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1.
J Sports Sci ; 42(6): 498-510, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38695325

RESUMO

Stair climbing exercise (SE) provides a feasible approach to elevate physical activity, but the effects on metabolic health are unclear. We systematically reviewed the currently available evidence on the effects of SE on fasting and postprandial glycaemia and lipidaemia. Studies were included if they investigated the effects of acute or chronic (at least 2 weeks) SE on fasting and/or postprandial glycaemic (insulin and glucose) and lipidaemic (triacylglycerols and non-esterified fatty acids) responses in healthy, prediabetic or type 2 diabetic adult populations. PubMed, Web of Science and Scopus were searched for eligible studies until July 2022. A total of 25 studies (14 acute and 11 chronic) were eligible for review. Acute bout(s) of SE can reduce postprandial glycaemia in individuals with prediabetes and type 2 diabetes (8 of 9 studies), but not in normoglycemic individuals. The effects of acute SE on postprandial lipidaemic responses and SE training on both fasting and postprandial glycaemia/lipidaemia were unclear. Acute SE may reduce postprandial glucose concentrations in people with impaired glycaemic control, but high-quality studies are needed. More studies are needed to determine the effect of chronic SE training on postprandial glucose and lipid responses, and the acute effects of SE on lipid responses.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Período Pós-Prandial , Subida de Escada , Humanos , Período Pós-Prandial/fisiologia , Glicemia/metabolismo , Subida de Escada/fisiologia , Jejum , Estado Pré-Diabético/terapia , Insulina/sangue , Triglicerídeos/sangue , Ácidos Graxos não Esterificados/sangue , Lipídeos/sangue
2.
Eur J Appl Physiol ; 124(2): 445-455, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37543544

RESUMO

INTRODUCTION: It is unknown whether predetermined (un)interrupted sitting within a laboratory setting will induce compensatory changes in human behaviours (energy intake and physical activity) once people return to a free-living environment. The effects of breaking up prolonged sitting on cognition are also unclear. METHODS: Twenty-four (male = 13) healthy participants [age 31 ± 8 y, BMI 22.7 ± 2.3 kg/m2 (mean ± SD)] completed 320 min mixed-feeding trials under prolonged sitting (SIT) or with 2 min walking at 6.4 km/h every 20 min (ACTIVE), in a randomised crossover design. Human behaviours were recorded post-trial under free-living conditions until midnight. Cognitive performance was evaluated before and immediately after SIT and ACTIVE trials. Self-perceived sensations (appetite, energy and mood) and finger prick blood glucose levels were collected at regular intervals throughout the trials. RESULTS: There were no differences between trials in eating behaviour and spontaneous physical activity (both, p > 0.05) in free-living conditions, resulting in greater overall total step counts [11,680 (10740,12620) versus 6049 (4845,7253) steps] and physical activity energy expenditure (PAEE) over 24-h period in ACTIVE compared to SIT (all, p < 0.05). Greater self-perceived levels of energy and lower blood glucose iAUC were found in ACTIVE trial compared to SIT trial (both, p < 0.05). No differences were found in cognitive performance between trials (all, p > 0.05). CONCLUSION: Breaking up sitting does not elicit subsequent behavioural compensation, resulting in greater 24-h step counts and PAEE in healthy adults. Breaking up sitting reduces postprandial glucose concentrations and elicits greater self-perceived energy levels, but these positive effects do not acutely translate into improved cognitive function.


Assuntos
Glicemia , Postura Sentada , Adulto , Humanos , Masculino , Adulto Jovem , Comportamento Sedentário , Exercício Físico , Caminhada , Cognição , Fadiga , Estudos Cross-Over , Período Pós-Prandial , Insulina
3.
Psychol Sport Exerc ; 70: 102531, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37837841

