In situ study on articular cartilage degeneration in simulated microgravity by HOF-ATR-FTIR spectroscopy.

Fourier transform infrared spectroscopy (FTIRS) can provide rich information on the composition and content of samples, enabling the detection of subtle changes in tissue composition and structure. This study represents the first application of FTIRS to investigate cartilage under microgravity. Simulated microgravity cartilage model was firstly established by tail-suspension (TS) for 7, 14 and 21 days, which would be compared to control samples. A self-developed hollow optical fiber attenuated total reflection (HOF-ATR) probe coupled with a FTIR spectrometer was used for the spectral acquisition of cartilage samples in situ, and one-way analysis of variance (ANOVA) was employed to analyze the changes in the contents of cartilage matrix at different stages. The results indicate that cartilage degenerates in microgravity, the collagen content gradually decreases with the TS time, and the structure of collagen fibers changes. The trends of proteoglycan content and collagen integrity show an initial decrease followed by an increase, ultimately significantly decreasing. The findings provide the basis for the cartilage degeneration in microgravity with TS time, which must be of real significance for space science and health detection.

Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions.

The primary objective of omics in space with focus on the human organism is to characterize and quantify biological factors that alter structure, morphology, function, and dynamics of human cells exposed to microgravity. This review discusses exciting data regarding genomics, transcriptomics, epigenomics, metabolomics, and proteomics of human cells and individuals in space, as well as cells cultured under simulated microgravity. The NASA Twins Study significantly heightened interest in applying omics technologies and bioinformatics in space and terrestrial environments. Here, we present the available publications in this field with a focus on specialized cells and stem cells exposed to real and simulated microgravity conditions. We summarize current knowledge of the following topics: (i) omics studies on stem cells, (ii) omics studies on benign specialized different cell types of the human organism, (iii) discussing the advantages of this knowledge for space commercialization and exploration, and (iv) summarizing the emerging opportunities for translational regenerative medicine for space travelers and human patients on Earth.

Differential Effect of Simulated Microgravity on the Cellular Uptake of Small Molecules.

The space environment can affect the function of all physiological systems, including the properties of cell membranes. Our goal in this study was to explore the effect of simulated microgravity (SMG) on the cellular uptake of small molecules based on reported microgravity-induced changes in membrane properties. SMG was applied to cultured cells using a random-positioning machine for up to three hours. We assessed the cellular accumulation of compounds representing substrates of uptake and efflux transporters, and of compounds not shown to be transported by membrane carriers. Exposure to SMG led to an increase of up to 60% (p < 0.01) in the cellular uptake of efflux transporter substrates, whereas a glucose transporter substrate showed a decrease of 20% (p < 0.05). The uptake of the cathepsin activity-based probe GB123 (MW, 1198 g/mol) was also enhanced (1.3-fold, p < 0.05). Cellular emission of molecules larger than ~3000 g/mol was reduced by up to 50% in SMG (p < 0.05). Our findings suggest that short-term exposure to SMG could differentially affect drug distribution across membranes. Longer exposure to microgravity, e.g., during spaceflight, may have distinct effects on the cellular uptake of small molecules.

The Effect of Short-Term Exposure to Lower Body Positive Pressure on Motor Signal Processing, Reaction Times, and Cardiovascular Parameters in Healthy Volunteers Using Medical Anti-shock Trousers.

Microgravity, as experienced during spaceflight has notable effects on the cognition and cardiovascular systems. However, its effect on motor signal processing is not known. In this study, we planned to study the effect of microgravity simulation with a lower body positive pressure of 50 mmHg on motor signal processing, reaction times, and cardiovascular parameters. Thirty healthy human volunteers participated in this investigation, and continuous ECG and non-invasive blood pressure were measured at baseline, during, and after a lower body positive pressure of 50 mmHg. Bereitschafts potential was recorded at 0 mmHg and 50 mmHg pressure values in a lower body positive pressure (LBPP) suit. Parameters recorded during the pressure change of 0 mmHg to 50 mmHg were RR interval, heart rate, systolic blood pressure, diastolic blood pressure, stroke volume, cardiac output, and peripheral vascular resistance. Heart rate variability (HRV) was calculated from RR intervals during resting and pressure of 50 mm of Hg. We also compared simple and choice reaction times for visual and auditory stimuli during 50 mmHg LBPP exposure with baseline recording. We found a significant increase in systolic blood pressure, stroke volume, and cardiac output from baseline at 50 mmHg of LBPP. We found a significant change in amplitude and area of Bereitschaft potential at the C4 site at 50 mmHg of LBPP. We found a significant change in low-frequency power (LF) as compared to the baseline in HRV. Simple reaction time (visual & auditory) and auditory choice reaction time were improved at 50 mmHg of LBPP. Motor signal processing and reaction time were improved during 50 mmHg of lower body positive pressure exposure.

