Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Simulated microgravity facilitates stomatal ingression by Salmonella in lettuce and suppresses a biocontrol agent.

As human spaceflight increases in duration, cultivation of crops in spaceflight is crucial to protecting human health under microgravity and elevated oxidative stress. Foodborne pathogens (e.g., Salmonella enterica) carried by leafy green vegetables are a significant cause of human disease. Our previous work showed that Salmonella enterica serovar Typhimurium suppresses defensive closure of foliar stomata in lettuce (Lactuca sativa L.) to ingress interior tissues of leaves. While there are no reported occurrences of foodborne disease in spaceflight to date, known foodborne pathogens persist aboard the International Space Station and space-grown lettuce has been colonized by a diverse microbiome including bacterial genera known to contain human pathogens. Interactions between leafy green vegetables and human bacterial pathogens under microgravity conditions present in spaceflight are unknown. Additionally, stomatal dynamics under microgravity conditions need further elucidation. Here, we employ a slow-rotating 2-D clinostat to simulate microgravity upon in-vitro lettuce plants following a foliar inoculation with S. enterica Typhimurium and use confocal microscopy to measure stomatal width in fixed leaf tissue. Our results reveal significant differences in average stomatal aperture width between an unrotated vertical control, plants rotated at 2 revolutions per minute (2 RPM), and 4 RPM, with and without the presence of S. typhimurium. Interestingly, we found stomatal aperture width in the presence of S. typhimurium to be increased under rotation as compared to unrotated inoculated plants. Using confocal Z-stacking, we observed greater average depth of stomatal ingression by S. typhimurium in lettuce under rotation at 4 RPM compared to unrotated and inoculated plants, along with greater in planta populations of S. typhimurium in lettuce rotated at 4 RPM using serial dilution plating of homogenized surface sterilized leaves. Given these findings, we tested the ability of the plant growth-promoting rhizobacteria (PGPR) Bacillus subtilis strain UD1022 to transiently restrict stomatal apertures of lettuce both alone and co-inoculated with S. typhimurium under rotated and unrotated conditions as a means of potentially reducing stomatal ingression by S. typhimurium under simulated microgravity. Surprisingly, rotation at 4 RPM strongly inhibited the ability of UD1022 alone to restrict stomatal apertures and attenuated its efficacy as a biocontrol following co-inoculation with S. typhimurium. Our results highlight potential spaceflight food safety issues unique to production of crops in microgravity conditions and suggest microgravity may dramatically reduce the ability of PGPRs to restrict stomatal apertures.

Discovery of Salidroside as a Novel Non-Coding RNA Modulator to Delay Cellular Senescence and Promote BK-Dependent Apoptosis in Cerebrovascular Smooth Muscle Cells of Simulated Microgravity Rats.

Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague-Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K+ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.

Nicotinamide mononucleotide supplementation mitigates osteopenia induced by modeled microgravity in rats.

Exposure to weightlessness causes severe osteopenia, resulting in raised fracture risk. The current study aimed to investigate whether nicotinamide mononucleotide (NMN) supplementation protected against the osteopenia in hindlimb unloading (HLU) rats in vivo and modeled microgravity-induced osteoblastic dysfunction in vitro. The 3-mo-old rats were exposed to HLU and intragastrically administered NMN every 3 days (500 mg/kg body weight) for 4 weeks. NMN supplementation mitigated HLU-induced bone loss, evidenced by greater bone mass and biomechanical properties and better trabecular bone structure. NMN supplementation mitigated HLU-induced oxidative stress, evidenced by greater levels of nicotinamide adenine dinucleotide and activities of superoxide dismutase 2 and lesser malondialdehyde levels. Modeled microgravity stimulation using rotary wall vessel bioreactor in MC3T3-E1 cells inhibited osteoblast differentiation, which was reversed by NMN treatment. Furthermore, NMN treatment mitigated microgravity-induced mitochondrial impairments, evidenced by lesser reactive oxygen species generation and greater adenosine triphosphate production, mtDNA copy number, and activities of superoxide dismutase 2 and Complex I and II. Additionally, NMN promoted activation of AMP-activated protein kinase (AMPK), evidenced by greater AMPKα phosphorylation. Our research suggested that NMN supplementation attenuated osteoblastic mitochondrial impairment and mitigated osteopenia induced by modeled microgravity.

