Transcriptional Profiling of SARS-CoV-2-Infected Calu-3 Cells Reveals Immune-Related Signaling Pathways.

The COVID-19 disease, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in late 2019 and rapidly spread worldwide, becoming a pandemic that infected millions of people and caused significant deaths. COVID-19 continues to be a major threat, and there is a need to deepen our understanding of the virus and its mechanisms of infection. To study the cellular responses to SARS-CoV-2 infection, we performed an RNA sequencing of infected vs. uninfected Calu-3 cells. Total RNA was extracted from infected (0.5 MOI) and control Calu-3 cells and converted to cDNA. Sequencing was performed, and the obtained reads were quality-analyzed and pre-processed. Differential expression was assessed with the EdgeR package, and functional enrichment was performed in EnrichR for Gene Ontology, KEGG pathways, and WikiPathways. A total of 1040 differentially expressed genes were found in infected vs. uninfected Calu-3 cells, of which 695 were up-regulated and 345 were down-regulated. Functional enrichment analyses revealed the predominant up-regulation of genes related to innate immune response, response to virus, inflammation, cell proliferation, and apoptosis. These transcriptional changes following SARS-CoV-2 infection may reflect a cellular response to the infection and help to elucidate COVID-19 pathogenesis, in addition to revealing potential biomarkers and drug targets.

Supraphysiological doses of nandrolone decanoate disrupts spermatogenesis but did not interfere on embryo rate.

The aim of this study was to investigate the effects of 10 mg/kg/week of nandrolone decanoate (DECA - Deca Durabolin®) on body composition, hormonal levels, spermatic parameters, redox status, and morphometric parameters of testicle and epididymis; furthermore, the fertility capacity of Wistar rats was measured thought in vitro fertilization (IVF). The animals (n = 16) were divided into two groups: control group (CTRL, n = 8), which received only vehicle composed by peanut oil and 10% of the benzoic alcohol and nandrolone decanoate group (DECA, n = 8), which received intramuscular injections of DECA for 8 weeks, both groups were treated for 8 weeks. The results demonstrate significative decrease in visceral fat, testosterone levels, and thiol content on epididymis, reduction on normal sperm parameters, and deleterious effect on testicles and epididymis tissue morphology showing reduction of germ height and luminal diameter on the DECA group. Thus, it can be concluded that high doses of nandrolone decanoate impairs male reproductive parameters.

Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights.

PURPOSE: Dipeptidyl peptidase 4 (DPP4) inactivates a range of bioactive peptides. The cleavage of insulinotropic peptides and glucagon-like peptide 1 (GLP1) by DPP4 directly influences glucose homeostasis. This study aimed to describe the mode of interaction between sitagliptin (an antidiabetic drug) and human DPP4 using in silico approaches. MATERIALS AND METHODS: Docking studies were conducted using AutoDock Vina, 2D and 3D schematic drawings were obtained using PoseView and PLIP servers, and the DPP4-sitagliptin complex was visualized with Pymol software. RESULTS: The best affinity energy to form the DPP4-sitagliptin complex was E-value â€‹= â€‹- 8.1 â€‹kcal â€‹mol-1, as indicated by docking simulations. This result suggests a strong interaction. According to our observations, hydrophobic interactions involving the amino acids residues Tyr663 and Val712, hydrogen bonds (Glu203, Glu204, Tyr663, and Tyr667), π-Stacking interactions (Phe355 and Tyr667), and halogenic bonds (Arg123, Glu204, and Arg356) were prevalent in the DPP4-sitagliptin complex. Root Mean Square Deviation prediction also demonstrated that the global structure of the human DPP4 did not have a significant change in its topology, even after the formation of the DPP4-sitagliptin complex. CONCLUSION: The stable interaction between the sitagliptin ligand and the DPP4 enzyme was demonstrated through molecular docking simulations. The findings presented in this work enhance the understanding of the physicochemical properties of the sitagliptin interaction site, supporting the design of more efficient gliptin-like iDPP4 inhibitors.

Regional phase angle, not whole-body, is augmented in response to pre-season in professional soccer players.

The objective of this article was to assess the effects of six-week pre-season training on whole-body and regional bioelectrical impedance analysis (BIA)-derived parameters, body composition, power, and aerobic performance in professional soccer players. Ten professional soccer athletes participated in the present study. Whole-body and regional hamstrings BIA-derived parameters [resistance, reactance, impedance, phase angle (PhA)], body composition, total body water (TBW), intracellular (ICW), and extracellular (ECW) were measured before, at mid-point, and after sixth week of the pre-season. Power (countermovement jump and squat jump) and aerobic capacity (Yo-Yo test) were measured before and after pre-season. There was a significant increase in the regional PhA (+13.9%) but not in the whole-body. There was a reduction in fat mass (-4.1%), an increase in fat-free mass (+1.7%), TBW (+8.3%), ICW (+8.8%), and ECW (+7.6%), as well as an increase in jump height (+11.0%) and distance covered in the Yo-Yo test (+34.7%). From our results, it is possible to suggest that pre-season training can induce an increase in hamstring PhA as well as body recomposition and improvement of physical fitness in professional soccer players.

