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Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： Matheus Truccolo Michalczuk Larisse Longo Melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari JoséEduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-*** with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease Rifaximin

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Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study

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World Journal of Transplantation 2024年第1期14卷 130-140页

作者： Geisiane Custodio Andrew Maykon Massutti Aline Caramori Taynara Gonçalves Pereira Augusto Dalazen Gabriela Scheidt Ludmilla Thomazini Cristiane Bauermann Leitão Tatiana Helena Rech Department of Intensive Care Unit Hospital Santa IsabelBlumenau-Santa Catarina CEP-89010906Brazil Transplant Division Hospital Santa IsabelBlumenau-Santa Catarina CEP-89010906Brazil school of Medicine Universidade Regional de Blumenau(FURB)Blumenau-Santa Catarina CEP-89010906Brazil school of Medicine Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Brazil Departement of Endocrinology Hospital de Clínicas de Porto Alegre/Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Department of Internal Medicine Hospital de Clínicas de Porto AlegreDivision of Intensive Care MedicinePorto Alegre 90035-903Brazil

BACKGROUND Prolonged donor hepatectomy time may be implicated in early and late complications of liver *** To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients,mainly early allograft *** This multicenter retrospective study included brain-dead donors and adult liver graft ***-recipient matching was obtained through a crossover *** and laboratory data were recorded for both donors and *** hepatectomy,cold ischemia,and warm ischemia times were *** outcome was early allograft *** outcomes included need for retransplantation,length of intensive care unit and hospital stay,and patient and graft survival at 12 *** From January 2019 to December 2021,a total of 243 patients underwent a liver transplant from a brain-dead *** these,57(25%)developed early allograft *** median donor hepatectomy time was 29(23–40)*** with early allograft dysfunction had a median hepatectomy time of 25(22–38)min,whereas those without it had a median time of 30(24–40)min(P=0.126).CONCLUSION Donor hepatectomy time was not associated with early allograft dysfunction,graft survival,or patient survival following liver transplantation.

关键词： Brain death Hepatectomy Liver transplantation Early allograft dysfunction Graft survival

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Metabolic disease and the liver: A review

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World Journal of Hepatology 2024年第1期16卷 33-40页

作者： Márcia Vargas Sheila de Castro Cardoso Toniasso Patricia G Riedel Camila Pereira Baldin Francielle Lopes dos Reis Robson Martins Pereira Maria Carlota Borba Brum Dvora Joveleviths Mario Reis Alvares-da-Silva Program of Graduate Science in Gastroenterology and Hepatology Federal University of Rio Grande do SulPorto Alegre 90040-060Rio Grande do SulBrazil school of Medicine Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Program of Graduate Science in Gastroenterology and Hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90410000Brazil Medicine Faculty Federal University of rio grande do Sul Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Division of Gastroenterology and Hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90035007Brazil

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin *** presence of metabolic comorbidities coexisting with liver disease varies substantially among *** is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with *** steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of *** diagnosis is based on the presence of steatosis,noninvasive scores and altered liver *** scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely ***,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical ***,there is no definite pharmacological treatment for the *** public health policies to treat patients with risk factors for MASLD prevention is essential.

关键词： Nonalcoholic fatty liver disease Primary care Metabolic risk Liver Metabolism

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Neurogenic potential of NG2 in neurotrauma:a systematic review

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Neural Regeneration Research 2024年第12期19卷 2673-2683页

作者： Yuri R.Rigo Radharani Benvenutti Luis V.Portela Nathan R.Strogulski Departamento de Bioquímica Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do Sul(UFRGS)Porto AlegreBrazil school of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublinIreland school of Biochemistry and Immunology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of *** is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain *** advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma *** studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed *** these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from *** the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to ***,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in *** also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury *** findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.