RESUMO

Both acute aerobic (AE) and resistance exercise (RE) have been acknowledged to be effective methods in enhancing executive function and brain-related P3 amplitudes. Nevertheless, the effect of acute concurrent exercise training (CET), combining both AE and RE, on executive function remains subject to speculation. Moreover, investigation of the mechanisms that underlie improvements in executive function would facilitate scientific understanding. Notably, lactate has emerged as a candidate among several potential mechanisms. Therefore, the main aim of the present study was to investigate the effect of acute CET on the cognitive flexibility dimension of executive function using behavioural and neuro-electric measures. A secondary aim was to determine the mediating effect of blood lactate in the acute exercise-executive function relationship. Seventy-eight young adults (38 women, 40 men; 22.8 ± 1.8 years) were randomly assigned to one of the following groups: CET, AE, or reading control (RC). Cognitive flexibility was evaluated using the Task-Switching Test and its derived electroencephalography (EEG) was assessed immediately prior to and following each treatment. Fingertip lactate assays were taken prior to, at the midpoint, and after each treatment. Both acute CET and AE shortened response time regardless of test conditions when compared to the RC group. Greater P3 amplitude was observed following CET in the heterogeneous condition and under AE in the switch condition. A significant mediation of blood lactate for response time emerged in both the CET and AE groups for the heterogeneous and switch conditions. The blood lactate mediation was not reflected in P3 amplitude. The present findings suggest that acute CET leads to positive behavioural and neuro-electric alterations of cognitive flexibility, and its effect is similar to AE. Additionally, blood lactate serves as a mediator of the effects of acute exercise on executive function from a behavioural, but not neuro-electric standpoint.


Assuntos
Função Executiva , Ácido Láctico , Masculino , Adulto Jovem , Humanos , Feminino , Função Executiva/fisiologia , Exercício Físico/fisiologia , Eletroencefalografia , Encéfalo/fisiologia
4.
Osteoporos Int ; 34(10): 1729-1737, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37326685

RESUMO

In this multi-institutional retrospective cohort study, we compared the long-term risk of osteonecrosis of the jaw following the use of denosumab vs. bisphosphonates in osteoporotic patients. After 2-year use, the likelihood of osteonecrosis of the jaw is lower with denosumab compared to bisphosphonates, and the difference increases with time. PURPOSE: To compare the long-term risk of osteonecrosis of the jaw (ONJ) between osteoporotic patients treated with bisphosphonates (BPs) and denosumab. METHODS: This multi-institutional retrospective cohort study included patients aged > 40 years with osteoporosis between January 2010 and December 2018. Patients who met the eligibility criteria were divided into BPs and denosumab groups by propensity score matching (PSM). The risk of ONJ of denosumab vs. BPs was estimated using a Cox proportional hazards model and was described by the cumulative incidence rate using the Kaplan-Meier method. RESULTS: A total of 84,102 patients with osteoporosis were enrolled, among whom, 8962 were eligible for inclusion based on their first-line drug use (denosumab, n = 3,823; BPs, n = 5,139). Following PCM matching (1:1), the BPs and denosumab groups included 3665 patients each. The incidence density of ONJ in the denosumab and BPs matching groups was 1.47 vs. 2.49 events (per 1000 person-years), respectively. The hazard ratio of ONJ in the denosumab vs. BPs group was estimated as 0.581 (95% confidence interval: 0.33-1.04, p = 0.07). The cumulative incidence rates of ONJ in both groups were similar for the first and second years of drug use (p = 0.062), but significantly different from the third year onwards (p = 0.022). The severity of ONJ was not significantly different between the two groups. CONCLUSION: In osteoporotic patients, after 2 years of use, the likelihood of ONJ being induced by denosumab is lower than that of BPs, and the difference increases with time.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteonecrose , Osteoporose , Humanos , Difosfonatos/efeitos adversos , Denosumab/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Osteonecrose/induzido quimicamente , Osteoporose/complicações , Fatores de Risco , Conservadores da Densidade Óssea/efeitos adversos
5.
Am J Clin Nutr ; 118(1): 132-140, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37080462