High-Intense Interval Training Prevents Cognitive Impairment And Increases The Expression Of Muscle Genes Fndc5 And Ppargc1a In A Rat Model Of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease is the most common neurodegenerative disease in the world, characterized by the progressive loss of neuronal structure and function, whose main histopathological landmark is the accumulation of ß-amyloid in the brain. OBJECTIVE: It is well known that exercise is a neuroprotective factor and that muscles produce and release myokines that exert endocrine effects in inflammation and metabolic dysfunction. Thus, this work intends to establish the relationship between the benefits of exercise through the chronic training of HIIT on cognitive damage induced by the Alzheimer's model by the injection of ß amyloid 1-42. METHODS: For this purpose, forty-eight male Wistar rats were divided into four groups: Sedentary Sham (SS), Trained Sham (ST), Sedentary Alzheimer's (AS), and Trained Alzheimer's (AT). Animals were submitted to stereotactic surgery and received a hippocampal injection of Aß1-42 or a saline solution. Seven days after surgery, twelve days of treadmill adaptation followed by five maximal running tests (MRT) and fifty-five days of HIIT, rats underwent the Morris water maze test. The animals were then euthanized, and their gastrocnemius muscle tissue was extracted to analyze the Fibronectin type III domain containing 5 (FNDC5), PPARG Coactivator 1 Alpha (PPARGC1A), and Integrin subunit beta 5 (ITGB5-R) expression by qRT-PCR in addition to cross-sectional areas. RESULTS: The HIIT prevents the cognitive deficit induced by the infusion of amyloid ß 1-42 (p<0.0001), causes adaptation of muscle fibers (p<0.0001), modulates the gene expression of FNDC5 (p<0.01), ITGB5 (p<0.01) and PPARGC1A (p<0.01), and induces an increase in peripheral protein expression of FNDC5 (p<0.005). CONCLUSION: Thus, we conclude that HIIT can prevent cognitive damage induced by the infusion of Aß1-42, constituting a non-pharmacological tool that modulates important genetic and protein pathways.

Serum and Urinary Neutrophil Gelatinase-Associated Lipocalin Are Not Associated With Serum Redox Parameters in Amateur Athletes After an Ultramarathon.

Objective: To evaluate the relationship between oxidative stress and NGAL levels in blood and urine of amateur athletes after participating in a 100 km ultramarathon. Methodology: The sample was composed of seven athletes, submitted to anthropometric assessment, cardiopulmonary exercise test, collection of urine and blood, measurement of body weight. The rate of perceived exertion (RPE), competition duration, heart rate (HR), energy expenditure and oxygen consumption (V'O2") were also measured during the event. The energy consumption during the race was verified at its end. The analyses were based on the means (M) and respective standard deviations (SD), with statistical significance set at 5% (p < 0.05). Paired t-test was used for comparison between the periods before and after the competition, and Pearson's correlation coefficient was used to measure the linear correlation between quantitative variables. Results: Body mass index (BMI) of the sample was 25.75 kg/m2 ± 3.20, body fat percentage 18.54% ± 4.35% and V'O2"max 48.87% ± 4.78. Glucose, cortisol, and neutrophil gelatinase-associated lipocalin (NGAL) (p < 0.01) as well as glutathione peroxidase (GPx) active were higher after the race when compared to basal values. Moreover, lactate, creatinine, microalbuminuria, and glomerular filtration rate (GFR) (p < 0.001) were also higher after the race. After the competition, there was a significant correlation only between serum NGAL and creatinine, which was classified as strong and positive (r: 0.77; p < 0.05). There was a significant reduction (p < 0.05) of body weight after the event (72.40 kg ± 9.78) compared to before it (73.98 kg ± 10.25). In addition, we found an increase of RPE (p < 0.001) after the race. The competition lasted 820.60 min (±117.00), with a 127.85 bpm (±12.02) HR, a 2209.72 kcal ± 951.97 energy consumption, 7837.16 kcal ± 195.71 energy expenditure, and 28.78 ml/kg/min-1 (±4.66) relative V'O2"max. Conclusion: The lack of correlation between oxidative stress biomarkers and serum and urine NGAL suggests that NGAL is more sensitive to inflammatory processes than to ROS levels.

Pulmonary impairment in type 2 diabetic rats and its improvement by exercise.

AIM: We aimed to evaluate whether the streptozotocin-induced diabetic model can generate lung functional, histological and biochemical impairments and whether moderate exercise can prevent these changes. METHODS: Wistar rats were assigned to control (CTRL), exercise (EXE), diabetic (D) and diabetic with exercise (D+EXE) groups. We used the n5-STZ model of diabetes mellitus triggered by a single injection of streptozotocin (STZ, 120 mg/kg b.w., i.p.) in newborn rats on their 5th day of life. EXE and D+EXE rats were trained by running on a motorized treadmill, 5 days a week for 9 weeks. Blood glucose, body weight, food intake, exercise capacity, lung mechanics, morphology, and antioxidant enzymatic activity were analysed. RESULTS: On the 14th week of life, diabetic rats exhibited a significant impairment in post-prandial glycaemia, glucose tolerance, body weight, food intake, lung function (tissue viscance, elastance, Newtonian resistance and hysteresis), morphological parameters, redox balance and exercise capacity. Physical training completely prevented the diabetes-induced alterations, except for those on fasting blood glucose, which nevertheless remained stable. CONCLUSIONS: Mild diabetes in n5-STZ-treated rats jeopardized pulmonary mechanics, morphology and redox balance, which confirms the occurrence of diabetes-induced pneumopathy. Moreover, moderate exercise completely prevented all diabetes-induced respiratory alterations.

Effect of involuntary chronic physical exercise on beta-amyloid protein in experimental models of Alzheimer's disease: Systematic review and meta-analysis.

The excessive deposition of ß-amyloid proteins (Aß) is directly correlated with the establishment and development of Alzheimer's Disease (AD). Current treatments for AD only reduce symptoms instead of acting on Aß, the primary etiological agent. Hence, the anti-amyloid effect of regular exercise has been widely investigated as an alternative therapy. This systematic review and meta-analysis examined the anti-amyloid effect of regular physical exercise in animal models of AD. The search was conducted on the electronic databases Pubmed, Embase, Scopus and Web of Science without data limitation and using the following describers: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated using the SYRCLE's tool. Meta-analyses were conducted using models of random continuous effects. A total of 36 studies were selected and most used: transgenic mice (n = 29), treadmill training, duration of 12 weeks (interval of 4 to 28 weeks), rate of 60 min/day (interval of 30 min and up until free access) and speed of 12 m/min (interval of 3.2 to 32 m/min). The hippocampus and cortex were the most frequently investigated regions. Meta-analysis demonstrated a decrease in Aß with greater effect in unspecified isoforms Meta-analysis demonstrated a decrease in Aß with greater effect in unspecified isoforms (N = 4; SMD = -2.71, IC 95%: -3.59, -1.84, p < 0.00001, Q2 = 3.38, I2 = 11%) and Aß1-42 (N = 21; SMD = -1.94, IC 95%: -2.37, -1.51, p < 0.00001, Q2 = 33,37, I2 = 40%). Concerning training, greater effect was found with: 1) swimming (N = 4; SMD = -1.98, IC 95%: -3,28 - -0,68, p = 0.003, Q2 = 9.74, I2 = 69%), 2) moderate intensity (N = 4; SMD = -2.03, IC 95%: -3.31 - -0.75, p < 0.005, Q2 = 12.68, I2 = 76%); 3) duration up to six weeks (N = 6; N = 6; SMD = -2.35, IC 95%: -3.15 - -1.55, p < 0.00001, Q2 = 8.38, I2 = 40%); 4) young animals (SMD = -2.00, IC 95%: -2.59 - -1.42, p < 0.00001, Q2 = 24.90, I2 = 52%); 5) in the amygdala region (N = 1; SMD = -8.56, IC 95%: -12.88 - -4.23, p = 0.0001) and females (N = 4; SMD = -2.14, IC 95%: -3.48 - -0.79, p = 0.002, Q2 = 10.31, I2 = 71%). However, the reduction of Aß was associated with decrease of amyloidogenic pathway and increase of non-amyloidogenic. Hence, regular physical exercise demonstrated anti-amyloid effect in experimental models of AD through positive alterations in APP processing through different signaling pathways.