Microgravity stress alters bacterial community assembly and co-occurrence networks during wheat seed germination.

Bacterial interactions occurring on and around seeds are integral to plant fitness, health and productivity. Although seed- and plant-associated bacteria are sensitive to environmental stress, the effects of microgravity, as present during plant cultivation in space, on microbial assembly during seed germination are not clear. Here, we characterized the bacterial microbiome assembly process and mechanisms during seed germination of two wheat varieties under simulated microgravity by 16S rRNA gene amplicon sequencing and metabolome analysis. We found that the bacterial community diversity, and network complexity and stability were significantly decreased under simulated microgravity. In addition, the effects of simulated microgravity on the plant bacteriome of the two wheat varieties tended to be consistent in seedlings. At this stage, the relative abundance of Oxalobacteraceae, Paenibacillaceae, Xanthomonadaceae, Lachnospiraceae, Sphingomonadaceae and Ruminococcaceae decreased, while the relative abundance of Enterobacteriales increased under simulated microgravity. Analysis of predicted microbial function revealed that simulated microgravity exposure leads to lower sphingolipid signaling and calcium signaling pathways. We also found that simulated microgravity drove the strengthening of deterministic processes in microbial community assembly. Importantly, some specific metabolites exhibited significant changes under simulated microgravity, suggesting that bacteriome assembly is mediated, at least in part, by metabolites altered by microgravity. The data we present here moves us closer to a holistic understanding of the plant bacteriome under microgravity stress at plant emergence, and provides a theoretical basis for the precise utilization of microorganisms in microgravity to improve plant adaptation to the challenge of cultivation in space.

Hawthorn leaves flavonoids attenuate cardiac remodeling induced by simulated microgravity.

CONTEXT: Hawthorn leaves are a kind of widely used medicinal plant in China. The major ingredient, hawthorn leaves flavonoids (HLF), have cardiotonic, cardioprotective, and vascular protective effects. OBJECTIVE: The study evaluated the protective role of HLF in cardiac remodelling and the underlying mechanisms under simulated microgravity by hindlimb unloading rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into control, HLF, HU (hindlimb unloading) and HU + HLF groups (n = 8). After HU and daily intragastric administration at the dose of 100 mg/kg/d for 8 weeks, cardiac function and structure were evaluated by biochemical indices and histopathology. We identified the main active compounds and mechanisms involved in the cardioprotective effects of HLF via bioinformatics and molecular docking analysis, and relative signalling pathway activity was verified by Western blot. RESULTS: HLF treatment could reverse the HU-induced decline in LV-EF (HU, 55.13% ± 0.98% vs. HU + HLF, 71.16% ± 5.08%), LV-FS (HU, 29.44% ± 0.67% vs. HU + HLF, 41.62% ± 4.34%) and LV mass (HU, 667.99 ± 65.69 mg vs. HU + HLF, 840.02 ± 73.00 mg). Furthermore, HLF treatment significantly increased NPRA expression by 135.39%, PKG by 51.27%, decreased PDE5A by 20.03%, NFATc1 by 41.68% and Rcan1.4 by 54.22%. CONCLUSIONS: HLF plays a protective effect on HU-induced cardiac remodelling by enhancing NPRA-cGMP-PKG pathway and suppressing the calcineurin-NFAT pathway, which provides a theoretical basis for use in clinical therapies.

Protective effect of Gastrodia elata blume ameliorates simulated weightlessness-induced cognitive impairment in mice.