Exploring New Horizons: Advancements in Cartilage Tissue Engineering Under Space Microgravity.

Novel investigations of how microgravity affects cellular and tissue development have recently been made possible by the multidisciplinary fusion of tissue engineering and space science. This review examines the intersection of cartilage tissue engineering (CTE) and space science, focusing on how microgravity affects cartilage development. Space microgravity induces distinct physiological changes in chondrocytes, including a 20-30% increase in cell diameter, a 1.5- to 2-fold increase in proliferation rates, and up to 3-fold increases in chondrogenic markers such as SOX9 and collagen type II. These cellular alterations impact extracellular matrix composition and tissue structure. Space-optimized bioreactors using dynamic culture methods replicate physiological conditions and enhance tissue growth, but the absence of gravity raises concerns about the mechanical properties of engineered cartilage. Key research areas include the role of growth factors in cartilage development under microgravity, biocompatibility and degradation of scaffold materials in space, and in situ experiments on space stations. This review highlights the opportunities and challenges in leveraging microgravity for CTE advancements, emphasizing the need for continued research to harness space environments for therapeutic applications in cartilage regeneration. The multidisciplinary fusion of tissue engineering and space science opens novel avenues for understanding and improving cartilage tissue engineering, with significant implications for the future of biomedical applications in space and on Earth.

Salidroside alleviates simulated microgravity-induced bone loss by activating the Nrf2/HO-1 pathway.

BACKGROUND: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. METHODS: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. RESULTS: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. CONCLUSION: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage.

Simulated microgravity-induced dysregulation of cerebrospinal fluid immune homeostasis by disrupting the blood-cerebrospinal fluid barrier.

BACKGROUND: The blood-cerebrospinal fluid barrier (BCSFB) comprises the choroid plexus epithelia. It is important for brain development, maintenance, function, and especially for maintaining immune homeostasis in the cerebrospinal fluid (CSF). Although previous studies have shown that the peripheral immune function of the body is impaired upon exposure to microgravity, no studies have reported changes in immune cells and cytokines in the CSF that reflect neuroimmune status. The purpose of this study is to investigate the alterations in cerebrospinal fluid (CSF) immune homeostasis induced by microgravity and its mechanisms. This research is expected to provide basic data for brain protection of astronauts during spaceflight. METHODS: The proportions of immune cells in the CSF and peripheral blood (PB) of SMG rats were analyzed using flow cytometry. Immune function was evaluated by measuring cytokine concentrations using the Luminex method. The histomorphology and ultrastructure of the choroid plexus epithelia were determined. The concentrations of intercellular junction proteins in choroid plexus epithelial cells, including vascular endothelial-cadherin (VE-cadherin), zonula occludens 1 (ZO-1), Claudin-1 and occludin, were detected using western blotting and immunofluorescence staining to characterize BCSFB injury. RESULTS: We found that SMG caused significant changes in the proportion of CD4 and CD8 T cells in the CSF and a significant increase in the levels of cytokines (GRO/KC, IL-18, MCP-1, and RANTES). In the PB, there was a significant decrease in the proportion of T cells and NKT cells and a significant increase in cytokine levels (GRO/KC, IL-18, MCP-1, and TNF-α). Additionally, we observed that the trends in immune markers in the PB and CSF were synchronized within specific SMG durations, suggesting that longer SMG periods (≥21 days) have a more pronounced impact on immune markers. Furthermore, 21d-SMG resulted in ultrastructural disruption and downregulated expression of intercellular junction proteins in rat choroid plexus epithelial cells. CONCLUSIONS: We found that SMG disrupts the BCSFB and affects the CSF immune homeostasis. This study provides new insights into the health protection of astronauts during spaceflight.

Human cranial bone-derived mesenchymal stem cells cultured under simulated microgravity can improve cerebral infarction in rats.

