Treinamento de força associado a suplementação de creatina na manutenção da massa livre de gordura em idosos : uma revisão sistemática e metanálise

Orientador: Dr. Tácito P. de Souza JuniorCoorientador: Dr. Ragami C. AlvesDissertação (mestrado) - Universidade Federal do Paraná, Setor de CIências Biológicas, Programa de Pós-Graduação em Educação Física. Defesa : Curitiba, 24/08/2022Inclui referênciasÁrea de concentração: Atividade física e saúde (Ciências do Movimento Humano)Resumo: Durante o processo de envelhecimento o corpo passa por mudanças e uma das principais e mais visível é a redução da massa livre de gordura, com isso pode ocorrer a redução da funcionalidade do idoso. O treino de força (TF) demonstra melhorar a composição corporal, em especial a massa muscular, e a creatina (Cr) poderia potencializar seu efeito. O objetivo da presente pesquisa foi verificar nas bases de dados o efeito de um programa de TF associado a suplementação de creatina na melhora da massa muscular em indivíduos idosos. Foi pesquisado nas bases de dados PUBMED, Web of Science, Scopus e Bireme por artigos randomizados e duplo-cego que utilizaram o TF associado a suplementação de Cr em idosos. Foram incluídos estudos que apresentaram a ação da suplementação de creatina em conjunto ao treinamento de força conduzidos em idosos (? 60 anos), que avaliaram massa livre de gordura pré e pós intervenção, nos quais um grupo intervenção é comparado a um grupo controle e/ou placebo. Foi encontrado um total de 575 artigos, após a aplicar primeira seleção sobraram 31 artigos para a leitura, aplicando os critérios de inclusão foram selecionados 6 artigos. Em conclusão, o TF + Cr não demonstrou aprimorar a resposta para ganho de massa livre de gordura. Os resultados desta meta-análise não verificaram efeito significativo da suplementação para a melhora massa livre de gordura, que poderá influenciar no envelhecimento saudável.Abstract: During the aging process, the body undergoes changes and one of the main and most visible changes is the reduction in fat-free mass, which can lead to a reduction in the functionality of the elderly. Strength training (ST) has been shown to improve body composition, especially muscle mass, and creatine (Cr) could enhance its effect. The objective of this research was to verify in the databases the effect of a ST program associated with creatine supplementation in the improvement of muscle mass in elderly individuals. The PUBMED, Web of Science, Scopus and Bireme databases were searched for randomized and double-blind articles that used TF associated with Cr supplementation in the elderly. Studies were included that demonstrated the action of creatine supplementation in conjunction with sustained strength training in the elderly (? 60 years), which evaluated pre- and post-intervention fat free mass, in which an intervention group is against a control group and/or placebo. A total of 575 articles were found, after applying the first selection, 31 articles remained for reading, applying the inclusion criteria, 6 articles were selected. TF + Cr did not improve the response to fat-free mass gain. The results of this meta-analysis did not verify a significant effect of supplementation to improve fat-free mass, which could influence healthy aging

Consequências da rápida redução de peso corporal em atletas de esportes de combate e a importância da nutrição: uma revisão

Os esportes de combate geralmente são divididos por categorias de peso. Com o intuito de obter vantagem lutando com adversários mais leves e fracos, muitos atletas costumam reduzir seu peso corporal de forma rápida através de estratégias potencialmente perigosas à saúde. O objetivo dessa revisão foi sistematizar os principais achados da literatura a respeito das consequências da prática de redução rápida de peso sobre os sistemas fisiológicos e desempenho, bem como verificar a importância da nutrição nesse contexto. A revisão de literatura englobou publicações nacionais e internacionais, com datas compreendidas entre janeiro de 1970 e maio de 2017, nas bases de dados eletrônicas: Elsevier, Medline, Pubmed, Scopus, Sportdiscus e Web of Science. As palavras chaves utilizadas na busca estavam incluídas na Thesaurus Medical Subject Headings (MeSH) desenvolvido pela U.S. National Library of Medicine. A literatura científica se mostrou unânime em demonstrar os efeitos sobre os sistemas fisiológicos, como: redução da densidade óssea; aumento do desenvolvimento de transtornos alimentares; depressão do sistema imune; disfunções do sistema cardiovascular e hipertermia. Quanto ao desempenho, há consenso na literatura de que a rápida redução de peso diminui o desempenho aeróbio. No entanto, os efeitos sobre o desempenho anaeróbio ainda são divergentes, pois dependem do período existente entre a pesagem e os combates. Diversos estudos mostraram que os hábitos alimentares afetam decisivamente a saúde, o peso, a composição corporal e o desempenho esportivo, sendo as intervenções nutricionais eficazes na redução de peso de forma gradual através da redução da quantidade calórica total. ABSTRACT Consequences of body weight rapid reduction in athletes of combat sports and the importance of nutrition: a reviewThe combat sports are usually divided by weight categories. In order to gain an advantage by struggling with lighter and weaker opponents, many athletes often reduce their body weight quickly through potentially dangerous strategies. The objective of this review was to systematize the main findings of the literature regarding the consequences of the practice of rapid weight reduction on physiological systems and performance, as well as to verify the importance of nutrition in this context. The literature review included national and international publications, with dates between January 1970 and May 2017, in the electronic databases: Elsevier, Medline, Pubmed, Scopus, Sportdiscus and Web of Science. Key words used in the search were included in the Thesaurus Medical Subject Headings (MeSH) developed by the U.S. National Library of Medicine. The scientific literature was unanimous in demonstrating the effects on the physiological systems, such as: reduction of bone density; Increased development of eating disorders; Depression of the immune system; Dysfunctions of the cardiovascular system and hyperthermia. Regarding performance, there is consensus in the literature that rapid weight reduction decreases aerobic performance. However, the effects on anaerobic performance are still divergent as they depend on the time between weighing and fighting. Several studies have shown that eating habits decisively affect health, weight, body composition and sports performance, and nutritional interventions are effective in reducing weight gradually by reducing total caloric intake

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility