ABO blood group and link to COVID-19: A comprehensive review of the reported associations and their possible underlying mechanisms.

ABO blood group is long known to be an influencing factor for the susceptibility to infectious diseases, and many studies have been describing associations between ABO blood types and COVID-19 infection and severity, with conflicting findings. This narrative review aims to summarize the literature regarding associations between the ABO blood group and COVID-19. Blood type O is mostly associated with lower rates of SARS-CoV-2 infection, while blood type A is frequently described as a risk factor. Although results regarding the risk of severe outcomes are more variable, blood type A is the most associated with COVID-19 severity and mortality, while many studies describe O blood type as a protective factor for the disease progression. Furthermore, genetic associations with both the risk of infection and disease severity have been reported for the ABO locus. Some underlying mechanisms have been hypothesized to explain the reported associations, with incipient experimental data. Three major hypotheses emerge: SARS-CoV-2 could carry ABO(H)-like structures in its envelope glycoproteins and would be asymmetrically transmitted due to a protective effect of the ABO antibodies, ABH antigens could facilitate SARS-CoV-2 interaction with the host' cells, and the association of non-O blood types with higher risks of thromboembolic events could confer COVID-19 patients with blood type O a lower risk of severe outcomes. The hypothesized mechanisms would affect distinct aspects of the COVID-19 natural history, with distinct potential implications to the disease transmission and its management.

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.

Defesa antioxidante no fígado de ratos Wistar pós inibição por Alopurinol / Antioxidant defense in Wistar rats liver after Alopurinol inhibition

As espécies reativas de oxigênio (EROs) são radicais livres derivadas do oxigênio. O fármaco Alopurinol (ALO) possui um efeito inibidor da enzima Xantina Oxidase, uma das vias da produção de EROs. Para combater esse ataque oxidativo no nosso organismo, existe uma defesa antioxidante enzimática, composta pelas enzimas Superóxido dismutase (SOD), Catalase (CAT) e Glutationa Peroxidase (GPX). O objetivo do presente estudo foi analisar os efeitos do alopurinol na defesa antioxidante no fígado de ratos Wistar. Foram utilizados 20 ratos machos divididos em dois grupos: Controle (C) e Alopurinol (ALO). A droga foi administrada para os animais do grupo ALO, enquanto que no grupo C houve uma administração de veículo (salina), ambos durante 3 dias. Os resultados apontaram uma redução significativa na atividade das enzimas antioxidantes no grupo ALO em comparação ao grupo C. A partir desses resultados sugeriu-se que o alopurinol foi eficiente na inibição de EROs.

Reactive oxygen species (ROS) are free radicals derived from oxygen. The drug Allopurinol (ALO) has an inhibitory effect of the enzyme Xanthine Oxidase, one of the routes of ROS production. To combat this oxidative attack in our body, there is an enzymatic antioxidant defense, composed by the enzymes Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX). The aim of the present study was to analyze the effects of allopurinol on the antioxidant defense in the liver of Wistar rats. Twenty male rats were divided into two groups: Control (C) and Allopurinol (ALO). The drug was administered to the animals of the ALO group, while in group C there was a vehicle (saline) administration, both for 3 days. The results indicated a significant reduction in the activity of the antioxidant enzymes in the ALO group compared to the group C. From these results it was suggested that allopurinol was efficient in inhibiting ROS.

Defesa antioxidante no fígado de ratos Wistar pós inibição por Alopurinol / Antioxidant defense in Wistar rats liver after Alopurinol inhibition

As espécies reativas de oxigênio (EROs) são radicais livres derivadas do oxigênio. O fármaco Alopurinol (ALO) possui um efeito inibidor da enzima Xantina Oxidase, uma das vias da produção de EROs. Para combater esse ataque oxidativo no nosso organismo, existe uma defesa antioxidante enzimática, composta pelas enzimas Superóxido dismutase (SOD), Catalase (CAT) e Glutationa Peroxidase (GPX). O objetivo do presente estudo foi analisar os efeitos do alopurinol na defesa antioxidante no fígado de ratos Wistar. Foram utilizados 20 ratos machos divididos em dois grupos: Controle (C) e Alopurinol (ALO). A droga foi administrada para os animais do grupo ALO, enquanto que no grupo C houve uma administração de veículo (salina), ambos durante 3 dias. Os resultados apontaram uma redução significativa na atividade das enzimas antioxidantes no grupo ALO em comparação ao grupo C. A partir desses resultados sugeriu-se que o alopurinol foi eficiente na inibição de EROs.(AU)