During the long-term orbital flight, exposure to microgravity negatively affects the astronauts' development of cognition, characterized by learning and memory decline. Gastrodia elata Blume (GEB) has a significant protective effect on cognitive impairment and has been used in Asia for centuries as a functional product. A previous study demonstrated that GEB could improve memory loss in mice caused by circadian rhythm disorders. However, the effects of GEB on cognitive dysfunction caused by weightless environments have not been investigated. In this study, mice received daily treatment with GEB (0.5, 1 g·kg-1d-1, i.g) and Huperzine A(Hup, 0.1 mg·kg-1d-1, i.g) orally until the end of the behavioral test (New object recognition test (NORT). Malondialdehyde (MDA) and nitric oxide (NO) levels were detected by kits, and expression of brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), phosphorylated Akt (P-AKT), synaptophysin (SYN) and postsynaptic density 95(PSD95) in hippocampus were detected by western blotting. The results show that administration of GEB (0.5, 1 g·kg-1d-1, i.g) and Hup (0.1 mg·kg-1d-1, i.g) remarkably reverse HLS-induced learning and behavioral memory disorders, which were associated with significant changes in MDA and NO levels. Additionally, the protein expressions of BDNF, P-AKT/AKT, SYN, and PSD95 were significantly increased in the hippocampus. In summary, our findings will improve the reference for developing GEB as a functional product that improves memory decline.

The neurology of space flight; How does space flight effect the human nervous system?

RATIONALE AND HYPOTHESIS: Advancements in technology, human adaptability, and funding have increased space exploration and in turn commercial spaceflight. Corporations such as Space X and Blue Origin are exploring methods to make space tourism possible. This could lead to an increase in the number of patients presenting with neurological diseases associated with spaceflight. Therefore, a comprehensive understanding of spaceflight stressors is required to manage neurological disease in high-risk individuals. OBJECTIVES: This review aims to describe the neurological effects of spaceflight and to assess countermeasures such as pre-flight prophylaxis, training, and possible therapeutics to reduce long-term effects. METHODOLOGY: A literature search was performed for experimental studies conducted in astronauts and in animal models that simulated the space environment. Many studies, however, only discussed these with scientific reasoning and did not include any experimental methods. Relevant studies were identified through searching research databases such as PubMed and Google Scholar. No inclusion or exclusion criteria were used. FINDINGS: Analysis of these studies provided a holistic understanding of the acute and chronic neurological changes that occur during space flight. Astronauts are exposed to hazards that include microgravity, cosmic radiation, hypercapnia, isolation, confinement and disrupted circadian rhythms. Microgravity, the absence of a gravitational force, is linked to disturbances in the vestibular system, intracranial and intraocular pressures. Furthermore, microgravity affects near field vision as part of the spaceflight-associated neuro-ocular syndrome. Exposure to cosmic radiation can increase the risk of neurodegenerative conditions and malignancies. It is estimated that cosmic radiation has significantly higher ionising capabilities than the ionising radiation used in medicine. Space travel also has potential benefits to the nervous system, including psychological development and effects on learning and memory. Future work needs to focus on how we can compare a current astronaut to a future space tourist. Potentially the physiological and psychological stresses of space flight might lead to neurological complications in future space travellers that do not have the physiological reserve of current astronauts.

The Characteristic Response of the Human Leukocyte Transcriptome to 60 Days of Bed Rest and to Reambulation.