关键词： neural-glial antigen 2 neural-glial factor 2 neuron differentiation NG2 cell regeneration spinal cord injury(SCI) traumatic brain injury(TBI)

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Study of hybrid nanofluid flow in a stationary cone-disk system with temperature-dependent fluid properties

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 677-694页

作者： A.S.JOHN B.MAHANTHESH G.LORENZINI Center for Mathematical Needs Department of MathematicsCHRIST(Deemed to be University)Karnataka 560029India school of Mathematical and Statistical Sciences The University of Texas Rio Grande ValleyTexas 78539U.S.A. Department of Engineering and Architecture University of ParmaParma 43124Italy

Cone-disk systems find frequent use such as conical diffusers,medical devices,various rheometric,and viscosimetry *** this study,we investigate the three-dimensional flow of a water-based Ag-Mg O hybrid nanofluid in a static cone-disk system while considering temperature-dependent fluid *** the variable fluid properties affect the dynamics and heat transfer features is studied by Reynolds's linearized model for variable viscosity and Chiam's model for variable thermal *** single-phase nanofluid model is utilized to describe convective heat transfer in hybrid nanofluids,incorporating the experimental *** model is developed as a coupled system of convective-diffusion equations,encompassing the conservation of momentum and the conservation of thermal energy,in conjunction with an incompressibility condition.A self-similar model is developed by the Lie-group scaling transformations,and the subsequent self-similar equations are then solved *** influence of variable fluid parameters on both swirling and non-swirling flow cases is ***,the Nusselt number for the disk surface is *** is found that an increase in the temperature-dependent viscosity parameter enhances heat transfer characteristics in the static cone-disk system,while the thermal conductivity parameter has the opposite effect.

关键词： hybrid nanofluid cone-disk system laminar flow variable fluid property Nusselt number

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Experimental evidence of pressure effects on spinel dissolution and peridotite serpentinization kinetics under shallow hydrothermal conditions

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Geoscience Frontiers 2024年第2期15卷 236-250页

作者： Yuri de Melo Portella Rommulo Vieira Conceição Tiago Abreu Siqueira Lucas Bonan Gomes Rodrigo Sebastian Iglesias Programa de Pós-Graduação em Geociências(PPGGEO) Universidade Federal do Rio Grande do SulPorto AlegreBrazil Petrobras–Petróleo Brasileiro S.A. Avenida Henrique Valadares 28CentroRio de Janeiro(RJ)20231-030Brazil Instituto do Petróleo e dos Recursos Naturais-PUCRS–Pontifícia universidade Católica do rio grande do Sul 90619-900Porto AlegreBrazil universidade Federal do rio grande do Sul Instituto de GeociênciasLaboratório de Difratometria de Raios XPorto AlegreBrazil Escola Politécnica–PUCRS-Pontifícia universidade Católica do rio grande do Sul 90619-900 Porto AlegreBrazil

Serpentinization reactions are paramount to understand hydro-geothermal activity near plate boundaries and mafic–ultramafic massifs,as well as fluid and element transfer between the Earth’s mantle and ***,fluid-rock element exchange and serpentinization kinetics under shallow hydrothermal conditions is still largely *** we present two constant temperature(230℃)time-series of natural peridotite(77.5%olivine;13.7%enstatite;6.8%diopside;2%spinel)serpentinization experiments:at 13.4 MPa;and 20.7 ***-enriched lizardite was the main secondary mineral in all runs after olivine(olv)and orthopyroxene(opx)serpentinization(without any detectable brucite,talc or magnetite),while primary spinel and diopside partially dissolved during the *** serpentinization stages comprises intrinsically coupled reactions between olivine and enstatite,as Al and Si are progressively transferred from orthopyroxene-derived to olivine-derived serpentine,while the opposite is true for Mg and Fe,with homogenization of serpentines compositions after 40 *** Ni/Cr ratios of serpentines,however,remain diagnostic of the respective primary *** average serpentine content indicates fast serpentinization rates of 0.55 wt.%·day^(-1)(0.26 mmol·day^(-1))and 0.26 wt.%·day^(-1)(0.13 mmol·day^(-1))at 13.4 and 20.7 MPa,*** 2x faster serpentinization kinetics at lower pressure is likely linked to enhanced spinel dissolution leading to one order of magnitude higher available Al,which accelerates olivine serpentinization while delays orthopyroxene ***,time-dependent increase in solid products masses suggests rock volume expands linearly 0.37%±0.01%per serpentine wt.%independently of *** balance constrains suggests olv:opx react at~5:2 and~3:2 M ratios,resulting in Si-deficient and Si-saturated serpentines at the end of the low-pressure series(13.4 MPa)and high-pressure series(20.7 MPa),***

