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Stem Cells Translational Medicine Jun 2024Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases...
Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases oxygen consumption of islets and enhances insulin secretion. However, the underlying mechanism for the protective role of MSCs in α-cell mitochondrial dysfunction remains unclear. Here, human umbilical cord MSCs (hucMSCs) were used to treat 2 kinds of T2DM mice and αTC1-6 cells to explore the role of hucMSCs in improving α-cell mitochondrial dysfunction and hyperglucagonemia. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function of α cells was assessed by the Seahorse Analyzer. To investigate the underlying mechanisms, Sirtuin 1 (SIRT1), Forkhead box O3a (FoxO3a), glucose transporter type1 (GLUT1), and glucokinase (GCK) were assessed by Western blotting analysis. In vivo, hucMSC infusion improved glucose and insulin tolerance, as well as hyperglycemia and hyperglucagonemia in T2DM mice. Meanwhile, hucMSC intervention rescued the islet structure and decreased α- to β-cell ratio. Glucagon secretion from αTC1-6 cells was consistently inhibited by hucMSCs in vitro. Meanwhile, hucMSC treatment activated intracellular SIRT1/FoxO3a signaling, promoted glucose uptake and activation, alleviated mitochondrial dysfunction, and enhanced ATP production. However, transfection of SIRT1 small interfering RNA (siRNA) or the application of SIRT1 inhibitor EX-527 weakened the therapeutic effects of hucMSCs on mitochondrial function and glucagon secretion. Our observations indicate that hucMSCs mitigate mitochondrial dysfunction and glucagon hypersecretion of α cells in T2DM via SIRT1/FoxO3a signaling, which provides novel evidence demonstrating the potential for hucMSCs in treating T2DM.
PubMed: 38864709
DOI: 10.1093/stcltm/szae038 -
Agreement of Air Bike and Treadmill Protocols to Assess Maximal Oxygen Uptake: An Exploratory Study.International Journal of Exercise... 2024Maximal oxygen consumption (V̇O) is an important measure of aerobic fitness, with applications in evaluating fitness, designing training programs, and assessing overall...
Maximal oxygen consumption (V̇O) is an important measure of aerobic fitness, with applications in evaluating fitness, designing training programs, and assessing overall health. While treadmill assessments are considered the gold standard, airbikes (ABs) are increasingly popular exercise machines. However, limited research exists on AB-based V̇O2max assessments, particularly regarding agreement with treadmill graded exercise tests. To address this gap, a randomized crossover study was conducted, involving 15 healthy adults (9M, 6F, 7 familiar with AB) aged 30.1 ± 8.6 years. Paired -tests, intraclass correlation coefficients (ICC), Bland-Altman and Principal component (PC) analyses were used to assess agreement between protocols. The results demonstrated good to excellent agreement in V̇O, maximum heart rate (HR), and rating of perceived exertion (ICC range: 0.89-0.92). However, significant differences were observed in several measures, including V̇O and maximum HR ( < 0.01). Overall a systematic bias 3.31 mL/kg/min (treadmill > AB, 95%CI[1.67,4.94]) was observed, no proportional bias was present; however, regular AB users (systematic bias: 1.27 (95%CI[0.20,2.34]) mL/kg/min) exhibited higher agreement in V̇O measures compared to non-regular users (systematic bias: 5.09 (95%CI[3.69,6.49]) mL/kg/min). There were no significant differences in cardiorespiratory coordination, between the AB and the treadmill. These findings suggest that for individuals familiar with the AB, it can be a suitable alternative for assessing V̇O compared to the treadmill. Future research with larger samples should focus on developing prediction equations for field AB tests to predict V̇O. Practitioners should consider using the AB to assess V̇O in individuals who prefer it over running.
PubMed: 38863601
DOI: No ID Found -
Chronic Respiratory Disease 2024The effects of coronavirus disease 2019 (COVID-19) on the cardiorespiratory fitness of hospitalized and obese patients are of utmost relevance. This study aimed to...