The efficacy of transplanting human cranial bone-derived mesenchymal stem cells (hcMSCs) cultured under simulated microgravity (sMG) conditions has been previously reported; however, their effect on cerebral infarction remains unknown. Here, we examined the efficacy of transplanting hcMSCs cultured in an sMG environment into rat models of cerebral infarction. For evaluating neurological function, hcMSCs cultured in either a normal gravity (1G) or an sMG environment were transplanted in rats 1 day after inducing cerebral infarction. The expression of endogenous neurotrophic, axonal, neuronal, synaptogenic, angiogenic, and apoptosis-related factors in infarcted rat brain tissue was examined using real-time polymerase chain reaction and western blotting 35 days after stroke induction. The RNAs of hcMSCs cultured under 1G or sMG environments were sequenced. The results showed that neurological function was significantly improved after transplantation of hcMSCs from the sMG group compared with that from the 1G group. mRNA expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the sMG group than in the 1G group, whereas sortilin 1 expression was significantly lower. RNA sequencing analysis revealed that genes related to cell proliferation, angiogenesis, neurotrophy, neural and synaptic organization, and inhibition of cell differentiation were significantly upregulated in the sMG group. In contrast, genes promoting microtubule and extracellular matrix formation and cell adhesion, signaling, and differentiation were downregulated. These results demonstrate that hcMSCs cultured in the sMG environment may be a useful source of stem cells for the recovery of neurological function after cerebral infarction.

Microgravity Effect on Pancreatic Islets.

We previously demonstrated that boundary cap neural crest stem cells (BCs) induce the proliferation of beta-cells in vitro, increase survival of pancreatic islets (PIs) in vivo after transplantation, and themselves strongly increase their proliferation capacity after exposure to space conditions. Therefore, we asked if space conditions can induce the proliferation of beta-cells when PIs are alone or together with BCs in free-floating or 3D-printed form. During the MASER 15 sounding rocket experiment, half of the cells were exposed to 6 min of microgravity (µg), whereas another group of cells were kept in 1 g conditions in a centrifuge onboard. The proliferation marker EdU was added to the cells just before the rocket reached µg conditions. The morphological assessment revealed that PIs successfully survived and strongly proliferated, particularly in the free-floating condition, though the fusion of PIs hampered statistical analysis. Proliferation of beta-cells was displayed in 3D-printed islets two weeks after µg exposure, suggesting that the effects of µg may be delayed. Thus, PIs in 3D-printed scaffolds did not fuse, and this preparation is more suitable than free-floating specimens for morphological analysis in µg studies. PIs maintained their increased proliferation capacity for weeks after µg exposure, an effect that may not appear directly, but can emerge after a delay.

Melatonin Regulates Osteoblast Differentiation through the m6A Reader hnRNPA2B1 under Simulated Microgravity.

Recent studies have confirmed that melatonin and N6-methyladenosine (m6A) modification can influence bone cell differentiation and bone formation. Melatonin can also regulate a variety of biological processes through m6A modification. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) serves as a reader of m6A modification. In this study, we used the hindlimb unloading model as an animal model of bone loss induced by simulated microgravity and used 2D clinorotation to simulate a microgravity environment for cells on the ground. We found that hnRNPA2B1 was downregulated both in vitro and in vivo during simulated microgravity. Further investigations showed that hnRNPA2B1 could promote osteoblast differentiation and that overexpression of hnRNPA2B1 attenuated the suppression of osteoblast differentiation induced by simulated microgravity. We also discovered that melatonin could promote the expression of hnRNPA2B1 under simulated microgravity. Moreover, we found that promotion of osteoblast differentiation by melatonin was partially dependent on hnRNPA2B1. Therefore, this research revealed, for the first time, the role of the melatonin/hnRNPA2B1 axis in osteoblast differentiation under simulated microgravity. Targeting this axis may be a potential protective strategy against microgravity-induced bone loss and osteoporosis.

Feasibility of ultrasound-guided nerve blocks in simulated microgravity: a proof-of-concept study for regional anaesthesia during deep space missions.