关键词： Serpentine Volume expansion Serpentinization fluids Lost City hydrothermal field Serpentinite-hosted hydrothermal systems Hydrogen(H_(2))generation

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Analysis of Perinatal Outcomes of Twin Pregnancy in a Referral Hospital for High Risk

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Open Journal of Obstetrics and Gynecology 2024年第7期14卷 983-995页

作者： Eduarda Paim Pedro Lucas Carneiro Ferreira Luciano Selistre Fernanda Grossi José Mauro Madi Gabriela Françoes Rostirolla Mdica Residente do Programa de Residncia em Ginecologia e Obstetrcia Hospital Geral de Caxias do Sul Rio Grande do Sul Brasil Faculdade de Medicina Universidade de Caxias do Sul Rio Grande do Sul Brasil Programa de Ps-Graduao Universidade de Caxias do Sul Rio Grande do Sul Brasil Servio de Ginecologia e Obstetrcia Hospital Geral de Caxias do Sul Rio Grande do Sul Brasil

Introduction: The incidence of twin pregnancies has increased significantly in recent decades. These pregnancies require more attention due to their worse outcomes than singleton pregnancies. Objective: To analyze the characteristics and perinatal outcomes of twin pregnancies at the Caxias do Sul General Hospital. Methods: This is a descriptive and retrospective study that included all births related to twin pregnancies between March 1998 and June 2018. Maternal and perinatal variables were analyzed. Descriptive analyses were carried out using measures of central tendency and dispersion for continuous variables (mean and standard deviation or median and interquartile range), according to a prior assessment of distribution using the Shapiro-Wilk test, and absolute (n) and relative (n%) frequencies for categorical variables. Results: 172 pairs of twins/21,972 births (0.8%) were identified. There was a high percentage of interpartum interval of less than 12 months, adherence and prenatal visits, body mass index, and need for neonatal intensive care. Stillbirth and neomortality rates were within acceptable parameters. Conclusion: The sample studied showed a percentage similar to that in the literature, a high rate of maternal and perinatal complications, characterizing it as a high-risk fetal pregnancy.

关键词： Pregnancy Twin Pregnancy High Risk Pregnancy Morbidity Perinatal Mortality Perinatal Results

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Evaluation of the Antibacterial and Antifungal Capacity of Nanoemulsions Loaded with Synthetic Chalcone Derivatives Di-Benzyl Cinnamaldehyde and Benzyl 4-Aminochalcone

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Journal of Renewable Materials 2024年第2期12卷 285-304页

作者： Flavia Oliveira Monteiro da Silva Abreu Taysse Holanda Joice Farias do Nascimento Henety Nascimento Pinheiro Rachel Menezes Castelo Hélcio Silva dos Santos Thais Benincá Patrícia da Silva Malheiros Júlio César Sousa Prado Raquel de Oliveira Fontenelle Maria Madalena de Camargo Forte Natural Polymers Laboratory PPGCNState University of CearáFortaleza60.714.903Brazil Polymeric Materials Laboratory PPGE3MFederal University of Rio Grande do SulPorto Alegre91501-970Brazil Natural Product Chemistry Laboratory PPGCNState University of CearáFortaleza60.714.903Brazil Food Hygiene and Microbiology Laboratory PPGCTAFederal University of Rio Grande do SulPorto Alegre91501-970Brazil Microbiology Laboratory Medicine SchoolFederal University of CearáSobral62010-560Brazil