Transcriptional profile in rat muscle: down-regulation networks in acute strenuous exercise.

BACKGROUND: Physical exercise is a health promotion factor regulating gene expression and causing changes in phenotype, varying according to exercise type and intensity. Acute strenuous exercise in sedentary individuals appears to induce different transcriptional networks in response to stress caused by exercise. The objective of this research was to investigate the transcriptional profile of strenuous experimental exercise. METHODOLOGY: RNA-Seq was performed with Rattus norvegicus soleus muscle, submitted to strenuous physical exercise on a treadmill with an initial velocity of 0.5 km/h and increments of 0.2 km/h at every 3 min until animal exhaustion. Twenty four hours post-physical exercise, RNA-seq protocols were performed with coverage of 30 million reads per sample, 100 pb read length, paired-end, with a list of counts totaling 12816 genes. RESULTS: Eighty differentially expressed genes (61 down-regulated and 19 up-regulated) were obtained. Reactome and KEGG database searches revealed the most significant pathways, for down-regulated gene set, were: PI3K-Akt signaling pathway, RAF-MAP kinase, P2Y receptors and Signaling by Erbb2. Results suggest PI3K-AKT pathway inactivation by Hbegf, Fgf1 and Fgr3 receptor regulation, leading to inhibition of cell proliferation and increased apoptosis. Cell signaling transcription networks were found in transcriptome. Results suggest some metabolic pathways which indicate the conditioning situation of strenuous exercise induced genes encoding apoptotic and autophagy factors, indicating cellular stress. CONCLUSION: Down-regulated networks showed cell transduction and signaling pathways, with possible inhibition of cellular proliferation and cell degeneration. These findings reveal transitory and dynamic process in cell signaling transcription networks in skeletal muscle after acute strenuous exercise.

Neuroprotective mechanisms of chronic physical exercise via reduction of ß-amyloid protein in experimental models of Alzheimer's disease: A systematic review.

AIMS: Alzheimer's disease (AD) is the most common irreversible chronic neurodegenerative disease. It is characterized by the abnormal accumulation of ß-amyloid protein (Aß), which triggers homeostatic breakage in several physiological systems. However, the effect of chronic exercise on the formation of Aß as an alternative therapy has been investigated. This systematic review examines the antiamyloid effect of different types and intensities of exercise, seeking to elucidate its neuroprotective mechanisms. MAIN METHODS: The research was conducted in the electronic databases Pubmed, Embase, Scopus and Web of Science, using the following descriptors: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated through SYRCLE's Risk of Bias for experimental studies. KEY FINDINGS: 2268 articles were found, being 36 included in the study. A higher frequency of use of mice with genetic alterations was identified for the Alzheimer's disease (AD) model (n = 29). It was used as chronic training: treadmill running (n = 24), voluntary running wheel (n = 7), swimming (n = 4) and climbing (n = 2). The hippocampus and the cortex were the most investigated regions. However, physiological changes accompanied by the reduction of Aß and associated with AD progression were verified. It is concluded that exercise reduces the production of Aß in models of animals with AD. SIGNIFICANCE: Nevertheless, this effect contributes to the improvement of several physiological aspects related to Aß and that contribute to neurological impairment in AD.

Test-retest reliability of electrical impedance myography in hamstrings of healthy young men.

Several techniques are available to assess muscle tissue status, including electrical impedance myography (EIM). Despite being used in the assessment of neuromuscular status in injury and response to exercise, reliability data for hamstrings muscles are limited. Therefore, this study aimed to determine the test-retest reliability of EIM components on hamstrings. Twenty-one healthy males (25.3 ± 3.4 years; 173 ± 6.7 cm; and 79.7 ± 15.9 kg) volunteered for this study. Subjects completed two visits, separated by seven days to collect EIM components (resistance, reactance, impedance, and phase angle) in the longitudinal and transversal axis of hamstrings in both thighs, using a bioimpedance device and Ag/AgCL adhesive contact electrodes. The electrode arrangement was in the muscular belly, half the distance between origin and insertion of the hamstrings. Reliability was determined by the intraclass correlation coefficient (ICC), minimal detectable change (MDC), and Bland-Altman plots. We observed high to excellent reliability (ICC > 0.85) between all EIM components, except for reactance with MDC ranged from 2.0 to 10.8 and the mean bias in Bland-Altman plots ranged from -0.02 to 2.48 (95% limits of agreement from -9.98 to 11.20). From our findings, the hamstrings assessment using EIM technique is reliable to assess muscle tissue; therefore, it enables the evaluation of changes/adaptations in clinical and applied contexts.