BACKGROUND: With crewed deep space exploration on the horizon, preparation for potential astronaut health crises in space missions has become vital. Administration of anaesthesia and analgesia presents many challenges owing to constraints specific to space (physiologic and ergonomic challenges associated with microgravity) and nonspecific factors (isolation and lack of supplies). Regional anaesthesia can be the safest option; however, we hypothesised that the ergonomics of microgravity would compromise ease and accuracy of nerve blocks. METHODS: We evaluated the feasibility of regional anaesthesia in a simulated microgravity environment (free-floating underwater conditions) using a meat (bovine muscle) model. Forty meat models were randomised for injection under simulated microgravity or normal gravity conditions. Success rates were determined by blinded assessors after injection. Parameters assessed included time to block, ease of image acquisition, and ease of needle placement. RESULTS: The median time to block in normal gravity was 27 (interquartile range 21-69) s vs 35 (interquartile range 22-48) s in simulated microgravity (P=0.751). Ease of image acquisition was similar in both conditions, as was ease of needle placement. There was no significant difference in the rate of accidental intraneural injections (5% vs 5%), with block success rates comparable in both scenarios (80% normal gravity vs 85% microgravity, P>0.999). CONCLUSIONS: Regional anaesthesia appears feasible for experts in simulated microgravity despite the ergonomic challenges. Although our model has limitations and might not fully capture the complexities of actual space conditions, it provides a foundation for future research into anaesthesia and analgesia during deep space missions.

Spirulina platensis components mitigate bone density loss induced by simulated microgravity: A mechanistic insight.

In microgravity conditions, the consumption of Spirulina platensis (SP) as a renewable food source shows promise in mitigating osteoporosis due to its high nutritional content photosynthetic efficiency, environmental adaptability and positive effects on bone density, though the exact bioactive components and mechanisms remain unclear. Using a hindlimb suspension (HLS) model, this study investigated SP components: proteins (SPP), polysaccharides (SPS), lipids (SPL), and residue (SPR) on bone density and metabolism. Findings revealed that SPP and SPS significantly enhanced bone density and reduced oxidative stress. Activation of the FoxO3/Wnt/ß-catenin pathway reduced FoxO3a expression and increased Wnt signaling molecules and ß-catenin protein, boosting bone formation. Moreover, these components promoted beneficial gut bacteria like Turicibacter, reduced the Firmicutes-to-Bacteroidetes ratio, and enhanced SCFAs production, crucial for bone health. This study emphasized the potential of Spirulina nutrients in addressing space-induced osteoporosis and developing functional foods for long-term space missions.

Spaceflight-induced contractile and mitochondrial dysfunction in an automated heart-on-a-chip platform.

With current plans for manned missions to Mars and beyond, the need to better understand, prevent, and counteract the harmful effects of long-duration spaceflight on the body is becoming increasingly important. In this study, an automated heart-on-a-chip platform was flown to the International Space Station on a 1-mo mission during which contractile cardiac function was monitored in real-time. Upon return to Earth, engineered human heart tissues (EHTs) were further analyzed with ultrastructural imaging and RNA sequencing to investigate the impact of prolonged microgravity on cardiomyocyte function and health. Spaceflight EHTs exhibited significantly reduced twitch forces, increased incidences of arrhythmias, and increased signs of sarcomere disruption and mitochondrial damage. Transcriptomic analyses showed an up-regulation of genes and pathways associated with metabolic disorders, heart failure, oxidative stress, and inflammation, while genes related to contractility and calcium signaling showed significant down-regulation. Finally, in silico modeling revealed a potential link between oxidative stress and mitochondrial dysfunction that corresponded with RNA sequencing results. This represents an in vitro model to faithfully reproduce the adverse effects of spaceflight on three-dimensional (3D)-engineered heart tissue.

Exploring the potential of plant astrobiology: adapting flora for extra-terrestrial habitats: a review.

In recent years, the realm of astrobiology has expanded beyond the search for microbial life to encompass the intriguing possibility of plant life beyond our planet. Plant astrobiology delves into the adaptations and mechanisms that might allow Earth's flora to flourish in the harsh conditions of outer space and other celestial bodies. This review aims to shed light on the captivating field of plant astrobiology, its implications, and the challenges and opportunities it presents. Plant astrobiology marries the disciplines of botany and astrobiology, challenging us to envision the growth of plants beyond Earth's atmosphere. Researchers in this field are not only exploring the potential for plant life on other planets and moons but also investigating how plants could be harnessed to sustain life during extended space missions. The review discusses how plants could adapt to environments characterized by low gravity, high radiation, extreme temperature fluctuations, and different atmospheric compositions. It highlights the physiological changes necessary for plants to survive and reproduce in these conditions. A pivotal concept is the integration of plants into closed-loop life support systems, where plants would play a crucial role in recycling waste products, generating oxygen, and producing food. The review delves into ongoing research involving genetic modifications and synthetic biology techniques to enhance plants' resilience in space environments. It addresses ethical considerations associated with altering organisms for off-planet habitation. Additionally, the review contemplates the psychological and emotional benefits of having greenery in enclosed, isolated space habitats. The review concludes that by employing advanced research methodologies, the field of plant astrobiology can greatly enhance the viability and sustainability of future space missions, highlighting the essential role of plants in sustaining long-term human presence beyond Earth.

