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.

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.

BACKGROUND: Cardiopulmonary resuscitation (CPR) in microgravity requires specific methods to counteract weightlessness. Automatic chest compression devices (ACCDs) could improve CPR in microgravity. We aimed to compare ACCDs versus manual CPR in microgravity simulated through parabolic flights.
METHODS: This prospective, open, controlled study compared 3 ACCDs (LUCAS 3©, AUTOPULSE©, EASYPULSE©) to manual CPR during the 66th CNES (Centre National d\'Etudes Spatiales) parabolic flights campaign onboard the Novespace Air Zero-G A310 aircraft. Chest compression depths and rates were monitored by a Laerdal© Resusci-Ann-QCPR manikin.
RESULTS: The LUCAS 3© device had a median compression depth of 53.0 [53.0 - 54.0] mm, significantly higher than the EASYPULSE©, AUTOPULSE©, and Manual CPR (Handstand method), measured at 29.0 [26.0 - 32.0] mm, 29.0 [27.5 - 30.7] mm and 34.5 [29.6 - 43.3] mm, respectively (p value <0.001). Compression rates were 101 [101 - 101], 100 [100 - 100] and 80 [80 - 80] compressions per minute (cpm) for the LUCAS 3©, EASYPULSE©, and AUTOPULSE©, respectively. Manual CPR provided a significantly higher compression rate with 115 [109 - 123] cpm (p value <0.001).
CONCLUSIONS: Only LUCAS 3© provided effective CPR according to international guidelines. ACCDs should implement microgravity CPR algorithms.

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.

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long-Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space.

Changes in the structure of bone can occur in space as an adaptive response to microgravity and on Earth due to the adaptive effects to exercise, to the aging of bone cells, or to prolonged disuse. Knowledge of cell-mediated bone remodeling on Earth informs our understanding of bone tissue changes in space and whether these skeletal changes might increase the risk for fractures or premature osteoporosis in astronauts. Comparisons of skeletal health between astronauts and aging humans, however, may be both informative and misleading. Astronauts are screened for a high level of physical fitness and health, are launched with high bone mineral densities, and perform exercise daily in space to combat skeletal atrophy as an adaptive response to reduced weight-bearing function, while the elderly display cellular and tissue pathology as a response to senescence and disuse. Current clinical testing for age-related bone change, applied to astronauts, may not be sufficient for fully understanding risks associated with rare and uniquely induced bone changes. This review aims to (i) highlight cellular analogies between spaceflight-induced and age-related bone loss, which could aid in predicting fractures, (ii) discuss why overreliance on terrestrial clinical approaches may miss potentially irreversible disruptions in trabecular bone microarchitecture induced by spaceflight, and (iii) detail how the cellular effects of the bisphosphonate class of drugs offer a prophylactic countermeasure for suppressing the elevated bone resorption characteristically observed during long-duration spaceflights. Thus the use of the bisphosphonate will help protect the bone from structural changes while in microgravity either along with exercise or alone when exercise is not performed, e.g. after an injury or illness.

UNASSIGNED: The risk of skin injuries in space is increasing with longer space missions and a growing astronaut population. This highlights the importance of understanding the adverse effects of weightlessness on wound healing. The objective of this research was to examine the therapeutic potential of Low-Level Light Therapy (LLLT) on skin healing processes under simulated microgravity (SMG) conditions and uncover the underlying molecular mechanisms, thus providing innovative solutions and a sound theoretical basis for space skin injuries.
UNASSIGNED: Hindlimb unloading (HU) mice models were used to simulate weightlessness conditions, with or without a complete management of LLLT for 14 days. A systematic testing consisting of HE, Masson and immunohistochemical staining was performed against the standardized mouse tissue specimens. In vitro assessment of cellular biological functions under SMG conditions was carried out in the rotation system of culture (RSOC) using HaCaT and NIH3T3 cell-lines.
UNASSIGNED: Under SMG conditions, LLLT significantly reduced skin wound area in HU mice, especially on Days 10 (p < 0.001), accompanied by increased collagen deposition and elevated levels of Ki67 and CD31. Moreover, LLLT showed impressive anti-inflammatory effects represented by the reduced in pro-inflammatory markers including LY6G, F4/80 and CD86, as well as the decreased levels of IL-1β, IL-6 and TNF-α. Conversely, an elevation in the anti-inflammatory marker CD206 was observed. By employing bioinformatics technology, we further found the PI3K/AKT signaling was prominent in the KEGG pathway analysis and CCR2 acted as a hub gene in the interaction network. Therefore, we demonstrated that LLLT could enhance the phosphorylation of PI3K/AKT and reduce CCR2 expression under SMG conditions, while CCR2 knockdown promoted the phosphorylation of PI3K/AKT, suggesting an important role of CCR2/PI3K/AKT signal axis in LLLT-accelerated wound healing under SMG conditions.
UNASSIGNED: LLLT induced activation of the PI3K/AKT signaling pathway through suppression of CCR2 expression, which significantly enhanced skin wound healing under SMG conditions.s.

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.

Pseudomonas aeruginosa forms aggregates known as biofilms. Previous studies have shown that when P. aeruginosa is cultivated in space, thicker and structurally different biofilms are formed than from those grown on Earth. We investigated how microgravity, simulated in a laboratory setting, influenced the growth, colonization, and virulence potentials of a P. aeruginosa PA14 wild-type strain, as well as two surface attachment-defective (sad) mutants altered at crucial biofilm-forming steps: flgK and pelA. Using high-aspect ratio rotating-wall vessel (HARV) bioreactors, P. aeruginosa bacteria were grown to stationary phase under prolonged (6 days) exposure to simulated microgravity or normal gravity conditions. After the exposure, the capacity of the culture to form biofilms was measured. Additionally, pigment (pyocyanin) formed by each culture during the incubation was extracted and quantified. We demonstrate that the first prolonged exposure to low-shear modeled microgravity (LSMMG) and without nutrient replenishment significantly diminishes wild-type P. aeruginosa PA14 biofilm formation abilities after exposure and pyocyanin production during exposure, while the mutant strains exhibit differing outcomes for both properties.
OBJECTIVE: Given plans for humans to engage in prolonged space travel, we investigated biofilm and pigment/virulence factor formation in Pseudomonas aeruginosa when cultivated in microgravity. These bacteria are opportunistic pathogens in immunocompromised individuals. Previous studies of space travelers have shown some immune system diminutions. Hence, our studies shed some light on how prolonged cultivation of bacteria in simulated microgravity conditions affect their growth characteristics.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.