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ABSTRACT Objectives: The effects of weightlessness on the liver were studied using a tail suspension (TS) male mouse model. Methods: The effects of 0-, 2- and 4-week TS (CON, TS2 and TS4 groups) on glycogen and lipid content, as well as on the molecular processes of the synthesis and degradation pathways, were examined. Results: (1) The number of glycogenosomes under ultrastructure and the glycogen content were considerably larger in the TS4 group than in the other two groups. (2) In the TS4 group, glycogen synthase activity remained constant while glycogen phosphorylase activity dropped, indicating that glycogen breakdown was reduced. (3) The livers of the TS2 group had the highest lipid and triglyceride content, indicating lipid buildup in the liver at this time. (4) In the TS2 group, the activities of the fatty acid synthesis-related factors acetyl-CoA carboxylase and fatty acid synthase increased, while hepatic lipase decreased, indicating that lipid synthesis increased, while decomposition decreased. (5) In the TS2 group, the protein expression of glucose transporters 1 and 2 increased. Conclusions: From TS2 weeks to TS4 weeks, the main energy consumption mode in the livers of mice transitioned from glucose metabolism to lipid metabolism as glucose use decreased. Level of evidence II; Comparative prospective study.

RESUMEN Objetivos: Se estudiaron los efectos de la antigravedad en el hígado utilizando un modelo de ratón macho en prueba de suspensión de la cola (TS, tail suspension). Métodos: Se examinaron los efectos de la TS a las 0, 2 y 4 semanas (grupos CON, TS2 y TS4) sobre el contenido de glucógeno y lípidos, así como sobre los procesos moleculares de las vías de síntesis y degradación. Resultados: (1) El número de glucogenosomas ultraestructurales y el contenido de glucógeno fueron expresivamente más altos en el grupo TS4 que en los otros dos grupos. (2) En el grupo TS4, la actividad de la glucógeno sintasa se mantuvo constante, mientras que la actividad de la glucógeno fosforilasa disminuyó, lo que indica que la degradación del glucógeno se redujo. (3) Los hígados del grupo TS2 presentaron el mayor contenido de lípidos y triglicéridos, lo que indica la acumulación de lípidos en el hígado en ese momento. (4) En el grupo TS2, la actividad de los factores relacionados con la síntesis de ácidos grasos acetil-CoA carboxilasa y ácido graso sintasa aumentó, mientras que la lipasa hepática disminuyó, indicando que la síntesis de lípidos aumentó mientras que la descomposición disminuyó. (5) En el grupo TS2, la expresión proteica de los transportadores de glucosa 1 y 2 aumentó. Conclusiones: Desde la semana TS2 hasta la semana TS4, el principal modo de consumo de energía en el hígado de los ratones pasó del metabolismo de la glucosa al metabolismo de los lípidos a medida que disminuía el uso de la glucosa. Nivel de Evidencia II, Estudio retrospectivo comparativo.

RESUMO Objetivos: Os efeitos da antigravidade no fígado foram estudados usando um modelo de camundongo macho com a suspensão pela cauda (TS, tail suspension). Métodos: Foram examinados os efeitos da TS em 0, 2 e 4 semanas (grupos CON, TS2 e TS4) sobre o conteúdo de glicogênio e lipídios, bem como nos processos moleculares das vias de síntese e degradação. Resultados: (1) O número de glicogenossomos ultraestruturais e o teor de glicogênio foram expressivamente maiores no grupo TS4 do que nos outros dois grupos. (2) No grupo TS4, a atividade de glicogênio sintase permaneceu constante, enquanto a atividade de glicogênio fosforilase caiu, indicando que a degradação do glicogênio foi reduzida. (3) Os fígados do grupo TS2 tiveram o maior teor lipídico e de triglicérides, indicando acúmulo de lipídios no fígado no momento. (4) No grupo TS2, a atividade dos fatores relacionados com a síntese de ácidos graxos acetil-CoA carboxilase e ácido graxo sintase aumentaram, enquanto a lipase hepática diminuiu, indicando que a síntese de lipídios aumentou, enquanto a decomposição diminuiu. (5) No grupo TS2, a expressão proteica dos transportadores de glicose 1 e 2 aumentou. Conclusões: De TS2 semanas para TS4 semanas, o principal modo de consumo de energia no fígado de camundongos passou do metabolismo da glicose para o metabolismo lipídico, à medida que o uso de glicose diminuiu. Nível de evidência II, Estudo retrospectivo comparativo.