INTRODUCTION: We sought to isolate the microgravity effect of spaceflight from other space stressors by characterizing the leukocytes' transcriptome of participants to a 60-d bed rest study; an Earth model of microgravity. METHODS: Twenty healthy men received a nutritional supplement or not and 10 blood samples were collected throughout three study phases: baseline data collection (BDC) (BDC-12, BDC-11), head-down tilt (HDT) bed rest (HDT1, HDT2, HDT30, HDT60), and reambulation (R1, R2, R12, R30). We measured gene expression through RNA sequencing of leukocytes, applied generalized linear models to assess differential expression followed by enrichment analysis to identify temporal changes (model 1) and to measure the impact of a nutritional supplement (model 2). RESULTS: Baseline transcriptomes included 14,624 protein-coding transcripts and showed both high intraindividual correlations (mean Kendall coefficient, 0.91 ± 0.04) and interindividual homogeneity (0.89 ± 0.03). We identified 2415 differentially expressed protein-coding transcripts grouping into six clusters (C1-C6). At phase transitions, clusters showed either a decrease-then-increase (C3 and C5) or an increase-then-decrease (C1, C2, C6) pattern. All six clusters converged toward average expression at HDT30 and HDT60. Gene ontology terms at baseline related to immune functions while in bed rest and reambulation related to sequestration of ions, immune response, cellular stress, and mineralization. The nutritional intervention had no effect. CONCLUSIONS: The temporal profiles of leukocytes' transcriptomes emphasized the dynamic nature of gene expression occurring during and after bed rest. Enriched biological processes among the differentially expressed genes included immune related and unrelated responses. The convergence toward no differential expression at days 30 and 60 of bed rest suggests a hypometabolic state. Current findings can guide future work on the complex responses and adaptation mechanisms to microgravity.

Which precocial rodent species is more suitable as the experimental model of microgravity influence on prenatal musculosketal development on international space station?

The International Space Station (ISS) has the possibility to perform experiments regarding rodent reproduction in microgravity. The musculoskeletal system at birth in precocial rodent species more resembles the human than that of altricial rodent species. For precocial rodent species with body weight ≤ 500 g (limit of ISS) determined were: adult body mass, newborn body mass, head-body length, tail length, existing variants (wild, domesticated, laboratory), single/group housing, dry food consumption/24 h, water intake/24 h, basal metabolic rate mlO2/g/h, environmental temperature, sand baths, urine output ml/24 h, fecal output g/24 h, size of fecal droplet, hair length, life span, length of oestrus cycle, duration of pregnancy, building nest, litter size, stage of musculoskeletal maturity at birth, and the duration of weaning. Characteristics were obtained by searching SCOPUS as well as the World Wide Web with key words for each of the species in English, Latin and, local language name. These characteristics were compared in order to find most appropriate species. Twelve precocial rodent species were identified. There is not enough data for Common yellow-toothed cavy, and Eastern spiny mouse. Inappropriate species were: Gundis, Dassie rat are a more demanding species for appropriate tending, litter size is small; Octodon degus requires sand baths as well as a nest during the first two weeks after delivery; muscle maturity of Spiny mouse at birth (myotubular stage), does not correspond to the human (late histochemical stage); Chinchilla requires separately housing, daily sand baths, has upper limit of weight. Possibility of keeping Southern mountain cavy as pet animal, short estrus, large litter size, absence of the need for nest and sand baths, makes this species the most promising candidates for experiments on ISS. If an experiment is planned with exposing gravid animals before term of the birth, then they might be kept together in the existing Rodent Habitat (USA). If an experiment with birth in microgravity is planned on ISS, the existing habitats do not provide conditions for such an experiment. It is necessary to develop habitats for separate keeping of pregnant animals to enable the following: 1. undisturbed delivery 2. prevent the possibility of hurting the newborns 3. ensure adequate post-partum maternal care and nursing.

Research on the Specificity of Electrophysiological Signals of Human Acupoints Based on the 90-Day Simulated Weightlessness Experiment on the Ground.

