than similar variations performed without limb motions. Although the CS exercise progressions were very similar across subjects, our results showed the need to individualize the prescription of the CS exercise progressions based on the subjects' lumbopelvic postural control level.


Assuntos
Estabilidade Central , Smartphone , Humanos , Masculino , Acelerometria , Eletromiografia , Terapia por Exercício , Extremidade Inferior
8.
Scand J Med Sci Sports ; 33(9): 1661-1676, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37322570

RESUMO

OBJECTIVE: This study aimed to assess the residual effects of a 12-week concurrent training program (power training + high-intensity interval training) in older adults with chronic obstructive pulmonary disease (COPD). METHODS: A total of 21 older adults with COPD [intervention (INT), n = 8; control (CON), n = 13; 76.9 ± 6.8 years] were assessed at baseline and 10 months after the completion of the intervention by the short physical performance battery (SPPB), health-related quality of life (EQ-5D-5L), vastus lateralis muscle thickness (MT), peak pulmonary oxygen uptake (peak VO2 ) and peak work rate (Wpeak ), early and late isometric rate of force development (RFD), leg and chest press maximum muscle power (LPmax and CPmax ), and systemic oxidative damage and antioxidant capacity. RESULTS: Compared to baseline, after 10 months of detraining, the INT group presented increased SPPB (∆ = 1.0 point), health-related quality of life (∆ = 0.07 points), early RFD (∆ = 834 N∙s-1 ), LPmax (∆ = 62.2 W), and CPmax (∆ = 16.0 W) (all p < 0.05). In addition, a positive effect was noted in INT compared to CON regarding MT and Wpeak (both p < 0.05). No between-group differences were reported in peak VO2 , late RFD, systemic oxidative damage, and antioxidant capacity from baseline to 10 months after the completion of the intervention (all p > 0.05). CONCLUSIONS: Twelve weeks of concurrent training were enough to ensure improved physical function, health-related quality of life, early RFD and maximum muscle power and to preserve MT and Wpeak but not peak VO2 , late RFD, systemic oxidative damage and antioxidant capacity in the subsequent 10 months of detraining in older adults with COPD.


Assuntos
Treinamento Intervalado de Alta Intensidade , Músculo Esquelético , Doença Pulmonar Obstrutiva Crônica , Treinamento Resistido , Músculo Esquelético/fisiopatologia , Estresse Oxidativo , Antioxidantes/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , Humanos , Idoso , Idoso de 80 Anos ou mais , Consumo de Oxigênio , Força Muscular , Desempenho Físico Funcional , Qualidade de Vida , Masculino , Feminino
9.
J Am Chem Soc ; 144(14): 6227-6236, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35364811

RESUMO

Tryptophan (Trp) plays a variety of critical functional roles in protein biochemistry; however, owing to its low natural frequency and poor nucleophilicity, the design of effective methods for both single protein bioconjugation at Trp as well as for in situ chemoproteomic profiling remains a challenge. Here, we report a method for covalent Trp modification that is suitable for both scenarios by invoking photo-induced electron transfer (PET) as a means of driving efficient reactivity. We have engineered biaryl N-carbamoyl pyridinium salts that possess a donor-acceptor relationship that enables optical triggering with visible light whilst simultaneously attenuating the probe's photo-oxidation potential in order to prevent photodegradation. This probe was assayed against a small bank of eight peptides and proteins, where it was found that micromolar concentrations of the probe and short irradiation times (10-60 min) with violet light enabled efficient reactivity toward surface exposed Trp residues. The carbamate transferring group can be used to transfer useful functional groups to proteins including affinity tags and click handles. DFT calculations and other mechanistic analyses reveal correlations between excited state lifetimes, relative fluorescence quantum yields, and chemical reactivity. Biotinylated and azide-functionalized pyridinium salts were used for Trp profiling in HEK293T lysates and in situ in HEK293T cells using 440 nm LED irradiation. Peptide-level enrichment from live cell labeling experiments identified 290 Trp modifications, with 82% selectivity for Trp modification over other π-amino acids, demonstrating the ability of this method to identify and quantify reactive Trp residues from live cells.