BACKGROUND
The effects of coronavirus disease 2019 (COVID-19) on the cardiorespiratory fitness of hospitalized and obese patients are of utmost relevance. This study aimed to analyze how hospital and intensive care unit (ICU) stay together with body mass index affect cardiorespiratory fitness in patients with COVID-19.
METHODS
251 participants (males, = 118; females, = 133) were assigned to four groups: non-hospitalized COVID-19 patients ( = 65, age: 45.3 years), hospitalized COVID-19 patients ( = 63, age: 57.6 years), COVID-19 patients admitted to the ICU ( = 61, age: 56.9 years), and control group ( = 62, age: 49.8 years). An incremental cardiopulmonary exercise test was performed between 3 and 6 weeks after medical discharge from hospital.
RESULTS
Higher peak oxygen uptake (VO), ventilatory efficiency and power output were found in ICU patients with normal weight (NW) than in overweight (OW) (Mean difference: 0.1 L·min, -5.5, 29.0 W, respectively) and obese (OB) ICU patients (Mean difference: 0.1 L·min, -5.0, 26.2 W, respectively) ( < .05). In NW, OW and OB participants, higher VO and power output were observed in control group compared with non-hospitalized (Mean difference: NW: 0.2 L·min, 83.3 W; OW: 0.2 L·min, 60.0 W; OB: 0.2 L·min, 70.9 W, respectively), hospitalized (Mean difference: NW: 0.2 L·min, 72.9 W; OW: 0.1 L·min, 58.3 W; OB: 0.2 L•min, 91.1 W, respectively) and ICU patients (Mean difference: NW: 0.1 L·min, 70.9 W; OW: 0.2 L·min, 91.1 W; OB: 0.3 L·min; 65.0 W, respectively) ( < .05).
CONCLUSIONS
The degree of severity of COVID-19, especially identified by hospitalization and ICU stay, together with obesity and overweight were key factors in reducing cardiorespiratory fitness in patients with COVID-19.
Topics: Humans; COVID-19; Female; Male; Middle Aged; Body Mass Index; Cardiorespiratory Fitness; Intensive Care Units; Obesity; Length of Stay; SARS-CoV-2; Exercise Test; Oxygen Consumption; Adult; Hospitalization; Aged; Overweight
PubMed: 38863283
DOI: 10.1177/14799731241259749 -
Arthritis Research & Therapy Jun 2024In gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1β. This study aimed to...
OBJECTIVE
In gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1β. This study aimed to investigate the role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU.
METHODS
BMDM from WT and CD11b KO mice were stimulated in vitro with MSU crystals. Cellular supernatants were collected to assess the expression of the inflammatory cytokines by enzyme-linked immunosorbent assay and western blot methods. The role of integrin CD11b in MSU-induced gouty arthritis in vivo was investigated by intra-articular injection of MSU crystals. Real-time extracellular acidification rate and oxygen consumption rate of BMDMs were measured by Seahorse Extracellular Flux Analyzer.
RESULTS
We demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1β levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the overall generation of intracellular ATP. Upon MSU stimulation, CD11b-deficient macrophages showed an exacerbated secretion of IL-1β. Treating wild-type macrophages with a CD11b agonist, LA1, inhibited MSU-induced release of IL-1β in vitro and attenuated the severity of experimental gouty arthritis. Importantly, LA1, was also effective in human cells as it inhibited MSU-induced release of IL-1β by peripheral blood mononuclear cells from healthy donors.
CONCLUSION
Our data identified the CD11b integrin as a principal cell membrane receptor that modulates NLRP3 inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Macrophages; CD11b Antigen; Inflammasomes; Mice, Knockout; Uric Acid; Arthritis, Gouty; Mice; Mice, Inbred C57BL; Male
PubMed: 38863059
DOI: 10.1186/s13075-024-03350-5 -
International Journal of Exercise... 2024This study investigated the effects of biset, drop-set and traditional resistance training (RT) techniques on metabolic responses in resistance-trained males. Fifteen...