Reactive oxygen species (ROS) are free radicals derived from oxygen. The drug Allopurinol (ALO) has an inhibitory effect of the enzyme Xanthine Oxidase, one of the routes of ROS production. To combat this oxidative attack in our body, there is an enzymatic antioxidant defense, composed by the enzymes Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX). The aim of the present study was to analyze the effects of allopurinol on the antioxidant defense in the liver of Wistar rats. Twenty male rats were divided into two groups: Control (C) and Allopurinol (ALO). The drug was administered to the animals of the ALO group, while in group C there was a vehicle (saline) administration, both for 3 days. The results indicated a significant reduction in the activity of the antioxidant enzymes in the ALO group compared to the group C. From these results it was suggested that allopurinol was efficient in inhibiting ROS.(AU)

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.

Sensorial, structural and functional response of rats subjected to hind limb immobilization.

AIMS: This study analyzed the sensorial, structural and functional response of rats subjected to paw immobilization. MAIN METHODS: Animal pelvis, hip, knee and ankle were immobilized using waterproof tape during two weeks for assessment of sensorial response to thermal (hot plate test) and mechanical stimuli (Von Frey test), motor system structure (histology and radiography) and muscle function (soleus contractility). KEY FINDINGS: Disuse animals became more responsive to thermal stimuli (49%), although less responsive to mechanical challenge (58%). Disuse animals showed local injuries such as reduction in muscle fiber diameter (16.7% in gastrocnemius, 5.7% in soleus), contractile activity (55% of the control maximal tonic contraction) and tibia cortical thickness (9.3%), besides increased nitrite:protein ratio, suggestive of protein degradation. Disuse also evoked systemic adaptations that include increase in serum lactate dehydrogenase (36.1%) and alkaline phosphatase (400%), but reduction in calcium (8.4%) and total serum protein (5.5%), especially albumin (34.2%). SIGNIFICANCE: Two weeks of functional paw disuse leads to local and systemic harmful adaptive changes in sensorial and structural systems. This study brings new insights into nervous and motor system mechanism associated with therapeutic limb immobilization in muscle and skeletal pathological conditions.

Resposta curso-temporal da enzima catalase no músculo esquelético de ratos após uma sessão de exercício exaustivo / Time-course response of catalase enzyme in skeletal muscle of rats after exhaustive exercise session

Studies show that exhaustive exercise prints in an imbalance between free radicals and antioxidant defense system. One of the enzymes responsible for the defense system is catalase (CAT) which detoxifica hydrogen peroxide in skeletal muscle avoiding possible damage. The aim of this study was to assess the time course of response catalase in skeletal muscle of mice after an exhaustive exercise session. They used 36 male Wistar rats with 60 days old and weighing 220-240g, kept in light / dark 12h / 12h with water and food ad libitum. The animals were divided into six groups: control group; immediately after exercise (0h); 6h; 12h; 24h; 48 hours after exercise. These have been adapted for two weeks on a treadmill for 48 hours after the animals and adaptation undergo a workout. The portions of red gastrocnemius muscle were dissected and stored in liquid nitrogen. The gene expression analysis was performed by PCR in real time. To analyze the enzymatic activity of CAT, the cultures were placed in a spectrophotometer at the absorbance value at 240 nm. The results were evaluated by analysis of variance (ANOVA - oneway) and post Tukey test (p <0.05). The results showed large capacity regulation of this antioxidant enzyme, indicating a significant increase in expression of CAT 6h after exercise (p <0.05), as well as enzyme activity also increased by 6 hours after exercise (p <0.05) compared with the control, concluding that in the first hour after exercise has been possible to identify a defense response in skeletal muscle after exhaustive exercise.

Redução do uso de animais através da bioinformática: técnicas in-silico apontam alvos moleculares / Reduction in the utilization of animals through bioinformatics: in-silico techniques point towards molecular targets

Model animals are indispensable in the advancement of life sciences. Computational analyses can save time and reduce the number of animals needed. Bioinformatics offer tools that support research through in-silico evaluations. Our aim was to study the function of exercise-linked genes, focusing on disease pathways, envisaging the discovery of new molecular targets for the use in animal model studies. This research was part of two projects approved by the local Ethics Committee (CEUA/UECE) in 04/2014 (1592060/2014) and 07/2015 (2542310/2015). Human genes linked to physical exercise were classified by the pathways using the enrichment tool Enrichnet. Statistical analyses (ANOVA) were used using the Fisher test (q-value). Strong correlations were found with neurodegenerative, cardiovascular and immunologic diseases. Within neurodegenerative diseases, physical exercise was found to be linked to Parkinson’s (q-value 1.6 X10-17), Alzheimer’s (q-value 3.9 X10-16) and Huntington disease (q-value 1.9 X10-15). Within cardiovascular diseases linked to exercise there is hypertrophic cardiomyopathy (q-value 8.5 X10-15). A large number of genes linked to exercise were found to participate in disease linked metabolic pathways. Concluding, after evaluating genes linked to physical exercise and disease pathways, new molecular targets for the use in model animal studies were revealed.

Redução do uso de animais através da bioinformática: técnicas in-silico apontam alvos moleculares / Reduction in the utilization of animals through bioinformatics: in-silico techniques point towards molecular targets

Model animals are indispensable in the advancement of life sciences. Computational analyses can save time and reduce the number of animals needed. Bioinformatics offer tools that support research through in-silico evaluations. Our aim was to study the function of exercise-linked genes, focusing on disease pathways, envisaging the discovery of new molecular targets for the use in animal model studies. This research was part of two projects approved by the local Ethics Committee (CEUA/UECE) in 04/2014 (1592060/2014) and 07/2015 (2542310/2015). Human genes linked to physical exercise were classified by the pathways using the enrichment tool Enrichnet. Statistical analyses (ANOVA) were used using the Fisher test (q-value). Strong correlations were found with neurodegenerative, cardiovascular and immunologic diseases. Within neurodegenerative diseases, physical exercise was found to be linked to Parkinsons (q-value 1.6 X10-17), Alzheimers (q-value 3.9 X10-16) and Huntington disease (q-value 1.9 X10-15). Within cardiovascular diseases linked to exercise there is hypertrophic cardiomyopathy (q-value 8.5 X10-15). A large number of genes linked to exercise were found to participate in disease linked metabolic pathways. Concluding, after evaluating genes linked to physical exercise and disease pathways, new molecular targets for the use in model animal studies were revealed.(AU)

Resposta curso-temporal da enzima catalase no músculo esquelético de ratos após uma sessão de exercício exaustivo / Time-course response of catalase enzyme in skeletal muscle of rats after exhaustive exercise session

Studies show that exhaustive exercise prints in an imbalance between free radicals and antioxidant defense system. One of the enzymes responsible for the defense system is catalase (CAT) which detoxifica hydrogen peroxide in skeletal muscle avoiding possible damage. The aim of this study was to assess the time course of response catalase in skeletal muscle of mice after an exhaustive exercise session. They used 36 male Wistar rats with 60 days old and weighing 220-240g, kept in light / dark 12h / 12h with water and food ad libitum. The animals were divided into six groups: control group; immediately after exercise (0h); 6h; 12h; 24h; 48 hours after exercise. These have been adapted for two weeks on a treadmill for 48 hours after the animals and adaptation undergo a workout. The portions of red gastrocnemius muscle were dissected and stored in liquid nitrogen. The gene expression analysis was performed by PCR in real time. To analyze the enzymatic activity of CAT, the cultures were placed in a spectrophotometer at the absorbance value at 240 nm. The results were evaluated by analysis of variance (ANOVA - oneway) and post Tukey test (p <0.05). The results showed large capacity regulation of this antioxidant enzyme, indicating a significant increase in expression of CAT 6h after exercise (p <0.05), as well as enzyme activity also increased by 6 hours after exercise (p <0.05) compared with the control, concluding that in the first hour after exercise has been possible to identify a defense response in skeletal muscle after exhaustive exercise.(AU)