RESUMO

BACKGROUND: Polymerized polyphenols (PP) found in oolong tea can inhibit pancreatic lipase activity in vitro, and pilot work indicates that this may reduce postprandial lipemia. Since tea contains caffeine and catechins, the interactions between these ingredients and PP warrant investigation. OBJECTIVES: To assess whether PP ingested alone or with caffeine and catechins lowers postprandial lipemia. METHODS: Fifty healthy adults [mean (SD) age: 26 (7) y; BMI (in kg/m2): 24.0 (2.7); female: n = 16] completed 4 oral lipid tolerance tests in a placebo-controlled randomized, crossover design. Participants ingested 40 g of fat with either 1) placebo, 2) 100 mg PP, 3) 150 mg PP, or 4) 100 mg PP plus 50 mg caffeine and 63 mg catechins (PP + CC). Blood was sampled for 3 h postprandially to assess concentrations of serum and plasma triacylglycerol and plasma markers of lipid (NEFA; glycerol; LDL and HDL cholesterol; and ApoA-I, A-II, B, C-II, C-III, and E) and glucose metabolism (glucose, insulin, and C-peptide). RESULTS: Serum and plasma triacylglycerol concentrations and lipid metabolism variables generally increased following any test drink ingestion (main effect of time, p < 0.001). Nevertheless, for the lipid metabolism responses, there were no statistically significant condition-time interactions and no statistically significant differences in incremental or total area under the curve between conditions, apart from HDL cholesterol (p = 0.021). Ingesting 100 mg PP + CC lowered peak plasma glucose, insulin, and C-peptide concentrations compared with all other conditions 30 min postingestion (p < 0.001), with persistent alterations in glucose concentrations observed for 90 min compared with placebo and 100 mg PP conditions. CONCLUSIONS: PP ingested at doses ≤150 mg does not clearly alter early-phase postprandial triacylglycerol concentrations in healthy adults, irrespective of the presence or absence of caffeine and catechins. Nevertheless, caffeine and catechins added to PP lowered postprandial glucose and insulin concentrations. This trial was registered in ClinicalTrials.gov as NCT03324191 (https://clinicaltrials.gov/ct2/show/NCT03324191).


Assuntos
Catequina , Polifenóis , Humanos , Adulto , Feminino , Polifenóis/farmacologia , Estudos Cross-Over , Cafeína , HDL-Colesterol , Glicemia/metabolismo , Peptídeo C , Triglicerídeos , Glucose , Insulina , Catequina/farmacologia , Chá , Ingestão de Alimentos , Período Pós-Prandial
6.
Bot Stud ; 64(1): 5, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36890306

RESUMO

BACKGROUND: The aim of this study was to determine the actual state of the photosynthetic apparatus and exhibit distinguishable differences in the chlorophyll fluorescence (ChlF) components in different seedling ages of M. oiwakensis plants subjected to different light intensity (LI). Potted 6-month-old greenhouse seedlings and field collected 2.4-year-old seedlings with 5 cm heights were selected and randomly separated into seven groups for photosynthesis measurements illuminated with 50, 100 (assigned as low LI), 300, 500, 1,000 (as moderate LI), 1,500 and 2,000 (as high LI) µmol m-2 s-1 photosynthetic photon flux density (PPFD) treatments. RESULTS: n 6-month-old seedlings, as LI increased from 50 to 2,000 PPFD, the values of non-photochemical quenching and photo-inhibitory quenching (qI) increased but potential quantum efficiency of PSII (Fv/Fm) and photochemical efficiency of photosystem II (ΦPSII) values decreased. High electron transport rate and percentage of actual PSII efficiency by Fv/Fm values were observed in 2.4-year-old seedlings at high LI conditions. Furthermore, higher ΦPSII was detected under low LI conditions, with lower energy-dependent quenching (qE) and qI values and photo-inhibition % decreased as well. However, qE and qI increased as ΦPSII decreased and photo-inhibition% increased under high LI treatments. CONCLUSIONS: These results could be useful for predicting the changes in growth and distribution of Mahonia species grown in controlled environments and open fields with various combinations of varying light illuminations, and ecological monitoring of their restoration and habitat creation is important for provenance conservation and helps to formulate better conservation strategies for the seedlings.