Differential Functional Changes in Visual Performance during Acute Exposure to Microgravity Analogue and Their Potential Links with Spaceflight-Associated Neuro-Ocular Syndrome.

BACKGROUND: Spaceflight-Associated Neuro-Ocular Syndrome (SANS) is a complex pathology threatening the health of astronauts, with incompletely understood causes and no current specific functional diagnostic or screening test. We investigated the use of the differential performance of the visual system (central vs. perimacular visual function) as a candidate marker of SANS-related pathology in a ground-based microgravity analogue. METHODS: We used a simple reaction time (SRT) task to visual stimuli, presented in the central and perimacular field of view, as a measure of the overall performance of the visual function, during acute settings (first 10 min) of vertical, bed rest (BR), -6°, and -15° head-down tilt (HDT) presentations in healthy participants (n = 8). We built dose-response models linking the gravitational component to SRT distribution parameters in the central vs. perimacular areas. RESULTS: Acute exposure to microgravity induces detectable changes between SRT distributions in the perimacular vs. central retina (increased mean, standard deviation, and tau component of the ex-Gaussian function) in HDT compared with vertical presentation. CONCLUSIONS: Functional testing of the perimacular retina might be beneficial for the earlier detection of SANS-related ailments in addition to regular testing of the central vision. Future diagnostic tests should consider the investigation of the extra-macular areas, particularly towards the optic disc.

Smile Beyond the Stars: A Narrative Review Exploring the Challenges for Dentistry in Space.

Space dentistry addresses the unique challenges of providing dental care in space, where zero gravity, limited resources, and the vast distance from Earth complicate the maintenance of oral health. Ensuring astronauts' dental health is crucial, as dental issues can adversely affect their overall health and mission performance. Microgravity exacerbates risks for dental problems such as periodontitis, dental caries, bone loss, and potentially, neoplasms. Traditional dental care methods become less effective in microgravity, leading to increased plaque accumulation and worsening of dental diseases. As space missions venture further and last longer, maintaining oral hygiene presents unique challenges that necessitate innovative solutions. These include specialized tools like ergonomic toothbrushes and 3D-printed dental prostheses designed to function effectively in a zero-gravity environment. Preventive measures, such as comprehensive astronaut training programs focusing on oral health, are vital. These programs educate astronauts on maintaining oral hygiene and managing potential dental issues using available resources. Collaborative efforts among dental professionals, engineers, and space agencies are essential to developing comprehensive strategies for space dentistry. Such interdisciplinary collaboration leads to the advancement of dental care technologies and methodologies that can address the unique needs of astronauts. Despite the formidable challenges, these innovative solutions and collaborative efforts offer promising avenues for ensuring the dental health of astronauts during long-duration missions. This review aims to examine the detrimental effects of microgravity on the oral cavity and explore potential solutions to these issues, ensuring that humanity can continue to push the boundaries of space exploration while safeguarding the well-being of those who venture into the cosmos.

Effects of simulated space conditions on CD4+ T cells: a multi modal analysis.

Introduction: The immune system is an intricate network of cellular components that safeguards against pathogens and aberrant cells, with CD4+ T cells playing a central role in this process. Human space travel presents unique health challenges, such as heavy ion ionizing radiation, microgravity, and psychological stress, which can collectively impede immune function. The aim of this research was to examine the consequences of simulated space stressors on CD4+ T cell activation, cytokine production, and gene expression. Methods: CD4+ T cells were obtained from healthy individuals and subjected to Fe ion particle radiation, Photon irradiation, simulated microgravity, and hydrocortisone, either individually or in different combinations. Cytokine levels for Th1 and Th2 cells were determined using multiplex Luminex assays, and RNA sequencing was used to investigate gene expression patterns and identify essential genes and pathways impacted by these stressors. Results: Simulated microgravity exposure resulted in an apparent Th1 to Th2 shift, evidenced on the level of cytokine secretion as well as altered gene expression. RNA sequencing analysis showed that several gene pathways were altered, particularly in response to Fe ions irradiation and simulated microgravity exposures. Individually, each space stressor caused differential gene expression, while the combination of stressors revealed complex interactions. Discussion: The research findings underscore the substantial influence of the space exposome on immune function, particularly in the regulation of T cell responses. Future work should focus expanding the limited knowledge in this field. Comprehending these modifications will be essential for devising effective strategies to safeguard the health of astronauts during extended space missions. Conclusion: The effects of simulated space stressors on CD4+ T cell function are substantial, implying that space travel poses a potential threat to immune health. Additional research is necessary to investigate the intricate relationship between space stressors and to develop effective countermeasures to mitigate these consequences.