This study investigated the effects of biset, drop-set and traditional resistance training (RT) techniques on metabolic responses in resistance-trained males. Fifteen trained males (age 29.7 ± 6.1 years; body mass 83.4 ± 7.6 kg; RT experience 11.4 ± 6.7 years; one-repetition maximum (1RM) barbell bench press: body mass ratio 1.4 ± 0.1 a.u.) were assigned to three experimental conditions, in a randomized crossover design. The experimental conditions were bi-set (3×10 repetitions at 70%1RM in barbell bench press followed by 10 repetitions at 60%1RM in incline bench press), drop-set (3×10 repetitions at 70%1RM followed by 10 repetitions at 50%1RM in barbell bench press) and traditional RT (3×20 at 60%1RM in barbell bench press). A portable gas analyzer was used to assess energy expenditure and maximal oxygen uptake during the experimental protocols. Blood lactate levels were assessed at baseline and 1, 3, and 5 minutes after the training session. There were no differences for total training volume ( = 0.999). Post hoc comparisons revealed that bi-set elicited higher aerobic energy expenditure ( = 0.003 vs. drop-set; < 0.001 vs. traditional RT) and aerobic oxygen consumption ( = 0.034 vs. drop-set; < 0.001 vs. traditional RT) than other RT schemes. There were no differences regarding anaerobic EE between-conditions ( > 0.05). There was a main effect of time and condition for blood lactate levels ( < 0.001). Post hoc comparisons revealed that drop-set training elicited higher blood lactate levels than traditional RT ( = 0.009). The results suggest that RT techniques may have a potential role in optimizing metabolic responses in resistance-trained males.
PubMed: 38860033
DOI: No ID Found -
Scientific Reports Jun 2024Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis...
Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.
Topics: Humans; Scleroderma, Systemic; Female; Hypertension, Pulmonary; Middle Aged; Male; Aged; Retrospective Studies; Exercise Test; Exercise; Exercise Tolerance; Echocardiography; Oxygen Consumption; Cardiac Catheterization; Practice Guidelines as Topic; Vascular Resistance
PubMed: 38858443
DOI: 10.1038/s41598-024-63823-0 -
Cellular Physiology and Biochemistry :... Jun 2024Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among...
BACKGROUND/AIMS
Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session.
METHODS
We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation.
RESULTS
The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment.
CONCLUSION
Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole.
Topics: Animals; Male; Hypoxia; Rats; Rats, Wistar; Arginine; Oxygen Consumption; Oxidative Stress; Nitric Oxide; Oxygen; Adaptation, Physiological; Mitochondria, Liver; Oxidative Phosphorylation; Liver; Mitochondria, Heart; Lipid Peroxidation; Nitrites
PubMed: 38857359
DOI: 10.33594/000000705 -
SAGE Open Medicine 2024Functional electrical stimulation is important for the rehabilitation of patients with chronic heart failure. This meta-analysis of randomized controlled trials compared... (Review)
Review
The effect of functional electrical stimulation of the legs on cardiopulmonary function and quality of life in patients with chronic heart failure: A systematic review and meta-analysis.
INTRODUCTION
Functional electrical stimulation is important for the rehabilitation of patients with chronic heart failure. This meta-analysis of randomized controlled trials compared the efficacy of functional electrical stimulation versus conventional exercise training or placebo in patients with chronic heart failure.
METHODS
Studies were searched through PubMed, Embase, and the Cochrane Library databases up to 1 November 2023. The outcomes were cardiopulmonary function index (6-minute walking distance), peak oxygen consumption, and Minnesota Heart Failure Life Questionnaire quality of life scores. A subgroup analysis was conducted according to the ejection fraction. The 95% confidence interval and mean difference represented the outcome of the effect size.