Functional analysis of gait with insole use in diabetic female rats: a cross-sectional study / Análise funcional da marcha com uso de palmilhas em ratas diabéticas: um estudo transversal / Análisis funcional de la marcha con uso de plantillas en ratas diabéticas: un estudio transversal

ABSTRACT Introduction: Diabetes mellitus is a chronic disease that is characterized by causing damage to the peripheral nervous system, generating sensory and motor changes. Objective: This study aims at analyzing the impact of the use of different orthotic insoles on the gait of diabetic female rats. Methods: Twenty-six female Wistar rats were randomly divided into the Control and Diabetic groups. The mechanical sensitivity test was performed manually on the surface of the animals' hind paws using the von Frey test. The functional evaluation was carried out on an adapted platform where the animals were stimulated to walk in order to capture images of the ventral region for measurements of the right and left hind paws. After the images were collected they were processed using Kinovea software version 0.8.27 to assess: stride distance, time, speed and acceleration. Results: There was a reduction in the weight of the animals in the Diabetic Group (p = 0.0018), associated with hyperglycemia (p = <0.0001), and a decrease in mechanical sensitivity as compared to the Control Group (p = 0.0372). Gait analysis showed a reduction in stride speed (p = 0.0482) and acceleration (p = 0.0149), with the silicone orthosis in the Diabetic Group. Conclusions: The silicone orthosis demonstrated a reduction in stride speed and acceleration, without compromising the other variables in the diabetic rats. The other insoles showed no functional difference between groups. Even though the animals showed a change in sensitivity at the end of 28 days of DM induction, this time does not appear to have been able to develop extensive changes in the rats' gait function. Level of evidence II; Therapeutic studies - Investigating the Results of Treatment.

RESUMO Introdução: O diabetes mellitus é uma doença crônica que se caracteriza por causar danos no sistema nervoso periférico, gerando alterações sensitivas e motoras. Objetivos: O presente trabalho tem como objetivo analisar o impacto do uso de diferentes órteses do tipo palmilha sobre a marcha de ratas diabéticas. Métodos: Vinte e seis ratas Wistar foram divididas randomicamente nos grupos Controle e Diabético. O teste de sensibilidade mecânica foi realizado manualmente na superfície da pata traseira dos animais com o teste de von Frey. A avaliação funcional foi feita em plataforma adaptada, na qual as ratas foram estimuladas a deambular, a fim de captar imagens da região ventral para medições das patas traseiras direita e esquerda. Depois da coleta, as imagens foram processadas no software Kinovea versão 0.8.27 para avaliar distância, tempo, velocidade e aceleração de um passo. Resultados: Observou-se redução do peso dos animais no Grupo Diabético (p = 0,0018), associado à hiperglicemia (p = <0,0001) e diminuição da sensibilidade mecânica em comparação com o Grupo Controle (p = 0,0372). Na análise da marcha, verificou-se redução da velocidade (p = 0,0482) e aceleração de um passo (p = 0,0149) com a órtese de silicone no Grupo Diabético. Conclusões: A órtese de silicone demonstrou redução da velocidade e da aceleração do passo, sem comprometimento das demais variáveis nas ratas diabéticas. As demais palmilhas não demonstraram diferença funcional entre os grupos. Ainda que os animais tenham apresentado alteração de sensibilidade, ao final de 28 dias de indução do DM, esse tempo parece não ter sido capaz de desenvolver alterações amplas na função da marcha das ratas. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: La diabetes mellitus es una enfermedad crónica que se caracteriza por causar daños al sistema nervioso periférico, generando alteraciones sensitivas y motoras. Objetivos: El presente trabajo tiene como objetivo analizar el impacto del uso de diferentes ortesis, del tipo plantilla sobre la marcha de ratas diabéticas. Métodos: Veintiséis ratas Wistar fueron divididas aleatoriamente en los grupos Control y Diabético. El test de sensibilidad mecánica fue realizado manualmente en la superficie de la pata trasera de los animales con el test de von Frey. La evaluación funcional fue hecha en plataforma adaptada, en la que se estimuló a las ratas a deambular, a fin de capturar imágenes de la región ventral para mediciones de las patas traseras derecha e izquierda. Después de la colecta, las imágenes se procesaron en el software Kinovea versión 0.8.27, para evaluar distancia, tiempo, velocidad y aceleración de un paso. Resultados: Se observó una reducción del peso de los animales en el Grupo Diabético (p = 0,0018), asociado a la hiperglucemia (p = <0,0001), y disminución en la sensibilidad mecánica en comparación con el Grupo Control (p = 0,0372). En el análisis de la marcha, se verificó reducción de la velocidad (p = 0,0482) y una aceleración de un paso (p = 0,0149), con la ortesis de silicona en el Grupo Diabético. Conclusiones: La ortesis de silicona demostró reducción de la velocidad y de la aceleración del paso, sin compromiso de las demás variables en las ratas diabéticas. Las demás plantillas no demostraron diferencia funcional entre los grupos. Aunque los animales hayan presentado alteración de la sensibilidad, al final de 28 días de inducción de DM, ese tiempo parece no haber sido capaz de desarrollar alteraciones amplias en la función de la marcha de las ratas. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Pesquisa translacional na era pós-genômica: avanços na área da transcriptômica / Translational research in the post-genomic era: advances in the field of transcriptomics

RESUMO A pesquisa translacional envolve a interface entre a pesquisa básica e a clínica médica com o intuito de gerar produtos ou processos inovadores para introduzi-los nos protocolos clínicos e nos sistemas de saúde. O objetivo desse ensaio foi apresentar uma visão geral dos avanços da transcriptômica, subsidiados pela disponibilidade e utilização das novas tecnologias da informação e biologia molecular. Na busca pelo diagnóstico preciso e menos invasivo, testes transcriptômicos utilizam assinaturas de expressão gênica visando detectar doenças neurodegenerativas (Parkinson e Alzheimer), autoimunes (lúpus eritematoso sistêmico, granulomatose de Wegener), insuficiência cardíaca, autismo e câncer (de mama, colorretal, hepático e de pulmão). No sistema de saúde inglês as diretrizes clínicas incorporam oito testes transcriptômicos, todos com foco no câncer. No Brasil testes genômicos com base nas sequências de DNA são regulamentados para diagnosticar anomalias congênitas, tanto no Sistema Único de Saúde, como na saúde suplementar, mas os testes moleculares não avançaram no âmbito da transcriptômica diagnóstica. O sistema de saúde brasileiro deveria ir além dos testes de análise genômica e iniciar o processo de regulamentação das tecnologias transcriptômicas de diagnóstico. No futuro, testes diagnósticos avaliando múltiplos perfis de expressão gênica podem se transformar em exames de rotina numa forma de triagem molecular.