Acupoint specificity for diseases has consistently been the focus of acupuncture research owing to its excellent prospects for clinical diagnosis and treatment. However, the specificity of cardiovascular and sleep functions in terms of electrical signals at acupoints remains unclear. In this study, five volunteers were recruited and their electrophysiological signals of GV20 (baihui), RN17 (danzhong), PC6 (neiguan), and SP6 (sanyinjiao) and the corresponding sham points, Pittsburgh sleep quality index, blood pressure, and echocardiography were monitored over four periods of 90-day head-down bed rest (HDBR). The results demonstrated that the power and characteristic amplitude of the acupoints were more significant than those of the sham points under normal conditions. And along with the altered physiological condition of the body after HDBR, the differential signal characteristic amplitude (DSCA) and the power of the acupoints were decreased to a larger extent than those of the sham points. In addition, the difference between the power of acupuncture and sham points was also reduced. During the recovery period, except for GV20, the power and DSCA of other acupoints did not return to normal. In terms of DSCA, GV20 is related to human sleep function and other acupoints are related to cardiovascular function. The above results show that the electrophysiological signals of acupoints are disease-specific and more accurately reflect the changes of physiological homeostasis. The research conduces to the development of acupuncture-based disease diagnosis and treatment integrated methods, and the realization of the portable and accurate diagnosis and regulation of diseases in space medicine.

The Effect of Space Travel on Bone Metabolism: Considerations on Today's Major Challenges and Advances in Pharmacology.

Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue homeostasis in microgravity is its capacity to regenerate following fractures due to weakening of the tissue and accidental events during the accomplishment of particularly dangerous tasks. Today, several pharmacological and non-pharmacological countermeasures to this problem have been proposed, including physical exercise, diet supplements and administration of antiresorptive or anabolic drugs. However, each class of pharmacological agents presents several limitations as their prolonged and repeated employment is not exempt from the onset of serious side effects, which limit their use within a well-defined range of time. In this review, we will focus on the various countermeasures currently in place or proposed to address bone loss in conditions of microgravity, analyzing in detail the advantages and disadvantages of each option from a pharmacological point of view. Finally, we take stock of the situation in the currently available literature concerning bone loss and fracture healing processes. We try to understand which are the critical points and challenges that need to be addressed to reach innovative and targeted therapies to be used both in space missions and on Earth.

Aging-like metabolic and adrenal changes in microgravity: State of the art in preparation for Mars.

Endocrine and metabolic changes that typically accompany aging on Earth have been consistently observed in space. Support for the role of gravity in aging has mostly come from ground simulation studies in head down bed rest. However, uncertainties remain and have to be resolved in planning for the ambitious enterprise of sending humans to Mars and back. Stress-related corticosteroid changes and metabolic adaptation to microgravity and their relationship with aging are the object of the present review mostly, albeit of course non exclusively, coming from the personal experience of the authors. The picture coming out of it is that of some, not easily proven, stress-induced cortisol increase accompanied by insulin resistance, both of which represent typical aging-like phenomena mediated by chronic low-grade inflammation. This suggests the need for humans to consider the long journey to safely land, live and work on Mars by taking advantage of integrative medicine solutions including synthetic torpor and/or continuous self-monitoring of eating, sleeping, moving to enable remotely supervised self-treatment.

Sensitivity of Visual System in 5-Day "Dry" Immersion With High-Frequency Electromyostimulation.

The aim of this work was to study the sensitivity of the visual system in 5-day "dry" immersion with a course of high-frequency electromyostimulation (HFEMS) and without it. "Dry" immersion (DI) is one of the most effective models of microgravity. DI reproduces three basic effects of weightlessness: physical inactivity, support withdrawal and elimination of the vertical vascular gradient. The "dry" immersion included in the use of special waterproof and highly elastic fabric on of immersion in a liquid similar in density to the tissues of the human body. The sensitivity of the visual system was assessed by measuring contrast sensitivity and magnitude of the Müller-Lyer illusion. The visual contrast sensitivity was measured in the spatial frequency range from 0.4 to 10.0 cycles/degree. The strength of visual illusion was assessed by means of motor response using "tracking." Measurements were carried out before the start of immersion, on the 1st, 3rd, 5th days of DI, and after its completion. Under conditions of "dry" immersion without HFEMS, upon the transition from gravity to microgravity conditions (BG and DI1) we observed significant differences in contrast sensitivity in the low spatial frequency range, whereas in the experiment with HFEMS-in the medium spatial frequency range. In the experiment without HFEMS, the Müller-Lyer illusion in microgravity conditions was absent, while in the experiment using HFEMS it was significantly above zero at all stages. Thus, we obtained only limited evidence in favor of the hypothesis of a possible compensating effect of HFEMS on changes in visual sensitivity upon the transition from gravity to microgravity conditions and vice versa. The study is a pilot and requires further research on the effect of HFEMS on visual sensitivity.