7.
FASEB J ; 37(4): e22846, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36856983

RESUMO

Colchicine is a broad-acting anti-inflammatory agent that has attracted interest for repurposing in atherosclerotic cardiovascular disease. Here, we studied its ability at a human equivalent dose of 0.5 mg/day to modify plaque formation and composition in murine atherosclerosis and investigated its actions on macrophage responses to atherogenic stimuli in vitro. In atherosclerosis induced by high-cholesterol diet, Apoe-/- mice treated with colchicine had 50% reduction in aortic oil Red O+ plaque area compared to saline control (p = .001) and lower oil Red O+ staining of aortic sinus lesions (p = .03). In vitro, addition of 10 nM colchicine inhibited foam cell formation from murine and human macrophages after treatment with oxidized LDL (ox-LDL). Mechanistically, colchicine downregulated glycosylation and surface expression of the ox-LDL uptake receptor, CD36, and reduced CD36+ staining in aortic sinus plaques. It also decreased macrophage uptake of cholesterol crystals, resulting in lower intracellular lysosomal activity, inhibition of the NLRP3 inflammasome, and reduced secretion of IL-1ß and IL-18. Colchicine's anti-atherosclerotic actions were accentuated in a mouse model of unstable plaque induced by carotid artery tandem stenosis surgery, where it decreased lesion size by 48% (p = .01), reduced lipid (p = .006) and necrotic core area (p = .007), increased collagen content and cap-to-necrotic core ratio (p = .05), and attenuated plaque neutrophil extracellular traps (p < .001). At low dose, colchicine's effects were not accompanied by the evidence of microtubule depolymerization. Together, these results show that colchicine exerts anti-atherosclerotic and plaque-stabilizing effects at low dose by inhibiting foam cell formation and cholesterol crystal-induced inflammation. This provides a new framework to support its repurposing for atherosclerotic cardiovascular disease.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Estenose das Carótidas , Humanos , Animais , Camundongos , Células Espumosas , Colchicina , Colesterol
8.
Commun Biol ; 6(1): 265, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36914713

RESUMO

Atherosclerotic plaque rupture leading to myocardial infarction is a major global health burden. Applying the tandem stenosis (TS) mouse model, which distinctively exhibits the characteristics of human plaque instability/rupture, we use quantitative proteomics to understand and directly compare unstable and stable atherosclerosis. Our data highlight the disparate natures and define unique protein signatures of unstable and stable atherosclerosis. Key proteins and pathway networks are identified such as the innate immune system, and neutrophil degranulation. The latter includes calprotectin S100A8/A9, which we validate in mouse and human unstable plaques, and we demonstrate the plaque-stabilizing effects of its inhibition. Overall, we provide critical insights into the unique proteomic landscape of unstable atherosclerosis (as distinct from stable atherosclerosis and vascular tissue). We further establish the TS model as a reliable preclinical tool for the discovery and testing of plaque-stabilizing drugs. Finally, we provide a knowledge resource defining unstable atherosclerosis that will facilitate the identification and validation of long-sought-after therapeutic targets and drugs for plaque stabilization.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Animais , Camundongos , Placa Aterosclerótica/tratamento farmacológico , Proteômica , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/metabolismo , Modelos Animais de Doenças
10.
Med Sci Sports Exerc ; 54(7): 1183-1189, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35389963

RESUMO

INTRODUCTION: Continuous exercise can increase postprandial gut hormone such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) responses, but it is unknown whether interrupting prolonged sitting with intermittent walking elicits this effect. METHOD: Ten participants with central overweight/obesity (7 men and 3 postmenopausal women, 51 ± 5 yr; mean ± SD) completed a randomized crossover study in which they consumed breakfast and lunch in the laboratory while either sitting continuously for the entire 5.5-h period (SIT) or the prolonged sitting interrupted every 20 min by walking briskly (6.4 km·h-1) for 2 min (BREAKS). Blood samples were collected at regular intervals to examine postprandial plasma GLP-1, PYY, and glucose-dependent insulinotropic polypeptide concentrations. Adipose tissue samples were collected at baseline and at the end of the trials to examine changes in net dipeptidyl peptidase 4 secretion from primary explants. RESULTS: Mean (95% confidence interval) postprandial GLP-1 and PYY incremental area under curve values were elevated by 26% and 31% in the BREAKS trial versus SIT (8.4 [0.7, 16.1] vs 6.7 [-0.8, 14.2], P = 0.001, and 26.9 [8.1, 45.6] vs 20.4 [5.1, 35.8] nmol·330 min·L-1, P = 0.024, respectively) but without any such effect on glucose-dependent insulinotropic polypeptide (P = 0.076) or net adipose tissue dipeptidyl peptidase 4 secretion (P > 0.05). CONCLUSIONS: Interrupting prolonged sitting with regular short bouts of brisk walking increases postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity.