ABSTRACT Translational research involves the interface between basic research and medical practice in order to generate innovative products or processes to introduce them into clinical protocols and health systems. The objective of this essay was to present an overview of transcriptomic advances, subsidized by the availability and use of new information technologies and molecular biology. In the search for accurate and less invasive diagnosis, transcriptomic tests use gene expression signatures to detect neurodegenerative diseases (Parkinson and Alzheimer), autoimmune (systemic lupus erythematosus, Wegener's granulomatosis), heart failure, autism and cancer (breast, colorectal, hepatic and lung). In the English health system the clinical guidelines incorporate eight transcriptomic tests, all with a focus on cancer. In Brazil genomic tests based on DNA sequences are regulated to diagnose congenital anomalies both in the Unified Health System and in supplementary health, but the molecular tests have not advanced in the scope of the diagnostic transcriptomics. The Brazilian health system should go beyond the tests of genomic analysis and begin the process of regulation of transcriptomic diagnostic technologies. In the future, diagnostic tests evaluating multiple gene expression profiles may become routine exams in a form of molecular screening.

Duathlon training model adapted for female rats: blood glucose-lactate correlations / Modelo de treinamento de duathlon adaptado para ratas: correlação de glicose-lactato no sangue / Modelo de entrenamiento de duatlón adaptado para ratones: correlación de glucosa-lactato en la sangre

ABSTRACT Objective: To propose a duathlon model adapted for rats (associated swimming and running training) and compare it with the individual activities carried out separately, considering the glucose uptake and serum lactate production mechanism. Methods: Twenty-eight 90-day-old Wistar rats with a mean weight of 150-200 g were used. The animals were divided into four groups: control group, swimming group, running group, and swimming/running group. These animals were adapted to their respective training programs for three days and underwent the 4-week training protocol soon afterwards. Pre- and post-training blood lactate and blood glucose analyses were performed at the end of each week. Statistical difference was considered when the p value was less than 0.01 (p <0.01). Results: There was a decrease in glycemic levels and an increase in lactate levels in the swimming and swimming/running groups throughout the training period, which did not occur in the running group. Conclusion: The duathlon model adapted for rats proved satisfactory in terms of the production and stabilization of blood lactate levels. Level of evidence II; Therapeutic Studies - Investigating the Results of Treatment.

RESUMO Objetivo: Propor um modelo de duathlon adaptado para ratos (treinamento associado de natação e corrida) e compará-lo com as modalidades praticadas isoladamente, considerando o mecanismo de consumo de glicose e produção de lactato sérico. Métodos: Foram utilizados vinte e oito ratos Wistar, com 90 dias de vida e peso médio de 150-200 g. Os animais foram divididos em quatro grupos: grupo controle, grupo de natação, grupo de corrida e grupo de natação/corrida. Esses foram adaptados aos seus respectivos treinos durante três dias e, logo depois, foram submetidos ao protocolo de treinamento com duração de quatro semanas. No final de cada semana, foram realizadas análises de lactato e glicose sanguínea pré- e pós- treinamento. A diferença estatística foi considerada quando o valor p era inferior a 0,01 (p <0,01). Resultados: Houve diminuição nos níveis de glicemia e aumento nos níveis de lactato nos grupos de natação e natação/corrida ao longo do período de treinamento, o que não ocorreu no grupo de corrida. Conclusão: Pode-se verificar que o modelo duathlon adaptado para ratos foi satisfatório em relação à produção e estabilização dos níveis sanguíneos de lactato. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados de tratamento.

RESUMEN Objetivo: Proponer un modelo de duatlón adaptado para ratones (entrenamiento asociado de natación y carrera) y compararlo con las modalidades practicadas aisladamente, considerando el mecanismo de consumo de glucosa y producción de lactato sérico. Métodos: Fueron utilizados veintiocho ratones Wistar, con 90 días de vida y peso promedio de 150-200 g. Los animales fueron divididos en cuatro grupos: grupo control, grupo de natación, grupo de carrera y grupo de natación/carrera. Esos fueron adaptados a sus respectivos entrenamientos durante tres días y, luego después, fueron sometidos al protocolo de entrenamiento con duración de cuatro semanas. Al final de cada semana, fueron realizados análisis de lactato y glucosa sanguínea pre y post entrenamiento. La diferencia estadística fue considerada cuando el valor p era inferior a 0,01 (p <0,01). Resultados: Hubo disminución en los niveles de glucemia y aumento en los niveles de lactato en los grupos de natación y natación/carrera a lo largo del período de entrenamiento, lo que no ocurrió en el grupo de carrera. Conclusión: Se puede verificar que el modelo duatlón adaptado para ratones fue satisfactorio con relación a la producción y estabilización de los niveles sanguíneos de lactato. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamento.

A compendium of physical exercise-related human genes: an 'omic scale analysis.

Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The study aimed to evaluate human genes linked to physical exercise in an 'omic scale, addressing biological questions to the generated database. Three literature databases were searched with the terms 'exercise', 'fitness', 'physical activity', 'genetics' and 'gene expression'. For additional references, papers were scrutinized and a text-mining tool was used. Papers linking genes to exercise in humans through microarray, RNA-Seq, RT-PCR and genotyping studies were included. Genes were extracted from the collected literature, together with information on exercise protocol, experimental design, gender, age, number of individuals, analytical method, fold change and statistical data. The 'omic scale dataset was characterized and evaluated with bioinformatics tools searching for gene expression patterns, functional meaning and gene clusters. As a result, a physical exercise-related human gene compendium was created, with data from 58 scientific papers and 5.147 genes functionally correlated with 17 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. While 50.9% of the gene set was up-regulated, 41.9% was down-regulated. 743 up- and 530 down-regulated clusters were found, some connected by regulatory networks. To summarize, up- and down-regulation was encountered, with a wide genomic distribution of the gene set and up- and down-regulated clusters possibly assembled by functional gene evolution. Physical exercise elicits a widespread response in gene expression.