Assuntos
Proteoma , Triptofano , Elétrons , Células HEK293 , Humanos , Luz , Peptídeos/química , Sais , Triptofano/química
10.
New Phytol ; 235(6): 2406-2423, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35704043

RESUMO

The analysis of plant elemental composition and the underlying factors affecting its variation are a current hot topic in ecology. Ecological adaptation to atypical soils may shift plant elemental composition. However, no previous studies have evaluated its relevance against other factors such as phylogeny, climate or individual soil conditions. We evaluated the effect of the phylogeny, environment (climate, soil), and affinity to gypsum soils on the elemental composition of 83 taxa typical of Iberian gypsum ecosystems. We used a new statistical procedure (multiple phylogenetic variance decomposition, MPVD) to decompose total explained variance by different factors across all nodes in the phylogenetic tree of target species (covering 120 million years of Angiosperm evolution). Our results highlight the relevance of phylogeny on the elemental composition of plants both at early (with the development of key preadaptive traits) and recent divergence times (diversification of the Iberian gypsum flora concurrent with Iberian gypsum deposit accumulation). Despite the predominant phylogenetic effect, plant adaptation to gypsum soils had a strong impact on the elemental composition of plants, particularly on sulphur concentrations, while climate and soil effects were smaller. Accordingly, we detected a convergent evolution of gypsum specialists from different lineages on increased sulphur and magnesium foliar concentrations.


Assuntos
Sulfato de Cálcio , Ecossistema , Filogenia , Plantas/genética , Solo , Enxofre
11.
BMC Geriatr ; 22(1): 747, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36096728

RESUMO

OBJECTIVES: Frailty and sarcopenia have been related with adverse events, including hospitalization. However, its combined effect with hospitalization-related outcomes, including costs, has not been previously investigated. Our purpose was to explore how frailty, sarcopenia and its interaction could impact on healthcare expenditures. METHODS: 1358 community-dwelling older adults from the Toledo Study of Healthy Ageing (TSHA) were included. Sarcopenia was measured using the Foundation for the National Institutes of Health criteria fitted to our cohort. Frailty was defined according to Frailty Trait Scale 5 (FTS5) and the Frailty Index fitted to the cut-off points of TSHA population. Hospitalization costs were taken from hospital records and costs were attributed according to Diagnostic-Related Groups, using as the cost base year 2015. Two-part regression models were used to analyze the relationship between frailty and sarcopenia and hospital admission, number of hospitalizations, length of stay and hospitalization costs. RESULTS: Sarcopenia was associated only with the probability of being admitted to hospital. Frailty was also associated with higher hospital use, regardless of the frailty tool used, but in addition increased hospital admission costs at follow-up by 23.72% per year and by 19.73% in the full model compared with non-frail individuals. The presence of sarcopenia did not increase the costs of frailty but, by opposite, frailty significantly increased the costs in people with sarcopenia, reaching by 46-56%/patient/year at follow-up. Older adults with frailty and sarcopenia had a higher risk of hospitalization, disregarding the tool used to assess frailty, and higher hospitalization costs (FTS5) in the full model, at the cross-sectional and at the follow-up level. CONCLUSIONS: Frailty is associated with increased hospitalization costs and accounts for the potential effects of sarcopenia.


Assuntos
Fragilidade , Sarcopenia , Idoso , Estudos Transversais , Fragilidade/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/terapia , Estados Unidos
12.
Scand J Med Sci Sports ; 31(6): 1164-1182, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33533045

RESUMO

Investigations into the sensitivity of heart rate-(HR) derived indices for tracking parasympathetic nervous system (PNS) changes in functionally overreached (F-OR) endurance-trained athletes have produced equivocal findings. Lack of clarity may be a result of methodological inconsistencies. Therefore, the aims of this systematic review and meta-analysis were (a) to determine the sensitivity of resting and post-exercise vagal-related HR variability (HRV) and HR recovery (HRR) indices to detect PNS modulation in F-OR and non-overreached (non-OR) athletes, and (b) to investigate the influence of methodological factors on the sensitivity of HR-based indices to detect PNS hyperactivity in F-OR athletes. We searched CENTRAL, Scopus, PubMed, Embase, and Web of Science up to May 2020 for the following terms: male and female endurance-trained athletes, controlled and uncontrolled studies that carried out an overload training period, and PNS modulation measured in resting and post-exercise, pre- and post-overload training period. A random-effects model of standardized mean difference (SMD) was estimated for each outcome measure based on the training-induced fatigue status (F-OR vs non-OR athletes), and the influence of methodological issues to detect PNS hyperactivity in F-OR was assessed by subgroup analyses. Pooled analysis showed that resting vagal-related HRV indices did not detect PNS hyperactivity in F-OR athletes (SMD+ = -0.01; 95% confidence interval [CI] = -0.51, 0.50), and no statistical difference (P = .600) was found with non-OR athletes (SMD+ = 0.15; 95% CI = -0.14, 0.45). However, subgroup analysis based on HRV parameter showed a moderate statistical increase in weekly averaged HRV in F-OR athletes (SMD+ = 0.81; 95% CI = 0.35, 1.26), while isolated HRV values did not reach statistical significance (SMD+ = -0.45; 95% CI = -0.96, 0.06). We observed a moderate and statistically significant increase in HRR indices among F-OR athletes (SMD+ = 0.65; 95% CI = 0.44, 0.87), no changes for non-OR athletes (SMD+ = 0.10; 95% CI = -0.15, 0.34), and statistically significant differences between F-OR and non-OR athletes (P < .001). Insufficient data prevented meta-analysis for post-exercise vagal-related HRV indices. Our findings show that when methodological factors are considered, HR-based indices are sensitive to increased PNS modulation in F-OR.