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Gravity plays a crucial role in physiology. The lack of gravity, like in long duration spaceflight missions, cause pathologies in e.g., the musculoskeletal system, cardiovascular deconditioning, immune system deprivation or brain abnormalities, to just mention a few. The application of artificial gravity through short-arm human centrifugation (SAHC) has been studied as a possible countermeasure to treat spaceflight deconditioning. However, hypergravity protocols applied by using SAHC have also been used to treat different, ground-based pathologies. Such gravitational therapies have been applied in Uruguay for more than four decades now. The aim of this overview is to summarize the most important findings about the effects of gravitational therapy in different, mainly vascular based pathologies according to the experience in the Gravitational Therapy Center and to discuss the current research in the field of hypergravity applications in medicine but also as multisystem countermeasure for near weightlessness pathologies. New insight is needed on the use of hypergravity in medicine and space research and application.

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BACKGROUND: Microbes threaten human health in space exploration. Studies have shown that Proteus mirabilis has been found in human space habitats. In addition, the biological characteristics of P. mirabilis in space have been studied unconditionally. The simulated microgravity environment provides a platform for understanding the changes in the biological characteristics of P. mirabilis. OBJECTIVE: This study intends to explore the effect of simulated microgravity on P. mirabilis, the formation of P. mirabilis biofilm, and its related mechanism. METHODS: The strange deformable rods were cultured continuously for 14 days under microgravity simulated in high-aspect rotating vessels (HARVs). The morphology, growth rate, metabolism, and biofilm formation of the strain were measured, and the phenotypic changes of P. mirabilis were evaluated. Transcriptome sequencing was used to detect differentially expressed genes under simulated microgravity and compared with phenotype. RESULTS: The growth rate, metabolic ability, and biofilm forming ability of P. mirabilis were lower than those of normal gravity culture under the condition of simulated microgravity. Further analysis showed that the decrease of growth rate, metabolic ability, and biofilm forming ability may be caused by the downregulation of related genes (pstS, sodB, and fumC). CONCLUSION: The simulated microgravity condition enables us to explore the potential relationship between bacterial phenotype and molecular biology, thus opening up a suitable and constructive method for medical fields that have not been explored before. It provides a certain strategy for the treatment of P. mirabilis infectious diseases in space environment by exploring the microgravity of P. mirabilis.

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The human body experiences physiological changes under microgravity environment that phenocopy aging on Earth. These changes include early onset osteoporosis, skeletal muscle atrophy, cardiac dysfunction, and immunosenescence, and such adaptations to the space environment may pose some risk to crewed missions to Mars. To investigate the effect of microgravity on aging, many model organisms have been used such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and mice. Herein we report that the budding yeast Saccharomyces cerevisiae show decreased replicative lifespan (RLS) under simulated microgravity in a clinostat. The reduction of yeast lifespan is not a result of decreased tolerance to heat shock or oxidative stress and could be overcome either by deletion of FOB1 or calorie restriction, two known interventions that extend yeast RLS. Deletion of the sirtuin gene SIR2 worsens the simulated microgravity effect on RLS, and together with the fob1Δ mutant phenotype, it suggests that simulated microgravity augments the formation of extrachromosomal rDNA circles, which accumulate in yeast during aging. We also show that the chronological lifespan in minimal medium was not changed when cells were grown in the clinostat. Our data suggest that the reduction in longevity due to simulated microgravity is conserved in yeast, worms, and flies, and these findings may have potential implications for future crewed missions in space, as well as the use of microgravity as a model for human aging.