Regulação gênica da via ampk pelo exercício físico: revisão sistemática e análise in silico / Ampk pathway gene regulation by physical exercise: systematic review and in silico analysis / Regulación génica de la vía ampk por el ejercicio físico: revisión sistemática y análisis in silico

RESUMO Introdução: Novos estudos de regulação gênica do exercício físico por meio de técnicas pós-genômicas em ensaios de resistência (endurance) e força caracterizam a transcriptômica do exercício físico. Entre os genes afetados, destacamos a via da proteína quinase ativada por AMP (AMPK), cuja ativação ocorre durante o exercício como resultado das alterações dos níveis de fosfato energético da fibra muscular. Objetivo: Avaliar a via de sinalização da AMPK por revisão sistemática da expressão de genes e análise in silico. Método: Foi efetuada uma revisão sistemática para avaliar a regulação gênica da via de sinalização AMPK, caracterizando os genes estudados na literatura, as variações de regulação obtidas, na forma de fold change e tipos de exercício usados. Resultados: A via de sinalização AMPK mostrou 133 genes no repositório KEGG (Kyoto Encyclopedia of Genes and Genomes), os quais foram confrontados com a revisão sistemática da literatura, totalizando 65 genes. Dezessete genes apresentaram UR e 24 mostraram DR com relação ao seu respectivo controle. Além destes, 20 genes estavam presentes nos trabalhos, apresentando tanto UR e DR e quatro genes não apresentaram dados de regulação. Verificou-se regulação específica em função do tipo de exercício efetuado. Discussão: Dos 133 genes da via AMPK, 48,8% foram amostrados nos trabalhos revisados, indicando que uma parte significativa da via é regulada pelo exercício. O estudo apresentou a regulação gênica básica de dois mecanismos para a recuperação energética, a biogênese mitocondrial e o bloqueio da gliconeogênese. Conclusão: Este trabalho mostrou que o exercício atua ativamente na via de sinalização da AMPK, na importância da regulação via PGC-1α e no papel de outros genes, regulando a expressão de mais da metade dos genes amostrados.

ABSTRACT Introduction: New studies of gene regulation by physical exercise through post-genomic techniques in endurance and strength tests characterize the physical exercise transcriptomics. Among the affected genes, we highlight the AMP-activated protein kinase (AMPK) pathway, the activation of which occurs during exercise because of changes in muscle fiber energetic phosphate levels. Objective: To evaluate the AMPK signaling pathway by systematic review of gene expression and in silico analysis. Method: A systematic review was performed in order to assess the gene regulation of AMPK signaling pathway, characterizing the genes studied in the literature, regulation variations obtained in the form of fold change, and types of exercise performed. Results: The AMPK signaling pathway showed 133 genes in the KEGG repository (Kyoto Encyclopedia of Genes and Genomes), which were compared with the systematic review of the literature, totaling 65 genes. Seventeen genes presented UR and 24 showed DR in relation to their respective control. In addition to these, 20 genes were present in the literature, presenting both UR and DR and four genes showed no regulatory data. Specific regulation was verified according to the type of exercises performed. Discussion: Of the 133 genes of the AMPK pathway, 48.8% were sampled in the revised studies indicating that a significant part of the pathway is regulated by exercise. The study presented the basic gene regulation of two mechanisms for energy recovery, mitochondrial biogenesis, and gluconeogenesis blockade. Conclusion: This work showed that the exercise actively works in the AMPK signaling pathway, in the importance of regulation via PGC-1α and in the role of other genes, regulating the expression of more than half of the genes sampled.

RESUMEN Introducción: Nuevos estudios de regulación génica del ejercicio físico por medio de técnicas pos-genómicas en ensayos de resistencia (endurance) y fuerza caracterizan la transcriptómica del ejercicio físico. Entre los genes afectados, destacamos la vía de la proteína quinasa activada por AMP (AMPK), cuya activación ocurre durante el ejercicio como resultado de las alteraciones de los niveles de fosfato energético de la fibra muscular. Objetivo: Evaluar la vía de señalización AMPK por revisión sistemática de la expresión de genes y análisis in silico. Método: Se ha efectuado una revisión para evaluar la regulación génica de la vía de señalización AMPK, caracterizando los genes estudiados en la literatura, las variaciones de regulación obtenidas en forma de fold change y tipos de ejercicios utilizados. Resultados: La vía de señalización AMPK mostró 133 genes en el repositorio KEGG (Kyoto Encyclopedia of Genes and Genomes), los cuales fueran confrontados con la revisión sistemática de la literatura, totalizando 65 genes. Diecisiete genes presentaron UR y 24 mostraron DR con respecto a su respectivo control. Además de estos, 20 genes estaban presentes en los trabajos, presentando tanto UR y DR y cuatro genes no presentaron dados de regulación. Se observó una regulación específica en función del tipo de ejercicio efectuado. Discusión: De los 133 genes de la vía AMPK, 48,8% fueron muestreados en los trabajos revisados, indicando que una parte significativa de la vía es regulada por el ejercicio. El estudio presentó la regulación génica básica de dos mecanismos para la recuperación energética, la biogénesis mitocondrial y el bloqueo de la gluconeogénesis. Conclusión: Este trabajo mostró que el ejercicio actúa activamente en la vía de señalización AMPK, en la importancia de la regulación vía factor PGC-1a y en el papel de otros genes, regulando la expresión de más de la mitad de los genes muestreados.