Nutraceuticals Synergistically Promote Osteogenesis in Cultured 7F2 Osteoblasts and Mitigate Inhibition of Differentiation and Maturation in Simulated Microgravity.

Microgravity is known to impact bone health, similar to mechanical unloading on Earth. In the absence of countermeasures, bone formation and mineral deposition are strongly inhibited in Space. There is an unmet need to identify nutritional countermeasures. Curcumin and carnosic acid are phytonutrients with anticancer, anti-inflammatory, and antioxidative effects and may exhibit osteogenic properties. Zinc is a trace element essential for bone formation. We hypothesized that these nutraceuticals could counteract the microgravity-induced inhibition of osteogenic differentiation and function. To test this hypothesis, we cultured 7F2 murine osteoblasts in simulated microgravity (SMG) in a Random Positioning Machine in the presence and absence of curcumin, carnosic acid, and zinc and evaluated cell proliferation, function, and differentiation. SMG enhanced cell proliferation in osteogenic medium. The nutraceuticals partially reversed the inhibitory effects of SMG on alkaline phosphatase (ALP) activity and did not alter the SMG-induced reduction in the expression of osteogenic marker genes in osteogenic medium, while they promoted osteoblast proliferation and ALP activity in the absence of traditional osteogenic media. We further observed a synergistic effect of the intermix of the phytonutrients on ALP activity. Intermixes of phytonutrients may serve as convenient and effective nutritional countermeasures against bone loss in space.

Long-Term Space Nutrition: A Scoping Review.

This scoping review aimed to identify current evidence and gaps in the field of long-term space nutrition. Specifically, the review targeted critical nutritional needs during long-term manned missions in outer space in addition to the essential components of a sustainable space nutrition system for meeting these needs. The search phrase "space food and the survival of astronauts in long-term missions" was used to collect the initial 5432 articles from seven Chinese and seven English databases. From these articles, two independent reviewers screened titles and abstracts to identify 218 articles for full-text reviews based on three themes and 18 keyword combinations as eligibility criteria. The results suggest that it is possible to address short-term adverse environmental factors and nutritional deficiencies by adopting effective dietary measures, selecting the right types of foods and supplements, and engaging in specific sustainable food production and eating practices. However, to support self-sufficiency during long-term space exploration, the most optimal and sustainable space nutrition systems are likely to be supported primarily by fresh food production, natural unprocessed foods as diets, nutrient recycling of food scraps and cultivation systems, and the establishment of closed-loop biospheres or landscape-based space habitats as long-term life support systems.

Microgravity versus Microgravity and Irradiation: Investigating the Change of Neuroendocrine-Immune System and the Antagonistic Effect of Traditional Chinese Medicine Formula.