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Se presenta este artículo de revisión con base en la evidencia científica actual sobre medicina espacial enfocada en fisiología humana y sus contramedidas. Por lo cual se realizó una búsqueda bibliográfica no sistemática de artículos científicos y libros de investigación en inglés-español de los últimos 7 años, que detallan su aplicación en seres humanos, modelos murinos y experimentos in vitro. Se tomaron en cuenta las condiciones del ambiente espacial como microgravedad y radiación que producen considerables cambios fisiológicos en el sistema cardiovascular (redistribución de líquidos, remodelación cardiovascular, arritmias); nervioso (sensitivomotores, neurosensoriales, neurovestibulares); respiratorio (cambios de volúmenes y capacidades); renal (litiasis); musculoesquelético (atrofia muscular, osteoporosis); hematológico (anemia); inmunológico (desregulación inmune) y digestivo (alteración de la microbiota intestinal). Además, existen procesos biológicos, moleculares y genéticos aún por explorar, para conocer y mitigar los mecanismos inciertos desencadenados en ambientes extremos y peligrosos. Por lo tanto, es una prioridad desarrollar e implementar contramedidas para reducir los efectos nocivos en la salud, con el objetivo de garantizar la adaptación, seguridad y performance del astronauta durante futuros viajes espaciales.

This Review Article is presented based on current scientific evidence on space medicine focused on human physiology and its countermeasures. Therefore, a non-systematic bibliographic search of scientific articles and research books in English-Spanish of the last 7 years was carried out, detailing their application in humans, murine models and in vitro experiments. The conditions of the space environment such as microgravity and radiation that produce considerable physiological changes in the cardiovascular system (redistribution of fluids, cardiovascular remodeling, arrhythmias) were taken into account; nervous (sensorimotor, neurosensory, neurovestibular); respiratory (volume and capacity changes); renal (lithiasis); musculoskeletal (muscular atrophy, osteoporosis); hematological (anemia); immunological (immune dysregulation) and digestive (intestinal microbiota disorder). In addition, there are biological, molecular and genetic processes still to be explored, in order to know and mitigate the uncertain mechanisms triggered in extreme and dangerous environments. Therefore, it is a priority to develop and implement countermeasures to reduce the harmful effects on health, with the aim of guaranteeing the astronaut's adaptation, safety and performance during future space flights.

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After a short summary of the multifactorial models of maximal O2 consumption (VO2max) limitation, microgravity exposure is discussed as a convenient experimental condition to test these models. The following points are highlighted: 1) The decrease of (VO2max) in microgravity concerns specifically exercise performed in upright posture upon resumption of gravity exposure; 2) The decrease of (VO2max) after microgravity exposure has two components: one is fast and is related to cardiovascular adaptation, the other is slow and is related to the development of muscle atrophy; 3) (VO2max) does not decrease during microgravity or in supine posture upon resumption of gravity exposure, if the time in microgravity is sufficiently short; 4) cardiovascular oxygen transport accounts for 70% of (VO2max) limitation also after microgravity exposure.

Luego de un breve resumen de los modelos multifactoriales de la limitación del consumo máximo de oxígeno (VO2max), se analiza la exposición a la microgravedad como condición experimental conveniente para evaluar tales modelos. Se destacan los siguientes aspectos: 1) El decrecimiento en la microgravedad tiene que ver específicamente con los ejercicios realizados en posición vertical después de reanudar la exposición a la gravedad; 2) El decrecimiento posterior a la exposición a la microgravedad tiene dos componentes: uno es rápido y está relacionado con la adaptación cardiovascular, el otro es lento y está relacionado con la aparición de la atrofia muscular; 3) No decrece durante la microgravedad o en posición supina después de reanudarse la exposición a la gravedad, siempre que el tiempo transcurrido en microgravedad sea suficientemente corto; 4) el transporte de oxígeno cardiovascular representa el 70 % de la limitación también después de la exposición a la microgravedad.