Análise da função pulmonar e estrutura micromecânica após 14 dias de restrição de movimento em ratas / Análisis de la función pulmonar y estructura micromecanica después de 14 días de restricción en el movimiento en ratas / Analysis of pulmonary function and micromechanics structure after 14 days of movement restriction in female rats

RESUMO A imobilização é uma condição que compromete diversos segmentos e sistemas orgânicos, inclusive o sistema respiratório, levando a alterações estruturais e funcionais. O objetivo deste estudo foi analisar a função pulmonar e estrutura micromecânica após 14 dias de restrição de movimento de ratas. Foram utilizados catorze ratas Wistar com massa corporal entre 210 g±50 g, distribuídas em dois grupos, compostos por (n=7) cada grupo: Controle (C) e Imobilizado (I). O procedimento de imobilização envolveu abdômen (e últimas costelas), pelve, quadril e joelho em extensão, além de tornozelo em flexão plantar, por duas semanas. Após esse período de imobilização, foi realizada a análise da função pulmonar por ventilador mecânico para pequenos animais (flexiVent) e manobras de recrutamento alveolar (MR). E, posteriormente, foram retiradas tiras do pulmão de cada animal para analisar a micromecânica pulmonar. Para a análise estatística, utilizou-se o teste t não pareado com significância estatística (p<0,05), expresso como média±erro padrão da média. O grupo I apresentou mudanças significantes nos parâmetros da resistência das vias aéreas (RN) pré-MR(C=0,067±0,003 cmH2O.s/mL, I=0,095±0,004 cmH2O.s/mL, p<0,05) e histerisividade (η) pré-MR(C=0,203±0,004 cmH2O.s/mL, I=0,248±0,013 cmH2O.s/mL, p<0,05), que retornaram a seus valores de normalidade pós-MR, considerando-se RN pós-MR (C=0,064±0,003 cmH2O.s/mL, I=0,065±0,004 cmH2O.s/mL, p<0,05) e η (C=0,209±0,005 cmH2O.s/mL, I=0,214±0,007 cmH2O.s/mL, p<0,05). Conclui-se que a imobilização acarreta alterações funcionais reversíveis no sistema respiratório após 14 dias de restrição de movimento, o que é evidenciado pela redução de RN e η pós-MR.

RESUMEN La inmobilización es una condición que compromete diversos segmentos y sistemas orgánicos incluso el sistema respiratorio, llevando a alteraciones estructurales y funcionales. El objectivo de este estudio fue analizar la función pulmonar y estructura micromecánica después de 14 días de restricción en el movimiento de ratas. Fueron utilizados catorce ratas Wistar con masa corporal entre 210 g±50 g, distribuidas en dos grupos, compuestos por (n=7) cada grupo: Control (C) y Inmobilizado (I). El procedimiento de inmobilización envolvió el abdomen (y últimas costillas), la pelvis, la cadera y la rodilla en extensión y el tobillo en flexión plantar el periodo de dos semanas. Después del periodo de inmobilización fue realizado el análisis de la función pulmonar por medio del ventilador mecánico para pequeños animales flexVent y manobras de recrutamiento alveolar (MR). Posteriormente, fueron retirados pedazos del pulmón de cada animal para análisis de la micromecánica pulmonar. Para el análisis estadística se utilizó la prueba t no pareada con significación estadística (p<0,05), expresa como media±error patrón de la media. El grupo I presentó cambios significativos en los parámetros de la resistencia de las vias aéreas (RN) pre-MR (C=0,067±0,003 cmH2O.s/mL, I=0,095±0,004 cmH2O.s/mL, p<0,05) y histerisividade (η) pre-MR(C=0,203±0,004 cmH2O.s/mL, I=0,248±0,013 cmH2O.s/mL, p<0,05), que retornaron a sus valores de normalidad después de la MR. RN post-MR (C=0,064±0,003 cmH2O.s/mL, I=0,065±0,004 cmH2O.s/mL, p<0,05) y η (C=0,209±0,005 cmH2O.s/mL, I=0,214±0,007 cmH2O.s/mL, p<0,05). Se concluye que la inmobilización conlleva alteraciones funcionales reversibles en el sistema respiratorio, después de 14 días de restricción en el movimiento evidenciado por la reducción de la RN y η después de la MR.

ABSTRACT Immobilization is a condition that affects several segments and organic systems, including the respiratory system, leading to structural and functional alterations. The purpose of this study was to analyze pulmonary function and micromechanical structure after 14 days of movement restriction in rats. Fourteen female Wistar rats with body mass between 210±50 g were used, divided into two groups, composed of (n=7) each group: Control (C) and Immobilized (I). The immobilization procedure involved the abdomen (and last ribs), pelvis, hip and knee extension and the ankle in plantar flexion in the two week period. After the immobilization period, an analysis of the pulmonary function was performed using a mechanical ventilator for small animals, flexVent, and alveolar recruitment maneuvers. Subsequently, lung strips were removed from each animal for pulmonary micromechanics analysis. Statistical analysis was performed using the unpaired t test with p<0.05, expressed as mean±standard error of the mean. Group I presented significant changes in the parameters of airway resistance (Raw) Pre RM (C=0.067±0.003 cmH2O.s/mL, I=0.095±0.004 cmH2O.s/mL, p<0.05) and Hysteresivity (η) Pre RM (C=0.203±0.004 cmH2O.s/mL, I=0.248±0.013 cmH2O.s/mL, p<0.05), which returned to their normal values after RM. Raw Post RM (C=0.064±0.003 cmH2O.s/mL, I=0.065±0.004 cmH2O.s/mL, p<0.05) and η (C=0.209±0.005 cmH2O.s/mL, I=0.214±0.007 cmH2O.s/mL, p<0.05). It is concluded that immobilization causes reversible functional changes in the respiratory system after 14 days of movement restriction evidenced by the reduction of RN and η after RM.

Regulation of muscle plasticity and trophism by fatty acids: A short review.

The skeletal muscle tissue has a remarkable ability to alter its plastic structural and functional properties after a harmful stimulus, regulating the expression of proteins in complex events such as muscle regeneration. In this context, considering that potential therapeutic agents have been widely studied, nutritional strategies have been investigated in order to improve the regenerative capacity of skeletal muscle. There is evidence of the modulatory action of fatty acids, such that oleic and linoleic acids, that are abundant in Western diets, on muscle function and trophism. Thus, fatty acids appear to be potential candidates to promote or impair the recovery of muscle mass and function during regeneration, since they modulate intracellular pathways that regulate myogenesis. This study is the first to describe and discuss the effect of fatty acids on muscle plasticity and trophism, with emphasis on skeletal muscle regeneration and in vitro differentiation of muscle cells.