Assuntos
Glicemia , Dipeptidil Peptidase 4 , Estudos Cross-Over , Feminino , Peptídeo 1 Semelhante ao Glucagon , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Obesidade , Obesidade Abdominal , Peptídeo YY , Período Pós-Prandial , Caminhada/fisiologia
11.
BMJ Open ; 12(3): e050458, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35292487

RESUMO

OBJECTIVES: To review the current evidence on the acute effects of interrupting prolonged periods of sitting with intermittent physical activity (PA) on cognition in healthy populations. DESIGN: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. METHODS: Studies were included if they investigated the acute effects of taking regular PA breaks from sitting on cognition in healthy populations without any cardiovascular disease, history of brain injury, or psychiatric or neurological disorder. Four electronic databases-PubMed, Scopus, MEDLINE and ProQuest-were searched for eligible studies on 20 September 2020. Study quality was assessed using the Physiotherapy Evidence Database scale. RESULTS: Seven studies, involving 168 participants aged between 18 and 80 years, were eligible for inclusion in this review. Three of the seven studies found positive effects of interrupting sitting with either (a) 3 min of relatively high-intensity (6 km/hour) walking every 30 min on attention and inhibitory control in young adults; (b) hourly breaks with progressively longer duration (10-30 min) of very light-intensity cycling/walking on attention, working memory and cognitive flexibility in adults with obesity; or (c) an initial bout of continuous moderate-intensity exercise, followed by interruption of post-exercise sitting with 3 min breaks of light-intensity walking (3.2 km/hour) every 30 min, on working memory in older adults with overweight. CONCLUSION: Given the limited evidence with mixed findings on this topic in the literature and the heterogeneity of PA protocols across the included studies, the results regarding the effectiveness of interrupting prolonged sitting with PA breaks in improving cognition warrant further verification. PROSPERO REGISTRATION NUMBER: CRD42020147536.


Assuntos
Glicemia , Comportamento Sedentário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição , Estudos Cross-Over , Exercício Físico , Humanos , Pessoa de Meia-Idade , Sobrepeso/psicologia , Caminhada , Adulto Jovem
12.
Small ; 18(17): e2107032, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35229467

RESUMO

Multimodal microendoscopes enable co-located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high-sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high-quality multiple modalities simultaneously. An optical design is demonstrated which uses two-photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens-in-lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber-optic design approaches. This lens-in-lens is then integrated into an intravascular catheter probe with a diameter of 520 µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.


Assuntos
Fótons , Tomografia de Coerência Óptica , Animais , Tecnologia de Fibra Óptica , Camundongos , Imagem Óptica , Impressão Tridimensional , Tomografia de Coerência Óptica/métodos
13.
J Formos Med Assoc ; 121(9): 1721-1727, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35000824

RESUMO

BACKGROUND/PURPOSE: GP.Mur is a clinically important red blood cell (RBC) type. GP.Mur and band 3 interact on the RBCs. We previously observed that healthy adults with GP.Mur type present slightly higher blood pressure (BP). Because band 3 and Hb comodulate nitric oxide (NO)-dependent vasodilation and hemoglobin (Hb) is positively associated with BP, we aimed to test whether these could contribute to higher BP in GP.Mur+ people. METHODS: We recruited 989 non-elderly adults (21% GP.Mur) free of catastrophic illness and not on cardiovascular or anti-hypertensive medication. Their body indices, blood lab data and lifestyle data were collected for analyses of potential BP-related factors (BMI, age, smoking, Hb, and GP.Mur). RESULTS: BMI and age remained the most significant contributors to BP. GP.Mur slightly increased systolic BP (SBP). The direct correlation between Hb and BP was only found in Taiwanese non-anemic men, not women. After age and BMI adjusted, we estimated an increase of 1.8 mmHg and 2.6 mmHg of SBP by 1 g/dL Hb among men without and with GP.Mur type, respectively. Hb was generally lower among people expressing GP.Mur, which likely limited their larger impact on BP. CONCLUSION: GP.Mur contributed to BP in both Hb-dependent and Hb-independent fashion. A pronounced impact of hemoglobin on BP likely requires sufficient Hb, as GP.Mur increased the sensitivity of SBP to Hb only in non-anemic Taiwanese men, and not in Taiwanese women or anemic men. The mechanism through which GP.Mur affected BP independent of Hb is unknown.


Assuntos
Glicoforinas , Hipertensão , Adulto , Pressão Sanguínea , Eritrócitos , Feminino , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade
14.
Thromb Haemost ; 122(2): 196-207, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34619795

RESUMO

BACKGROUND: 3F7 is a monoclonal antibody targeting the enzymatic pocket of activated factor XII (FXIIa), thereby inhibiting its catalytic activity. Given the emerging role of FXIIa in promoting thromboinflammation, along with its apparent redundancy for hemostasis, the selective inhibition of FXIIa represents a novel and highly attractive approach targeting pathogenic processes that cause thromboinflammation-driven cardiovascular diseases. METHODS: The effects of FXIIa inhibition were investigated using three distinct mouse models of cardiovascular disease-angiotensin II-induced abdominal aortic aneurysm (AAA), an ApoE-/- model of atherosclerosis, and a tandem stenosis model of atherosclerotic plaque instability. 3F7 or its isotype control, BM4, was administered to mice (10 mg/kg) on alternate days for 4 to 8 weeks, depending on the experimental model. Mice were examined for the development and size of AAAs, or the burden and instability of atherosclerosis and associated markers of inflammation. RESULTS: Inhibition of FXIIa resulted in a reduced incidence of larger AAAs, with less acute aortic ruptures and an associated fibro-protective phenotype. FXIIa inhibition also decreased stable atherosclerotic plaque burden and achieved plaque stabilization associated with increased deposition of fibrous structures, a >2-fold thicker fibrous cap, increased cap-to-core ratio, and reduction in localized and systemic inflammatory markers. CONCLUSION: Inhibition of FXIIa attenuates disease severity across three mouse models of thromboinflammation-driven cardiovascular diseases. Specifically, the FXIIa-inhibiting monoclonal antibody 3F7 reduces AAA severity, inhibits the development of atherosclerosis, and stabilizes vulnerable plaques. Ultimately, clinical trials in patients with cardiovascular diseases such as AAA and atherosclerosis are warranted to demonstrate the therapeutic potential of FXIIa inhibition.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Aneurisma da Aorta Abdominal/prevenção & controle , Aterosclerose/prevenção & controle , Fator XIIa/antagonistas & inibidores , Placa Aterosclerótica/metabolismo , Animais , Aneurisma da Aorta Abdominal/epidemiologia , Apolipoproteínas E , Modelos Animais de Doenças , Inflamação , Masculino , Camundongos
15.
J Physiol ; 600(4): 921-947, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33895996

RESUMO

KEY POINTS: Ageing is associated with increased systemic inflammation and metabolic dysfunction that contributes to the development of age-associated diseases. The role of adipose tissue in immunometabolic alterations that take place with ageing is unknown in humans. We show, in healthy, active and lean older adults, that adipose tissue, but not skeletal muscle, displays considerable pro-inflammatory transcriptomic, cellular and secretory changes, as well as a reduction in insulin signalling proteins compared to younger adults. These findings indicate that adipose tissue undergoes substantial immunometabolic alterations with ageing, and that these changes are tissue-specific and more profound than those observed in skeletal muscle or in the circulation. These results identify adipose tissue as an important tissue in the biological ageing process in humans, which may exhibit signs of immunometabolic dysfunction prior to systemic manifestation. ABSTRACT: Ageing and obesity are both characterized by inflammation and a deterioration in metabolic health. It is now clear that adipose tissue plays a major role in inflammation and metabolic control in obesity, although little is known about the role of adipose tissue in human ageing. To understand how ageing impacts adipose tissue, we characterized subcutaneous adipose tissue and skeletal muscle samples from twelve younger (27 ± 4 years [Young]) and twelve older (66 ± 5 years [Old]) active/non-obese males. We performed a wide-range of whole-body and tissue measures, including RNA-sequencing and multicolour flow cytometry. We also measured a range of inflammatory and metabolic proteins in the circulation and their release by adipose tissue, ex vivo. Both adipose tissue and muscle had ∼2-fold more immune cells per gram of tissue with ageing. In adipose tissue, this immune cell infiltration was driven by increased memory/effector T-cells, whereas, in muscle, the accumulation was driven by memory/effector T-cells and macrophages. Transcriptomic analysis revealed that, with ageing, adipose tissue, but not muscle, was enriched for inflammatory transcripts/pathways related to acquired and innate immunity. Ageing also increased the adipose tissue pro-inflammatory secretory profile. Insulin signalling protein content was reduced in adipose tissue, but not muscle. Our findings indicate that adipose tissue undergoes substantial immunometabolic changes with ageing in humans, and that these changes are tissue-specific and more profound than those observed in the circulation and skeletal muscle.