RESULTS
Seventeen studies involving 732 participants were included. Compared with the control, functional electrical stimulation significantly improved peak oxygen consumption (MD = 2.84 ml/kg/min, 95% Cl: 1.99-3.68 ml/kg/min), increased 6-minute walking distance (MD = 49.52 m, 95% Cl: 22.61-76.43 m), and improved the life quality scores (MD = -12.86, 95% Cl: -17.48 to -7.88). Compared with functional electrical stimulation, exercise training also improved peak oxygen consumption (MD = -0.94 ml/kg/min, 95% Cl: -1.36 to -0.52 ml/kg/min), and the quality of life (QoL, MD = 0.66, 95% Cl: 0.34-0.98, < 0.05, = 38%), but the result of 6-minute walking distance (MD = -6.97 m, 95% Cl: -18.32 to -4.38 m) did not show a difference. Further subgroup analysis showed that outcomes including the above, significantly improved under the functional electrical stimulationfor both HF patients with reduced ejection fraction and HF patients with preserved ejection fraction patients, but difference is insignificant of the results between groups of aerobic exercise and functional electrical stimulationacted on patients with HF patients with reduced ejection fraction.
CONCLUSIONS
Our study demonstrates that compared with placebo, functional electrical stimulation benefits the patients with chronic heart failure on cardiopulmonary function and quality of life. Furthermore, HF patients with reduced ejection fraction patients benefit more from functional electrical stimulation than HF patients with reduced ejection fraction patients. Therefore, functional electrical stimulation is a promising complementary therapy for patients with chronic heart failure.
PubMed: 38855004
DOI: 10.1177/20503121241245003 -
RSC Advances Jun 2024The rational design and facile preparation of a catalyst with high activity, strong durability and low consumption for the oxygen evolution reaction (OER) is an ongoing...
The rational design and facile preparation of a catalyst with high activity, strong durability and low consumption for the oxygen evolution reaction (OER) is an ongoing challenge in water splitting to generate clean and renewable H fuel. Herein, bimetallic metal-organic frameworks (MOFs) with a uniform morphology, controlled metal ratio and low crystallinity were constructed using a simple and reliable one-step solvothermal method. The three-dimensional (3D) flower-like MOF (F-Ni1Co4-BTC) with a Ni to Co molar ratio of 1 : 4 coordinated with 1,3,5-benzenetricarboxylic acid exhibited excellent OER catalytic activity compared with its corresponding counterparts, which can be attributed to the establishment of the exquisite morphology, the proportion of the dual-metal center, and the formation of active intermediates. Furthermore, when F-Ni1Co4-BTC was directly grown on carbon cloth (F-Ni1Co4-BTC/CC), it achieved an obvious improvement in electrochemical performance, affording a low overpotential of 292 mV at a current density of 10 mA cm, a small Tafel slope (48 mV dec), and excellent mechanical durability in an alkaline electrolyte, which is due to the integrated electrode attained richer active sites and faster electron transfer rate with the introduction of highly conductive carbon cloth. Our work offers a promising strategy to tailor the properties of bimetallic MOFs and the possibility of highly efficient earth-abundant catalysts for practical applications.
PubMed: 38854837
DOI: 10.1039/d4ra02280g -
Animal Models and Experimental Medicine Jun 2024This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health, elucidating the underlying mechanisms involving the... (Review)
Review
This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health, elucidating the underlying mechanisms involving the Toll-like receptor 4 (TLR4)/Nuclear factor kappa light chain enhancer of activated B cells (NF-kB) pathway and the Cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. The TLR4/NF-kB pathway, crucial for inflammatory and immune responses, triggers the production of pro-inflammatory agents and type-1 interferon, disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to alcohol. Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns (PAMPs), leading to liver cell infection and subsequent inflammation. Concurrently, CYP2E1-mediated alcohol metabolism generates ROS, causing oxidative stress and damaging cells, lipids, proteins, and deoxyribonucleic acid (DNA). To counteract this inflammatory imbalance, Nrf2 regulates gene expression, inhibiting inflammatory progression and promoting antioxidant responses. Excessive alcohol intake results in elevated liver enzymes (ADH, CYP2E1, and catalase), ROS, NADH, acetaldehyde, and acetate, leading to damage in vital organs such as the heart, brain, and lungs. Moreover, alcohol negatively affects reproductive health by inhibiting the hypothalamic-pituitary-gonadal axis, causing infertility in both men and women. These findings underscore the profound health concerns associated with alcohol-induced damage, emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ impacts of alcohol consumption.
PubMed: 38853347
DOI: 10.1002/ame2.12436