Assuntos
Atletas , Frequência Cardíaca/fisiologia , Sistema Nervoso Parassimpático/fisiologia , Resistência Física/fisiologia , Descanso/fisiologia , Adulto , Desempenho Atlético/fisiologia , Intervalos de Confiança , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Condicionamento Físico Humano/fisiologia , Fatores de Tempo , Nervo Vago/fisiologia
13.
BMC Geriatr ; 21(1): 363, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126942

RESUMO

BACKGROUND: Older patients who spend long periods hospitalized or those who are in a situation of institutionalization represent a risk group in this regard, as many of them suffer a degree of dependence and need help to perform the basic tasks of personal care. It is therefore important to learn more of the oral health status of this group of patients in order to make a proper assessment of the situation and to develop protocols for its management. The purpose of the study was to conduct a systematic review to ascertain the oral health status of older people patients admitted to institutions or hospitalized for a long period of time. METHODS: a systematic review of the literature published in two different databases (PubMed, Embase and Cochrane Library) was carried out, with 12 different combinations of keywords based on the following selection criteria: studies published in the last 5 years, in English and/or Spanish and/or Portuguese, with samples of ≥30 patients, performed in patients older than 65 years, admitted to any type of institution and/or hospital center for at least 7 days and in which the state of hard and/or soft tissues of the oral cavity were evaluated in some way. The selected articles were subjected to a thorough analysis. RESULTS: The search strategy covered 1.014 articles: 689 from Pubmed and 325 from Cochrane Library. After applying the eligibility criteria, five articles were selected for our review. The level of evidence of the articles was, a sample of 773 patients most of them were women with an average age older than 70 years old. CONCLUSIONS: The oral health of patients aged more than 65 is worse than that of the rest population. Long hospital stays or being institutionalized in a residence makes this group susceptible to a worsening of their oral health status. It is necessary to develop protocols for the oral health care of these patients, accompanied by training programs for the personnel responsible.


Assuntos
Hospitalização , Saúde Bucal , Idoso , Feminino , Humanos , Institucionalização , Tempo de Internação , Apoio Social
14.
Aging Clin Exp Res ; 33(9): 2491-2498, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33392982

RESUMO

BACKGROUND: Visual impairment (VI) may lead to worsening functional status and disability. Although disability is very difficult to reverse, it is usually preceded by frailty that may be reverted more easily. It is possible that VI is also related to frailty. AIMS: To assess the relationship between VI and worsening of the frailty status. METHODS: Data were taken from the Toledo Study for Healthy Aging (TSHA), a cohort study of community-dwelling people older than 65 years living in one Spanish province who were followed for 5 years. 1181 participants were included. VI was self-reported and frailty was operationalized using the Fried's phenotype adapted to a Spanish population. Models of multivariate logistic regression were built to assess the associations. RESULTS: The mean age was 73.9 (Standard Deviation (SD) = 5 years) and 58.5% were females. Pre-frailty/frailty prevalence at baseline and follow-up were 41.2/5% and 36.2/12.5%, respectively, and VI was reported by 14.1%. After adjusting for age, gender, education level, tobacco consumption, type 2 diabetes mellitus, high blood pressure, cardiovascular disease, depressive symptoms and cognitive status, odds ratios for the development of frailty by VI were 2.5 (95% Confidence Interval (CI) 1.5-4.4) for non-frail, 2.7 (95% CI 1.3-5.7) for pre-frail and 1.9 (CI 0.6-6.00) for robust participants. The frailty domains whose appearance was most increased by VI were slowness, low energy, low physical activity and weakness. DISCUSSION: Our findings support that VI worsens frailty in the early stages of its development (pre-frailty). VI impairs several frailty items at the same time. CONCLUSIONS: Our study highlights the need to assess both VI and frailty for the prevention of frailty and disability in older people.