Assuntos
Resistência à Insulina , Tecido Adiposo/metabolismo , Idoso , Envelhecimento , Humanos , Masculino , Músculo Esquelético/metabolismo , Obesidade/metabolismo
16.
J Am Heart Assoc ; 11(1): e022761, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34970931

RESUMO

Background Diabetes is known to accelerate atherosclerosis and increase plaque instability. However, there has been a lack of suitable animal models to study the effect of diabetes on plaque instability. We hypothesized that the tandem stenosis mouse model, which reflects plaque instability/rupture as seen in patients, can be applied to study the effects of diabetes and respective therapeutics on plaque instability/rupture. Methods and Results ApoE-/- mice at 7 weeks of age were rendered diabetic with streptozotocin and 5 weeks later were surgically subjected to tandem stenosis in the right carotid artery and fed with a high-fat diet for 7 weeks. As a promising new antidiabetic drug class, a sodium glucose co-transporter 2 inhibitor was tested in this new model. Diabetic mice showed an increase in the size of unstable atherosclerotic plaques and in the plaque instability markers MCP-1, CD68, and necrotic core size. Mice treated with dapagliflozin demonstrated attenuated glucose and triglyceride levels. Importantly, these mice demonstrated plaque stabilization with enhanced collagen accumulation, increased fibrosis, increased cap-to-lesion height ratios, and significant upregulation of the vasculoprotective NADPH oxidase 4 expression. Conclusions The tandem stenosis mouse model in combination with the application of streptozotocin represents a highly suitable and unique mouse model for studying plaque destabilization under diabetic conditions. Furthermore, for the first time, we provide evidence of plaque-stabilizing effects of sodium-glucose co-transporter 2 inhibitor. Our data also suggest that this newly developed mouse model is an attractive preclinical tool for testing antidiabetic drugs for the highly sought-after potential to stabilize atherosclerotic plaques.


Assuntos
Diabetes Mellitus Experimental , Placa Aterosclerótica , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Compostos Benzidrílicos , Constrição Patológica , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Glucose , Glucosídeos , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Camundongos , Placa Aterosclerótica/patologia , Sódio/metabolismo , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Estreptozocina/uso terapêutico
17.
Appl Physiol Nutr Metab ; : 1-7, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403626

RESUMO

It is unclear whether neuromuscular electrical stimulation (NMES) has meaningful metabolic effects when users have the opportunity to self-select the intensity to one that can be comfortably tolerated. Nine healthy men aged 28 ± 9 y (mean ± SD) with a body mass index 22.3 ± 2.3 kg/m2 completed 3 trials involving a 2-h oral glucose tolerance test whilst, in a randomised counterbalanced order, (1) sitting motionless (SIT), (2) standing motionless (STAND); and (3) sitting motionless with NMES of quadriceps and calves at a self-selected tolerable intensity. The mean (95% confidence interval [CI]) total energy expenditure was greater in the NMES trial (221 [180-262] kcal/2 h) and STAND trial (178 [164-191] kcal/2 h) than during SIT (159 [150-167] kcal/2 h) (both, p < 0.05). This was primarily driven by an increase in carbohydrate oxidation in the NMES and STAND trials compared with the SIT trial (p < 0.05). Postprandial insulin iAUC was lower in both NMES and STAND compared with SIT (16.4 [7.7-25.1], 17 [7-27] and 22.6 [10.8-34.4] nmol·120 min/L, respectively; both, p < 0.05). Compared with sitting, both NMES and STAND increased energy expenditure and whole-body carbohydrate oxidation and reduced postprandial insulin concentrations in healthy men, with more pronounced effects seen with NMES. Self-selected NMES is a potential strategy for improving metabolic health. This trial is registered at ClinicalTrials.gov (ID: NCT04389736). Novelty: NMES at a comfortable intensity enhances energy expenditure and carbohydrate oxidation, and reduces postprandial insulinemia. Thus, self-selected NMES represents a potential strategy to improve metabolic health.