During spaceflight, the homeostasis of the living body is threatened with cosmic environment including microgravity and irradiation. Traditional Chinese medicine could ameliorate the internal imbalance during spaceflight, but its mechanism is still unclear. In this article, we compared the difference of neuroendocrine-immune balance between simulated microgravity (S) and simulated microgravity and irradiation (SAI) environment. We also observed the antagonistic effect of SAI using a traditional Chinese medicine formula (TCMF). Wistar rats were, respectively, exposed under S using tail suspending and SAI using tail suspending and 60Co-gama irradiation exposure. The SAI rats were intervened with TCMF. The changes of hypothalamic-pituitary-adrenal (HPA) axis, splenic T-cell, celiac macrophages, and related cytokines were observed after 21 days. Compared with the normal group, the hyperfunction of HPA axis and celiac macrophages, as well as the hypofunction of splenic T-cells, was observed in both the S and SAI group. Compared with the S group, the levels of plasmatic corticotropin-releasing hormone (CRH), macrophage activity, and serous interleukin-6 (IL-6) in the SAI group were significantly reduced. The dysfunctional targets were mostly reversed in the TCMF group. Both S and SAI could lead to NEI imbalance. Irradiation could aggravate the negative feedback inhibition of HPA axis and macrophages caused by S. TCMF could ameliorate the NEI dysfunction caused by SAI.

Gene-Metabolite Network Linked to Inhibited Bioenergetics in Association With Spaceflight-Induced Loss of Male Mouse Quadriceps Muscle.

Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of the National Aeronautics and Space Administration (NASA), we assayed the large-scale mRNA and metabolomic perturbations in the quadriceps of C57BL/6j male mice that lived in spaceflight (FLT) or on the ground (control or CTR) for approximately 4 weeks. The wet weights of the quadriceps were significantly reduced in FLT mice. Next-generation sequencing and untargeted mass spectroscopic assays interrogated the gene-metabolite landscape of the quadriceps. A majority of top-ranked differentially suppressed genes in FLT encoded proteins from the myosin or troponin families, suggesting sarcomere alterations in space. Significantly enriched gene-metabolite networks were found linked to sarcomeric integrity, immune fitness, and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of mitochondrial DNA copy numbers in FLT mice underlined the energy deprivation associated with spaceflight-induced stress. This hypothesis was reinforced by the transcriptomic sequencing-metabolomics integrative analysis that showed inhibited networks related to protein, lipid, and carbohydrate metabolism, and adenosine triphosphate (ATP) synthesis and hydrolysis. Finally, we discovered important upstream regulators, which could be targeted for next-generation therapeutic intervention for chronic disuse of the musculoskeletal system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning-A Systematic Review.

A systematic review was performed to evaluate the effectiveness of nutrition as a standalone countermeasure to ameliorate the physiological adaptations of the musculoskeletal and cardiopulmonary systems associated with prolonged exposure to microgravity. A search strategy was developed to find all astronaut or human space flight bed rest simulation studies that compared individual nutritional countermeasures with non-intervention control groups. This systematic review followed the guidelines of the Cochrane Handbook for Systematic Reviews and tools created by the Aerospace Medicine Systematic Review Group for data extraction, quality assessment of studies and effect size. To ensure adequate reporting this systematic review followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. A structured search was performed to screen for relevant articles. The initial search yielded 4031 studies of which 10 studies were eligible for final inclusion. Overall, the effect of nutritional countermeasure interventions on the investigated outcomes revealed that only one outcome was in favor of the intervention group, whereas six outcomes were in favor of the control group, and 43 outcomes showed no meaningful effect of nutritional countermeasure interventions at all. The main findings of this study were: (1) the heterogeneity of reported outcomes across studies, (2) the inconsistency of the methodology of the included studies (3) an absence of meaningful effects of standalone nutritional countermeasure interventions on musculoskeletal and cardiovascular outcomes, with a tendency towards detrimental effects on specific muscle outcomes associated with power in the lower extremities. This systematic review highlights the limited amount of studies investigating the effect of nutrition as a standalone countermeasure on operationally relevant outcome parameters. Therefore, based on the data available from the included studies in this systematic review, it cannot be expected that nutrition alone will be effective in maintaining musculoskeletal and cardiopulmonary integrity during space flight and bed rest.

The NATO project: nanoparticle-based countermeasures for microgravity-induced osteoporosis.

Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.