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Maintaining health in microgravity and overcoming environmental hazards such as cosmic radiation are essential for long-term space flight. Recent studies have focused on the involvement of hypoxia-inducible factor (HIF)-1 in altered gravity using cell-based or in vivo mouse model systems. HIF-1alpha and its target downstream gene expression are differentially expressed in hypergravity and microgravity. Nevertheless, underlying molecular mechanism of HIF-1alpha involvement is still unclear. Herein, we analyzed the 2019 Science paper by Garrett-Bakelman and coauthors in which NASA performed multidimensional analyses of long-term human spaceflight in identical twin astronauts. Correlations were found between the expression of HIF-1alpha related cytokines and prolonged space flight. We hypothesize that HIF-1alpha is a molecular target for the development of therapeutics to prevent the detrimental effects of microgravity and cosmic radiation on astronauts during long-term space flight.

Mantener la salud en microgravedad y superar los peligros ambientales como la radiación cósmica son esenciales para los vuelos espaciales a largo plazo. Estudios recientes se han centrado en la participación del factor inducible por hipoxia (HIF) -1 en la gravedad alterada utilizando sistemas de modelos de ratones basados en células o in vivo. HIF-1alpha y su expresión génica secuencial objetivo se expresan diferencialmente en hipergravedad y microgravedad. Sin embargo, el mecanismo molecular subyacente de la participación de HIF-1alpha aún no está claro. Aquí, analizamos el artículo de Ciencia de 2019 de Garrett-Bakelman y coautores en el que la NASA realizó análisis multidimensionales de vuelos espaciales humanos a largo plazo en astronautas gemelos idénticos. Se encontraron correlaciones entre la expresión de citoquinas relacionadas con HIF-1alpha y el vuelo espacial prolongado. Presumimos que HIF-1alpha es un objetivo molecular para el desarrollo de terapias para prevenir los efectos perjudiciales de la microgravedad y la radiación cósmica en los astronautas durante los vuelos espaciales a largo plazo.

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Resumen La alimentación de los primeros astronautas de la NASA es un testimonio de su fortaleza. John Glenn fue el primer hombre de Norte América que comió en un estado de microgravedad, lo cual no fue nada fácil, además de contar con un menú limitado. Él, al igual que los astronautas de la expedición Mercury tuvieron que basar su alimentación en cubos del tamaño de un bocado, polvos Mofilizados y dietas semilíquidas envasadas en tubos de aluminio. La mayoría de los alimentos eran poco apetecibles, los alimentos liofilizados eran difíciles de rehidratar y los polvos en la microgravedad quedaban pegados por las paredes de la nave; desde entonces se han desarrollado múltiples tecnologías y estudios sobre los requerimientos calóricos de los astronautas y conservación de los alimentos.

Abstract The food that NASA's early astronauts ate in space is a testament of their strength. John Glenn, America's first man to eat anything in the near-weightless environment of the Earth's orbit, found the task extremely hard and the menu to be quite limited. Other Mercury astronauts had to base their nutrition on bite-sized cubes, freeze-dried powders and semi-liquids packaged in aluminum tubes. Most of them agreed that the foods were unappetizing and disliked squeezing the tubes. Moreover, freeze-dried foods were hard to rehydrate and the crumbs got stuck on the walls of the spacecraft. Ever since, multiple technologies and studies on the energy requirements of astronauts and food preservation have been developed.

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Resumen: El desarrollo de la investigación encargada de evaluar la adaptación fisiológica del ser humano en el ambiente de ingravidez del espacio está repleto de desafíos especiales. El campo de las ciencias biológicas en condiciones de microgravedad está estrechamente ligado a la exploración del hombre del espacio. Existe una respuesta adaptativa que permite explicar los fenómenos de adaptacion de la fisiologia humana a situaciones de microgravedad, en este trabajo se exponen los cambios mas significativos en respuesta a la adaptación en microgravedad.

Abstract: The development of research responsible for evaluating the physiological adaptation of the human being in the weightless environment of space is filled with challenges. The field of biological sciences in microgravity conditions is closely linked to human exploration of space. There is an adaptive response that helps to explain the phenomena of adaptation of human physiology in microgravity situations, in this work the most significant changes are set in response to the adaptation in microgravity.