Assuntos
Diabetes Mellitus Tipo 2 , Fragilidade , Idoso , Estudos de Coortes , Feminino , Idoso Fragilizado , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Estudos Longitudinais , Autorrelato , Transtornos da Visão/epidemiologia
15.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639008

RESUMO

Background: Mesenchymal stromal cells (MSCs) have the capacity for self-renewal and multi-differentiation, and for this reason they are considered a potential cellular source in regenerative medicine of cartilage and bone. However, research on this field is impaired by the predisposition of primary MSCs to senescence during culture expansion. Therefore, the aim of this study was to generate and characterize immortalized MSC (iMSC) lines from aged donors. Methods: Primary MSCs were immortalized by transduction of simian virus 40 large T antigen (SV40LT) and human telomerase reverse transcriptase (hTERT). Proliferation, senescence, phenotype and multi-differentiation potential of the resulting iMSC lines were analyzed. Results: MSCs proliferate faster than primary MSCs, overcome senescence and are phenotypically similar to primary MSCs. Nevertheless, their multi-differentiation potential is unbalanced towards the osteogenic lineage. There are no clear differences between osteoarthritis (OA) and non-OA iMSCs in terms of proliferation, senescence, phenotype or differentiation potential. Conclusions: Primary MSCs obtained from elderly patients can be immortalized by transduction of SV40LT and hTERT. The high osteogenic potential of iMSCs converts them into an excellent cellular source to take part in in vitro models to study bone tissue engineering.


Assuntos
Células-Tronco Mesenquimais/citologia , Doadores de Tecidos , Idoso , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Células Cultivadas , Expressão Gênica , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Telomerase , Transdução Genética
16.
Bioorg Chem ; 100: 103919, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32417524

RESUMO

Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3ß-acetoxy-hop-22(29)-ene (1), first reported here as natural product, together with 3-oxo-hop-22(29)-ene (2), and 3ß-hydroxy-hop-22(29)-ene (3). ß-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confirmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-inflammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1-3 did not show cytotoxic activity, compound 1 displayed an important inhibitory effect in the mouse ear induced inflammation assay, and significantly inhibited the yeast α-glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-inflammatory properties.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Euphorbiaceae/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antiparasitários/química , Antiparasitários/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Triterpenos/isolamento & purificação , Leveduras/enzimologia , alfa-Glucosidases/metabolismo
17.
Eur J Appl Physiol ; 120(3): 567-577, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048007

RESUMO

PURPOSE: The intensity progression of core stabilization exercises (CSEs) is usually based on personal criteria rather than on objective parameters. To develop exercise progressions for four of the most common CSEs based on the postural control challenge imposed on the participants, and to analyze the effect of participants' sex and postural control level on these progressions. METHODS: Seventy-six males and females performed five variations of front bridge, back bridge, side bridge and bird-dog exercises on two force platforms. The mean velocity of the center of pressure displacement was calculated to assess exercise intensity through the measurement of the participants' body sway (PBS). RESULTS: In general, long bridges produced higher PBS than short bridges, bridging with single leg support produced higher PBS than bridging with double leg support and bridging on a hemisphere ball produced higher PBS than bridging on the floor. The most difficult bridging variations were those performed on a hemisphere ball with single leg support. Regarding the bird-dog, two-point positions produced higher PBS than three-point positions and the positions performed on a hemisphere ball produced higher PBS than those performed on the floor. CONCLUSION: The CSE progressions obtained by males and females were very similar. However, the participants with high trunk control showed less significant differences between exercise variations than the participants with low trunk control, which shows the need to individualize the progressions according to the participants' training level. Overall, this study provides useful information to guide the prescription of CSE progressions in young physically active individuals.


Assuntos
Exercício Físico/fisiologia , Equilíbrio Postural , Tronco/fisiologia , Yoga , Adulto , Feminino , Humanos , Masculino , Caracteres Sexuais , Adulto Jovem
18.
Br J Sports Med ; 54(12): 711-718, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31171515

RESUMO

OBJECTIVE: We performed a systematic review and meta-analysis of epidemiological data of injuries in professional male football. METHOD: Forty-four studies have reported the incidence of injuries in football. Two reviewers independently extracted data and assessed trial quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement and Newcastle Ottawa Scale. Studies were combined in a pooled analysis using a Poisson random effects regression model. RESULTS: The overall incidence of injuries in professional male football players was 8.1 injuries/1000 hours of exposure. Match injury incidence (36 injuries/1000 hours of exposure) was almost 10 times higher than training injury incidence rate (3.7 injuries/1000 hours of exposure). Lower extremity injuries had the highest incidence rates (6.8 injuries/1000 hours of exposure). The most common types of injuries were muscle/tendon (4.6 injuries/1000 hours of exposure), which were frequently associated with traumatic incidents. Minor injuries (1-3 days of time loss) were the most common. The incidence rate of injuries in the top 5 European professional leagues was not different to that of the professional leagues in other countries (6.8 vs 7.6 injuries/1000 hours of exposure, respectively). CONCLUSIONS: Professional male football players have a substantial risk of sustaining injuries, especially during matches.