With the increase in antimicrobial resistance,it has become necessary to explore alternative approaches for combating and preventing ***-cinnamaldehyde(CNM)and Benzyl4-amino(B4AM)are bioactive compounds derived from chalcones but with restricted solubility in aqueous *** can enhance the solubility of compounds and can be a promising alternative in the development of novel antimicrobials,with reduced side effects and prolonged *** objective of this study was to evaluate the stability of oil-in-water nanoemulsions loaded with two distinct types of chalcones at two different dosages,to propose a stable formulation with antimicrobial *** showed that nanoemulsions presented high encapsulation efficiency,low polydispersity index(PDI)and particle size below 200 nm,indicating that emulsification was a suitable method for nanoemulsion *** with higher dosages exhibited significant antimicrobial effects when compared to free chalcones and positive ***,B4AM nanoemulsions at higher dosages showed expressive activity against Salmonella minnesota,with a 420%greater inhibitory response compared to the free form and showing equivalence to the positive *** nanoemulsions showed excellent inhibitory activity at the highest dosage,equivalent to the positive control against *** and Staphylococcus *** greater number of conjugated bonds in CNM increased the antimicrobial activity in comparison with B4AM,and the formation of nanometric domains enhanced the bioavailability,being a promising alternative for antimicrobial applications.

关键词： Polysaccharide nanoemulsions S.aureus S.minnesota chalcones alginate

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Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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World Journal of Hepatology 2024年第5期16卷 832-842页

作者： Elisa Carolina Lange Pabulo Henrique Rampelotto Larisse Longo Laura Bainy Rodrigues de Freitas Carolina Uribe-Cruz Mario Reis Alvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Bioinformatics and Biostatistics Core Facility Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Brazil Graduate Program in Biological Sciences:Pharmacology and Therapeutics Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007RSBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)researcher Brasília 71605-001Brazil

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic *** suggest ornithine aspartate(LOLA)as drug *** To analyze the influence of LOLA intake on gut microbiota using a nutritional model of *** Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were *** fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™*** Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides *** functional prediction provided two different metabolic profiles between MASLD and *** 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides *** 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA *** Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

关键词： Animal model Gut microbiota Metabolic-associated steatotic liver disease Metabolic prediction Ornithine aspartate

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Exercise training mode effects on myokine expression in healthy adults:A systematic review with meta-analysis

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Journal of Sport and Health Science 2024年第6期13卷 764-779页

作者： Francesco Bettariga Dennis R.Taaffe Daniel A.Galvao Pedro Lopez Chris Bishop Anna Maria Markarian Valentina Natalucci Jin-Soo Kim Robert U.Newton Exercise Medicine Research Institute Edith Cowan UniversityJoondalupWA 6027Australia school of medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia Pleural Medicine Unit Institute for Respiratory HealthPerthWA 6009Australia medical school Faculty of Health&Medical SciencesUniversity of Western AustraliaPerthWA 6009Australia Grupo de Pesquisa em Exercıcio para Populacoes Clınicas(GPCLIN) Universidade de Caxias do SulCaxias do SulRio Grande do Sul 95070-560Brazil London Sport Institute School of Science and TechnologyMiddlesex UniversityLondonNW44BTUK Department of Pathophysiology and Transplantation University of MilanMilan 20133Italy school of Human Movement and Nutrition Sciences University of QueenslandSt.LuciaQLD 4072Australia

Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully *** muscle secretes myokines,which mediate muscleorgan *** regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer *** date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be *** is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical ***:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April *** studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of ***:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically *** aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across *** levels returned to baseline levels within 180 min to 24 h ***,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be ***:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic *** research is required to investigate the effects of different exercise modes at multiple time points on myok

关键词： Myokine Resistance exercise Aerobic exercise Cytokine Systemic circulation

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