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Gravity is the fundamental force that may have operated during the evolution of life on Earth. It is thus important to understand as to what the effects of gravity are on cellular life. The studies related to effect of microgravity on cells may provide greater insights in understanding of how the physical force of gravity shaped life on Earth. The present study focuses on a unique group of organisms called the Haloarchaea, which are known for their extreme resistance to survive in stress-induced environments. The aim of the present investigation was to study the effect of simulated microgravity on physiological response of extremely halophilic archaeon, Haloarcula argentinensis RR10, under slow clinorotation. The growth kinetics of the archaeon in microgravity was studied using the Baryani model and the viable and apoptotic cells were assessed using propidium iodide fluorescent microscopic studies. The physiological mechanism of adaptation was activation of 'salt-in' strategy by intracellular sequestration of sodium ions as detected by EDAX. The organism upregulated the production of ribosomal proteins in simulated microgravity as evidenced by Matrix-assisted laser desorption ionization Time of flight-Mass Spectrophotometry. Simulated microgravity altered the antibiotic susceptibility of the haloarchaeon and it developed resistance to Augmentin, Norfloxacin, Tobramycin and Cefoperazone, rendering it a multidrug resistant strain. The presence of antibiotic efflux pump was detected in the haloarchaeon and it also enhanced production of protective carotenoid pigment in simulated microgravity. The present study is presumably the first report of physiological response of H. argentinensis RR10 in microgravity simulated under slow clinorotation.

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Seeds of a tropical tree species from Brazil, Astronium fraxinifolium, or zebrawood, were germinated, for the first time in microgravity, aboard the International Space Station for nine days. Following three days of subsequent growth under normal terrestrial gravitational conditions, greater root length and numbers of secondary roots was observed in the microgravity-treated seedlings compared to terrestrially germinated controls. Suppression subtractive hybridization of cDNA and EST analysis were used to detect differential gene expression in the microgravity-treated seedlings in comparison to those initially grown in normal gravity (forward subtraction). Despite their return to, and growth in normal gravity, the subtracted library derived from microgravity-treated seedlings was enriched in known microgravity stress-related ESTs, corresponding to large and small heat shock proteins, 14-3-3-like protein, polyubiquitin, and proteins involved in glutathione metabolism. In contrast, the reverse-subtracted library contained a comparatively greater variety of general metabolism-related ESTs, but was also enriched for peroxidase, possibly indicating the suppression of this protein in the microgravity-treated seedlings. Following continued growth for 30 days, higher concentrations of total chlorophyll were detected in the microgravity-exposed seedlings.

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To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis.

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UNLABELLED: The recent engagement of Brazil in the construction and utilization of the International Space Station has motivated several Brazilian research institutions and universities to establish study centers related to Space Sciences. The Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) is no exception. METHOD: The University initiated in 1993 the first degree course training students to operate commercial aircraft in South America (the School of Aeronautical Sciences. A further step was the decision to build the first Brazilian laboratory dedicated to the conduct of experiments in ground-based microgravity simulation. Established in 1998, the Microgravity Laboratory, which was located in the Instituto de Pesquisas Cientificas e Tecnologicas (IPCT), was supported by the Schools of Medicine, Aeronautical Sciences and Electrical Engineering/Biomedical Engineering. At the end of 2006, the Microgravity Laboratory became a Center and was transferred to the School of Engineering. RESULTS: The principal activities of the Microgravity Centre are the development of research projects related to human physiology before, during and after ground-based microgravity simulation and parabolic flights, to aviation medicine in the 21st century and to aerospace biomedical engineering. CONCLUSION: The history of Brazilian, and why not say worldwide, space science should unquestionably go through PUCRS. As time passes, the pioneering spirit of our University in the aerospace area has become undeniable. This is due to the group of professionals, students, technicians and staff in general that have once worked or are still working in the Center of Microgravity, a group of faculty and students that excel in their undeniable technical-scientific qualifications.