Regulation of muscle plasticity and trophism by fatty acids: A short review / Regulação da plasticidade e do trofismo muscular pelos ácidos graxos: uma breve revisão

Summary The skeletal muscle tissue has a remarkable ability to alter its plastic structural and functional properties after a harmful stimulus, regulating the expression of proteins in complex events such as muscle regeneration. In this context, considering that potential therapeutic agents have been widely studied, nutritional strategies have been investigated in order to improve the regenerative capacity of skeletal muscle. There is evidence of the modulatory action of fatty acids, such that oleic and linoleic acids, that are abundant in Western diets, on muscle function and trophism. Thus, fatty acids appear to be potential candidates to promote or impair the recovery of muscle mass and function during regeneration, since they modulate intracellular pathways that regulate myogenesis. This study is the first to describe and discuss the effect of fatty acids on muscle plasticity and trophism, with emphasis on skeletal muscle regeneration and in vitro differentiation of muscle cells.

Resumo O tecido muscular esquelético possui a notável capacidade plástica de alterar suas propriedades estruturais e funcionais após um estímulo lesivo, regulando a expressão de proteínas durante eventos complexos como a regeneração muscular. Nesse contexto, considerando que possíveis agentes terapêuticos vêm sendo amplamente estudados, estratégias nutricionais têm sido investigadas na perspectiva de melhorar a capacidade regenerativa do músculo esquelético. Há evidências da ação modulatória dos ácidos graxos, como os ácidos oleico e linoleico, que são abundantes nas dietas ocidentais, sobre a função muscular e o trofismo. Nesse sentido, os ácidos graxos parecem ser potenciais candidatos para promover ou prejudicar a recuperação da massa e a função muscular durante a regeneração, uma vez que modulam vias intracelulares reguladoras da miogênese. Este trabalho é o primeiro a descrever e discutir o efeito dos ácidos graxos sobre a plasticidade e o trofismo muscular, com ênfase na regeneração do músculo esquelético e na diferenciação de células musculares in vitro.

ADAPTAÇÃO DO MÚSCULO ESQUELÉTICO AO EXERCÍCIO FÍSICO: CONSIDERAÇÕES MOLECULARES E ENERGÉTICAS / ADAPTATION OF SKELETAL MUSCLE TO PHYSICAL EXERCISE: MOLECULAR AND ENERGY CONSIDERATIONS / ADAPTACIÓN DEL MÚSCULO ESQUELÉTICO AL EJERCICIO FÍSICO: CONSIDERACIONES MOLECULARES Y ENERGÉTICAS

RESUMO Os benefícios para a saúde e as adaptações fisiológicas ao exercício regular são amplamente conhecidos e, com o advento das ciências ômicas e moleculares, revelou-se uma complexa rede de vias de sinalização e moléculas reguladoras que coordenam a resposta adaptativa do músculo esquelético ao exercício. As mudanças orgânicas transientes, porém, são cumulativas no pós-exercício. Elas incluem, de forma principal, a transcrição de genes relacionados aos fatores regulatórios da miogênese, ao metabolismo de carboidratos, à mobilização de gorduras, ao transporte e oxidação de substratos, ao metabolismo mitocondrial através da fosforilação oxidativa e, por fim, à regulação transcricional de genes envolvidos na biogênese mitocondrial. Tendo em vista o grande impacto científico, resumiram-se neste trabalho, além de algumas das principais respostas moleculares sofridas pelo músculo esquelético com o exercício físico, fatores que coordenam a plasticidade muscular para o ganho de desempenho. Foram citadas dezenas de biomarcadores ligados a alguns aspectos moleculares das adaptações do músculo esquelético ao exercício físico, algumas principais vias sinalizadoras e o papel mitocondrial, revelando alguns novos paradigmas para o entendimento desta área científica.

ABSTRACT The health benefits and physiological adaptations to regular physical exercise are widely known, and with the advent of the omic and molecular sciences, a complex network of signaling pathways and regulatory molecules that coordinate the adaptive response of skeletal muscle to exercise has been revealed. Transient organic changes, however, are cumulative in the post-exercise period. They mainly include transcription of genes related to regulatory factors of myogenesis, carbohydrate metabolism, fat mobilization, transport and oxidation of substrates, mitochondrial metabolism through oxidative phosphorylation, and finally, the transcriptional regulation of genes involved in mitochondrial biogenesis. Given their great scientific impact, in addition to some of the main molecular responses experienced by the skeletal muscle to exercise, factors that coordinate muscle plasticity for performance gain were summarized in this work. This review mentioned dozens of biomarkers linked to some molecular aspects of skeletal muscle adaptations to physical exercise, some major signaling pathways and the role of mitochondria, revealing some new paradigms for the understanding of this field of science.

RESUMEN Los beneficios para la salud y las adaptaciones fisiológicas al ejercicio regular son ampliamente conocidos y, con el advenimiento de las ciencias ómicas y moleculares, se ha revelado una compleja red de vías de señalización y moléculas reguladoras que coordinan la respuesta adaptativa del músculo esquelético al ejercicio físico. Los cambios orgánicos transitorios, sin embargo, son acumulativos después del ejercicio. Ellos incluyen principalmente la trascripción de genes relacionados a los factores de regulación de la miogénesis, metabolismo de carbohidratos, movilización de grasas, transporte y oxidación de substratos, metabolismo mitocondrial por la fosforilación oxidativa y, en última instancia, la regulación transcripcional de genes involucrados en la biogénesis mitocondrial. Teniendo en cuenta el gran impacto científico, se resumió en este trabajo, además de algunas de las principales respuestas moleculares experimentadas por el músculo esquelético con el ejercicio físico, factores que coordinan la plasticidad muscular en la ganancia del rendimiento. Se citaron decenas de biomarcadores relacionados con algunos aspectos moleculares de las adaptaciones del músculo esquelético al ejercicio físico, algunas de las principales vías de señalización y el papel mitocondrial, revelando algunos nuevos paradigmas para el entendimiento de esta área científica.