Artificial Gravity: An Effective Countermeasure for Microgravity-Induced Headward Fluid Shift?

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine if daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of six-degree head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: No AG (control), daily 30-minute intermittent AG (iAG), and daily 30-minute continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA flow rate (ICAFR), aqueductal cerebral spinal fluid flow velocity (CSFV), and intracranial volumetrics were quantified at 3T. MRI was performed at baseline, 14 and 52 days into HDTBR, and three days after HDTBR(recovery). A mixed model approach was used with intervention and time as the fixed effect factors and the subject as the random effect factor. Compared to baseline, HDTBR was characterized by expansion of lateral ventricular, white matter, gray matter, and brain + total intracranial cerebral spinal fluid volumes, increased CSFv, decreased ICASV, and decreased ICAFR by 52 days into HBTBR (All Ps <0.05). ICARI was only increased 14 days into HDTBR (P <0.05). Neither iAG nor cAG significantly affected measurements compared to HDTBR alone, indicating that thirty minutes of daily exposure was insufficient to mitigate the intracranial effects of headward fluid shift. Greater AG session exposure time, gravitational force or both are suggested for future countermeasure research.

Mesenchymal stem cells arouse myocardial NAD+ metabolism to alleviate microgravity-induced cardiac dysfunction.

After prolonged space operations, astronauts showed maladaptive atrophy within mostly left-ventricular myocardium, resulting in cardiac dysfunction. However, the mechanism of cardiac dysfunction under microgravity conditions is unclear, and the relevant prevention and treatment measures also need to be explored. Through simulating the microgravity environment with a tail suspension (TS) model, we found that long-term exposure to microgravity promotes aging of mouse hearts, which is closely related to cardiac dysfunction. The intravenous administration of adipose-derived mesenchymal stem cells (ADSCs) emerged preventive and therapeutic effect against myocardial senescence and the decline in cardiac function. Plasma metabolomics analysis suggests the loss of NAD+ in TS mice and motivated myocardial NAD + metabolism and utilization in ADSCs-treated mice, likely accounting for ADSCs' function. Oral administration of nicotinamide mononucleotide (NMN, a NAD + precursor) showed similar therapeutic effect to ADSCs treatment. Collectively, these data implicate the effect of ADSCs in microgravity-induced cardiac dysfunction and provide new therapeutic ideas for aging-related maladaptive cardiac remodeling.

Otoacoustic Estimate of Astronauts' Intracranial Pressure Changes During Spaceflight.

PURPOSE: To investigate the potential correlation between prolonged exposure to microgravity on the International Space Station and increased intracranial fluid pressure, which is considered a risk factor for the astronauts' vision, and to explore the feasibility of using distortion product otoacoustic emissions as a non-invasive in-flight monitor for intracranial pressure changes. METHODS: Distortion product otoacoustic emission phase measurements were taken from both ears of five astronauts pre-flight, in-flight, and post-flight. These measurements served as indirect indicators of intracranial pressure changes, given their high sensitivity to middle ear transmission alterations. The baseline pre-flight ground measurements were taken in the seated upright position. RESULTS: In-flight measurements revealed a significant systematic increase in otoacoustic phase, indicating elevated intracranial pressure during spaceflight compared to seated upright pre-flight ground baseline. Noteworthy, in two astronauts, strong agreement was also observed between the time course of the phase changes measured in the two ears during and after the mission. Reproducibility and stability of the probe placement in the ear canal were recognized as a critical issue. CONCLUSIONS: The study suggests that distortion product otoacoustic emissions hold promise as a non-invasive tool for monitoring intracranial pressure changes in astronauts during space missions. Pre-flight measurements in different body postures and probe fitting strategies based on the individual ear morphology are needed to validate and refine this approach.