18.
BMC Womens Health ; 21(1): 275, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325678

RESUMO

BACKGROUND: One-handed backhand (OB) and two-handed backhand (TB) styles are commonly used in tennis, but only TB generates loadings on the non-dominant arm and a greater extension torque on the rear leg, leading to a greater axial torque involving rotation of the hip and trunk. The current study investigated whether those effects can further affect bone area (BA), bone mineral content (BMC) and density (BMD) in postmenopausal recreational tennis players. METHODS: BA, BMC and BMD of the lumbar spine, hip and distal radius were assessed using dual-energy X-ray absorptiometry in TB, OB, and swimmers' group as a control (SG) (all participants self-reported for at least 5 years of exercise history, n = 14 per group). Muscular strength was assessed with a hand dynamometer. Among these three groups, the BA, BMC and BMD of distal radius and muscle strength were assessed using one-way ANOVA, and those of the lumbar region and the hip joint were tested by one-way ANCOVA. RESULTS: TB showed higher BMC and BMD for both lumbar spine and femoral neck than SG (all, p < 0.05). Both OB and TB showed greater BMD inter-trochanter than SG (both, p < 0.05). OB demonstrated greater inter-arm differences in the distal radius, which involved 1/3 distal for BMC and mid-distal radius for BMD compared to the TB and SG (all, p < 0.05). In addition, greater inter-arm asymmetry of grip strength was found in OB compared to TB and SG (both, p < 0.05). CONCLUSION: For postmenopausal women, performing two-handed backhand strokes, leads to higher BMC and BMD in the non-dominant arm, the lumbar region, and hips, indicating potential benefit to maintain bone health and strength. Whether this result leads to reducing the risk of osteoporosis needs to be investigated in further research.


Assuntos
Densidade Óssea , Tênis , Absorciometria de Fóton , Estudos Transversais , Feminino , Humanos , Projetos Piloto , Pós-Menopausa
19.
Sci Transl Med ; 13(598)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135111

RESUMO

Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150; n = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75; n = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200; n = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (-1.91 ± 0.99 kilograms) almost entirely due to fat loss (-1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (-1.60 ± 1.06 kilograms; P = 0.46 versus 75:75) but with attenuated reductions in body fat (-0.74 ± 1.32 kilograms; P = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (-0.52 ± 1.09 kilograms; P ≤ 0.04 versus 75:75 and 0:150) or fat mass (-0.12 ± 0.68 kilograms; P ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups (P > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health.


Assuntos
Jejum , Redução de Peso , Adulto , Composição Corporal , Peso Corporal , Restrição Calórica , Ingestão de Energia , Metabolismo Energético , Humanos , Obesidade
20.
Healthcare (Basel) ; 9(6)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067379

RESUMO

Acupuncture-type interventions (such as moxibustion and acupuncture) at Bladder 67 (BL67, Zhiyin point) have been proposed to have positive effects on breech presentation. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of moxibustion and acupuncture in correcting breech presentation. We searched PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Electronic Periodical Services (CEPS), and databases at ClinicalTrials.gov to identify relevant randomized controlled trials (RCTs). In this study, sixteen RCTs involving 2555 participants were included. Compared to control, moxibustion significantly increased cephalic presentation at birth (RR = 1.39; 95% CI = 1.21-1.58). Moxibustion also seemed to elicit better clinical outcomes in the Asian population (RR = 1.42; 95% CI = 1.21-1.67) than in the non-Asian population (RR = 1.20; 95% CI = 1.01-1.43). The effects of acupuncture on correcting breech presentation after sensitivity analysis were inconsistent relative to control. The effect of moxibustion plus acupuncture was synergistic for correcting breech presentation (RR = 1.53; 95% CI = 1.26-1.86) in one RCT. Our findings suggest that moxibustion therapy has positive effects on correcting breech presentation, especially in the Asian population.

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