Assuntos
Traumatismos em Atletas/epidemiologia , Futebol/lesões , Comportamento Competitivo , Humanos , Incidência , Escala de Gravidade do Ferimento , Extremidade Inferior/lesões , Músculo Esquelético/lesões , Recidiva , Fatores de Risco , Traumatismos dos Tendões/epidemiologia
19.
J Strength Cond Res ; 34(12): 3386-3394, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28796125

RESUMO

García-Vaquero, MP, Ruiz-Pérez, I, Barbado, D, and Vera-Garcia, FJ. Electromyographic and kinematic analysis of the flexion-rotation trunk test. J Strength Cond Res 34(12): 3386-3394, 2020-Although most trunk endurance field protocols are performed in the sagittal or frontal planes, the flexion-rotation trunk (FRT) test combines trunk flexion with rotation, which may be relevant to rotation-related sports. The aim of this study was to describe the trunk and hip muscle activation and fatigue and the range of hip flexion of this test. Twenty-seven physically active males and females performed the FRT test after a period of practice. Electromyographic (EMG) signals were bilaterally collected from the rectus abdominis (RA), internal oblique (IO), and rectus femoris (RF), and hip flexion amplitude was measured using a biaxial electrogoniometer. Because the fast Fourier transform algorithm requires stationary EMG signals, subjects performed a 6-second isometric trunk flexion-rotation repetition just before and just after the test execution (preexecution and postexecution repetitions, respectively). Rectus abdominis showed the highest mean activation levels (approximately 30% maximal voluntary isometric contractions [MVC]) in the preexecution repetition, followed by IO (approximately 20% MVC). Also, the mean power frequency (MPF) significantly decreased from the pre-execution to the postexecution repetition for RA and IO, which shows abdominal muscle fatigue. Although each trunk flexion-rotation repetition involved an average 8-14° hip flexion, the RF activation was lower than 10% MVC, and no significant MPF reduction (i.e., no muscle fatigue) was observed for this muscle. In addition, significant negative correlations were found between the FRT test scores and the normalized EMG amplitudes of RF. Based on these results, the FRT test seems a valid field protocol to assess abdominal muscle endurance in trunk flexion-rotation exertions.


Assuntos
Articulação do Quadril/fisiologia , Músculo Esquelético/fisiologia , Rotação , Tronco/fisiologia , Músculos Abdominais/fisiologia , Músculos Abdominais Oblíquos/fisiologia , Fenômenos Biomecânicos , Eletromiografia , Feminino , Humanos , Contração Isométrica/fisiologia , Masculino , Fadiga Muscular/fisiologia , Músculo Quadríceps/fisiologia , Amplitude de Movimento Articular , Reto do Abdome/fisiologia , Torque , Adulto Jovem
20.
Ann Surg ; 270(2): 348-355, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29672416

RESUMO

OBJECTIVE: The aim of this study was to compare and validate the different classifications of severity in acute pancreatitis (AP) and to investigate which characteristics of the disease are associated with worse outcomes. SUMMARY OF BACKGROUND DATA: AP is a heterogeneous disease, ranging from uneventful cases to patients with considerable morbidity and high mortality rates. Severity classifications based on legitimate determinants of severity are important to correctly describe the course of disease. METHODS: A prospective multicenter cohort study involving patients with AP from 23 hospitals in Spain. The Atlanta Classification (AC), Revised Atlanta Classification (RAC), and Determinant-based Classification (DBC) were compared. Binary logistic multivariate analysis was performed to investigate independent determinants of severity. RESULTS: A total of 1655 patients were included; 70 patients (4.2%) died. RAC and DBC were equally superior to AC for describing the clinical course of AP. Although any kind of organ failure was associated with increased morbidity and mortality, persistent organ failure (POF) was the most significant determinant of severity. All local complications were associated with worse outcomes. Infected pancreatic necrosis correlated with high morbidity, but in the presence of POF, it was not associated to higher mortality when compared with sterile necrotizing pancreatitis. Exacerbation of previous comorbidity was associated with increased morbidity and mortality. CONCLUSION: The RAC and DBC both signify an advance in the description and differentiation of AP patients. Herein, we describe the complications of the disease independently associated to morbidity and mortality. Our findings are valuable not only when designing future studies on AP but also for the improvement of current classifications.


Assuntos
Amilases/sangue , Pancreatite Necrosante Aguda/diagnóstico , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/mortalidade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA