Статті в журналах: "Microgravity effects"

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SON, HOANG NGHIA, HO NGUYEN QUYNH CHI, LE NGOC PHUONG THANH, TRUONG THI HAN, NGUYEN THAI MINH HAN, DOAN CHINH CHUNG, and LE THANH LONG. "Effects of simulated microgravity on the morphology of mouse embryonic fibroblasts (MEFs)." Romanian Biotechnological Letters 25, no. 6 (October 18, 2020): 2156–60. http://dx.doi.org/10.25083/rbl/25.6/2156.2160.

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This study aimed to assess the effects of simulated microgravity on mouse embryonic fibroblast (MEF) morphology. The results showed that the area of MEFs under simulated microgravity was 7843.39 ± 551.31 µm2 which was lower than the control group (9832.72 ± 453.86 µm2). The nuclear area of MEFs under simulated microgravity (290.76 ± 4.58 µm2) and the control group (296.8 ± 4.58 µm2) did not statistically differ. In addition, the nuclear shape value of the MEFs under simulated microgravity and the control group did not statistically differ (0.86 ± 0.006 vs. 0.87 ± 0.003, respectively). The nuclear intensity of MEFs under simulated microgravity (19361 ± 852) was higher than the control group (16997 ± 285). Moreover, the flow cytometry analysis indicated the reduced G0/G1 phase cell ratio and the increased S phase and G2/M phase cell ratio in MEFs under simulated microgravity. Simulated microgravity also induced a decrease in diameter of actin filament bundles of the MEFs under simulated microgravity (1.61 ± 0.33 µm) compared to the control group (1.79 ± 0.32 µm). These results revealed that simulated microgravity is capable of inducing the morphological changes of mouse embryonic fibroblasts.

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Ludtka, Christopher, Erika Moore, and Josephine B. Allen. "The Effects of Simulated Microgravity on Macrophage Phenotype." Biomedicines 9, no. 9 (September 12, 2021): 1205. http://dx.doi.org/10.3390/biomedicines9091205.

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The effects of spaceflight, including prolonged exposure to microgravity, can have significant effects on the immune system and human health. Altered immune cell function can lead to adverse health events, though precisely how and to what extent a microgravity environment impacts these cells remains uncertain. Macrophages, a key immune cell, effect the inflammatory response as well as tissue remodeling and repair. Specifically, macrophage function can be dictated by phenotype that can exist between spectrums of M0 macrophage: the classically activated, pro-inflammatory M1, and the alternatively activated, pro-healing M2 phenotypes. This work assesses the effects of simulated microgravity via clinorotation on M0, M1, and M2 macrophage phenotypes. We focus on phenotypic, inflammatory, and angiogenic gene and protein expression. Our results show that across all three phenotypes, microgravity results in a decrease in TNF-α expression and an increase in IL-12 and VEGF expression. IL-10 was also significantly increased in M1 and M2, but not M0 macrophages. The phenotypic cytokine expression profiles observed may be related to specific gravisensitive signal transduction pathways previously implicated in microgravity regulation of macrophage gene and protein expression. Our results highlight the far-reaching effects that simulated microgravity has on macrophage function and provides insight into macrophage phenotypic function in microgravity.

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Xu, Dongqian, Shuangsheng Guo, and Min Liu. "Effects of long-term simulated microgravity on tomato seedlings." Canadian Journal of Plant Science 94, no. 2 (March 2014): 273–80. http://dx.doi.org/10.4141/cjps2013-063.

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Xu, D., Guo, S. and Liu, M. 2014. Effects of long-term simulated microgravity on tomato seedlings. Can. J. Plant Sci. 94: 273–280. Whether plants can adapt to a long-term microgravity environment is crucial to their reproduction in bioregenerative life-support systems in space. This research investigated the effects of simulated microgravity on Lycopersivon esculentum Mill. (cv. Dwarf Red-bell). Several indicators, namely germination ratio, percentage of cell membrane damage, malondialdehyde content (MDA), superoxide anion ([Formula: see text]) content, and mininucleolus, were observed 10, 20, 30, and 40 d after planting (DAP). Simulated microgravity [random positioning machine (RPM) treatment] barely had any effect on germination ratio, but it increased MDA, an index indicating membrane lipid peroxidation. Random positioning machine-treated samples had significantly higher [Formula: see text] content until 16 DAP, but these differences ceased after 21 DAP. Simulated microgravity damaged cell membranes, and the damage severity was positively related to the duration of the simulated microgravity treatment. Mininucleoli were more common in RPM-treated root tips than in the 1×g ones. In conclusion, simulated microgravity seriously disturbed tomato seedling growth by damaging cell membrane integrity, causing the accumulation of hazardous substances, and affecting the cell nucleus structure.

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Prasanth, Devika, Sindhuja Suresh, Sruti Prathivadhi-Bhayankaram, Michael Mimlitz, Noah Zetocha, Bong Lee, and Andrew Ekpenyong. "Microgravity Modulates Effects of Chemotherapeutic Drugs on Cancer Cell Migration." Life 10, no. 9 (August 24, 2020): 162. http://dx.doi.org/10.3390/life10090162.

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Microgravity or the condition of apparent weightlessness causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. These organ and system-level dysfunctions correlate with changes induced at the single cell level both by simulated microgravity on earth as well as microgravity conditions in outer space (as in the international space station). Reported changes in single bone cells, muscle cells and white blood cells include structural/morphological abnormalities, changes in gene expression, protein expression, metabolic pathways and signaling pathways, suggesting that cells mount some response or adjustment to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear largely because the primary mechanism of gravity sensing in animal cells is unknown. Here, we used a rotary cell culture system developed by NASA to subject leukemic and erythroleukemic cancer cells to microgravity for 48 h and then quantified their innate immune response to common anti-cancer drugs using biophysical parameters and our recently developed quantum-dot-based fluorescence spectroscopy. We found that leukemic cancer cells treated with daunorubicin show increased chemotactic migration (p < 0.01) following simulated microgravity (µg) compared to normal gravity on earth (1 g). However, cells treated with doxorubicin showed enhanced migration both in 1 g and following µg. Our results show that microgravity modulates cancer cell response to chemotherapy in a drug-dependent manner. These results suggest using simulated microgravity as an immunomodulatory tool for the development of new immunotherapies for both space and terrestrial medicine.

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Morabito, Caterina, Simone Guarnieri, Alessandra Cucina, Mariano Bizzarri, and Maria A. Mariggiò. "Antioxidant Strategy to Prevent Simulated Microgravity-Induced Effects on Bone Osteoblasts." International Journal of Molecular Sciences 21, no. 10 (May 21, 2020): 3638. http://dx.doi.org/10.3390/ijms21103638.

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The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 osteoblast cells, cellular morphology, proliferation, and metabolism were investigated during exposure to simulated microgravity on a random positioning machine in the absence or presence of an antioxidant—the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our results confirm that simulated microgravity-induced morphological and metabolic alterations characterized by increased levels of reactive oxygen species and a slowdown of the proliferative rate. Interestingly, the use of Trolox inhibited the simulated microgravity-induced effects. Indeed, the antioxidant-neutralizing oxidants preserved cell cytoskeletal architecture and restored cell proliferation rate and metabolism. The use of appropriate antioxidant countermeasures could prevent the modifications and damage induced by microgravity on osteoblastic cells and consequently on bone homeostasis.

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Watenpaugh, Donald E., Jay C. Buckey, Lynda D. Lane, F. Andrew Gaffney, Benjamin D. Levine, Willie E. Moore, Sheryl J. Wright, and C. Gunnar Blomqvist. "Effects of spaceflight on human calf hemodynamics." Journal of Applied Physiology 90, no. 4 (April 1, 2001): 1552–58. http://dx.doi.org/10.1152/jappl.2001.90.4.1552.

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Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 ± 0.16 ml · 100 ml−1 · min−1) relative to 1-G supine conditions (1.94 ± 0.19 ml · 100 ml−1 · min−1, P = 0.01), and arterial pressure tended to increase ( P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 ± 4 units; in-flight: 83 ± 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight ( P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the “upright set-point” hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.

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Buravkova, Ludmila, Irina Larina, Elena Andreeva, and Anatoly Grigoriev. "Microgravity Effects on the Matrisome." Cells 10, no. 9 (August 27, 2021): 2226. http://dx.doi.org/10.3390/cells10092226.

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Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the “gravisensors” in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity. This review covers the current understanding of ECM and associated molecules as the matrisome, the features of the above components in connective tissues, and the role of the latter in the cell and tissue responses to the gravity alterations. Special attention is paid to contemporary methodological approaches to the matrisome composition analysis under real space flights and ground-based simulation of its effects on Earth.

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Kiefer, J., and H. D. Pross. "Space radiation effects and microgravity." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 430, no. 2 (December 1999): 299–305. http://dx.doi.org/10.1016/s0027-5107(99)00142-6.

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Anderson, Allison P., Jacob G. Swan, Scott D. Phillips, Darin A. Knaus, Nicholas T. Kattamis, Christine M. Toutain-Kidd, Michael E. Zegans, Abigail M. Fellows, and Jay C. Buckey. "Acute effects of changes to the gravitational vector on the eye." Journal of Applied Physiology 120, no. 8 (April 15, 2016): 939–46. http://dx.doi.org/10.1152/japplphysiol.00730.2015.

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Intraocular pressure (IOP) initially increases when an individual enters microgravity compared with baseline values when an individual is in a seated position. This has been attributed to a headward fluid shift that increases venous pressures in the head. The change in IOP exceeds changes measured immediately after moving from seated to supine postures on Earth, when a similar fluid shift is produced. Furthermore, central venous and cerebrospinal fluid pressures are at or below supine position levels when measured initially upon entering microgravity, unlike when moving from seated to supine postures on Earth, when these pressures increase. To investigate the effects of altering gravitational forces on the eye, we made ocular measurements on 24 subjects (13 men, 11 women) in the seated, supine, and prone positions in the laboratory, and upon entering microgravity during parabolic flight. IOP in microgravity (16.3 ± 2.7 mmHg) was significantly elevated above values in the seated (11.5 ± 2.0 mmHg) and supine (13.7 ± 3.0 mmHg) positions, and was significantly less than pressure in the prone position (20.3 ± 2.6 mmHg). In all measurements, P < 0.001. Choroidal area was significantly increased in subjects in a microgravity environment ( P < 0.007) compared with values from subjects in seated (increase of 0.09 ± 0.1 mm2) and supine (increase of 0.06 ± 0.09 mm2) positions. IOP results are consistent with the hypothesis that hydrostatic gradients affect IOP, and may explain how IOP can increase beyond supine values in microgravity when central venous and intracranial pressure do not. Understanding gravitational effects on the eye may help develop hypotheses for how microgravity-induced visual changes develop.

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Ruden, Douglas M., Alan Bolnick, Awoniyi Awonuga, Mohammed Abdulhasan, Gloria Perez, Elizabeth E. Puscheck, and Daniel A. Rappolee. "Effects of Gravity, Microgravity or Microgravity Simulation on Early Mammalian Development." Stem Cells and Development 27, no. 18 (September 15, 2018): 1230–36. http://dx.doi.org/10.1089/scd.2018.0024.

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Wang, Mei, Jinxia Li, Shunyu Zhang, Yue You, Xianyu Zhu, Huandong Xiang, Liang Yan, Feng Zhao, and Yunhui Li. "Effects of Titanium Dioxide Nanoparticles on Cell Growth and Migration of A549 Cells under Simulated Microgravity." Nanomaterials 12, no. 11 (May 31, 2022): 1879. http://dx.doi.org/10.3390/nano12111879.

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With the increasing application of nanomaterials in aerospace technology, the long-term space exposure to nanomaterials especially in the space full of radiation coupled with microgravity condition has aroused great health concerns of the astronauts. However, few studies have been conducted to assess these effects, which are crucial for seeking the possible intervention strategy. Herein, using a random positioning machine (RPM) to simulate microgravity, we investigated the behaviors of cells under simulated microgravity and also evaluated the possible toxicity of titanium dioxide nanoparticles (TiO2 NPs), a multifunctional nanomaterial with potential application in aerospace. Pulmonary epithelial cells A549 were exposed to normal gravity (1 g) and simulated gravity (~10−3 g), respectively. The results showed that simulated microgravity had no significant effect on the viability of A549 cells as compared with normal gravity within 48 h. The effects of TiO2 NPs exposure on cell viability and apoptosis were marginal with only a slightly decrease in cell viability and a subtle increase in apoptosis rate observed at a high concentration of TiO2 NPs (100 μg/mL). However, it was observed that the exposure to simulated microgravity could obviously reduce A549 cell migration compared with normal gravity. The disruption of F-actin network and the deactivation of FAK (Tyr397) might be responsible for the impaired mobility of simulated microgravity-exposed A549 cells. TiO2 NPs exposure inhibited cell migration under two different gravity conditions, but to different degrees, with a milder inhibition under simulated microgravity. Meanwhile, it was found that A549 cells internalized more TiO2 NPs under normal gravity than simulated microgravity, which may account for the lower cytotoxicity and the lighter inhibition of cell migration induced by the same exposure concentration of TiO2 NPs under simulated microgravity at least partially. Our study has provided some tentative information on the effects of TiO2 NPs exposure on cell behaviors under simulated microgravity.

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Topal, Uğur, and Cihan Zamur. "Microgravity, Stem Cells, and Cancer: A New Hope for Cancer Treatment." Stem Cells International 2021 (April 29, 2021): 1–9. http://dx.doi.org/10.1155/2021/5566872.

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Humans are integrated with the environment where they live. Gravitational force plays an important role in shaping the universe, lives, and even cellular biological processes. Research in the last 40 years has shown how exposure to microgravity changes biological processes. Microgravity has been shown to have significant effects on cellular proliferation, invasion, apoptosis, migration, and gene expression, specifically in tumor cells, and these effects may also exist in stem and cancer stem cells. It has also been shown that microgravity changes the effects of chemotherapeutic drugs. Although studies have been carried out in a simulated microgravity environment in cell culture lines, there are few animal experiments or true microgravity studies. Cancer remains one of the most significant problems worldwide. Despite advances in medical science, no definitive strategies have been found for the prevention of cancer formation or to inform treatment. Thus, the microgravity environment is a potential new therapeutic strategy for future cancer treatment. This review will focus on current knowledge on the impact of the microgravity environment on cancer cells, stem cells, and the biological behavior of cancer stem cells.

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Aventaggiato, Michele, Federica Barreca, Enza Vernucci, Mariano Bizzarri, Elisabetta Ferretti, Matteo A. Russo, and Marco Tafani. "Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity." Applied Sciences 10, no. 6 (March 17, 2020): 2028. http://dx.doi.org/10.3390/app10062028.

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Gravity is a constitutive force that influences life on Earth. It is sensed and translated into biochemical stimuli through the so called “mechanosensors”, proteins able to change their molecular conformation in order to amplify external cues causing several intracellular responses. Mechanosensors are widely represented in the human body with important structures such as otholiths in hair cells of vestibular system and statoliths in plants. Moreover, they are also present in the bone, where mechanical cues can cause bone resorption or formation and in muscle in which mechanical stimuli can increase the sensibility for mechanical stretch. In this review, we discuss the role of mechanosensors in two different conditions: normogravity and microgravity, emphasizing their emerging role in microgravity. Microgravity is a singular condition in which many molecular changes occur, strictly connected with the modified gravity force and free fall of bodies. Here, we first summarize the most important mechanosensors involved in normogravity and microgravity. Subsequently, we propose muscle LIM protein (MLP) and sirtuins as new actors in mechanosensing and signaling transduction under microgravity.

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Strube, F., M. Infanger, C. Dietz, A. Romswinkel, and A. Kraus. "Short-term effects of simulated microgravity on morphology and gene expression in human breast cancer cells." Physiology International 106, no. 4 (December 2019): 311–22. http://dx.doi.org/10.1556/2060.106.2019.29.

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Introduction Microgravity has been shown to impose various effects on breast cancer cells. We exposed human breast cancer cells to simulated microgravity and studied morphology and alterations in gene expression. Materials and methods Human breast cancer cells were exposed to simulated microgravity in a random positioning machine (RPM) for 24 h. Morphology was observed under light microscopy, and gene alteration was studied by qPCR. Results After 24 h, formation of three-dimensional structures (spheroids) occurred. BRCA1 expression was significantly increased (1.9×, p < 0.05) in the adherent cells under simulated microgravity compared to the control. Expression of KRAS was significantly decreased (0.6×, p < 0.05) in the adherent cells compared to the control. VCAM1 was significantly upregulated (6.6×, 2.0×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. VIM expression was significantly downregulated (0.45×, 0.44×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. There was no significant alteration in the expression of MAPK1, MMP13, PTEN, and TP53. Conclusions Simulated microgravity induces spheroid formation in human breast cancer cells within 24 h and alters gene expression toward modified adhesion properties, enhanced cell repair, and phenotype preservation. Further insights into the underlying mechanisms could open up the way toward new therapies.

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Thiel, Cora S., Christian Vahlensieck, Timothy Bradley, Svantje Tauber, Martin Lehmann, and Oliver Ullrich. "Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages." International Journal of Molecular Sciences 22, no. 13 (June 23, 2021): 6752. http://dx.doi.org/10.3390/ijms22136752.

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Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.

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Aventaggiato, Michele, Federica Barreca, Laura Vitiello, Simone Vespa, Sergio Valente, Dante Rotili, Antonello Mai, et al. "Role of SIRT3 in Microgravity Response: A New Player in Muscle Tissue Recovery." Cells 12, no. 5 (February 22, 2023): 691. http://dx.doi.org/10.3390/cells12050691.

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Life on Earth has evolved in the presence of a gravity constraint. Any change in the value of such a constraint has important physiological effects. Gravity reduction (microgravity) alters the performance of muscle, bone and, immune systems among others. Therefore, countermeasures to limit such deleterious effects of microgravity are needed considering future Lunar and Martian missions. Our study aims to demonstrate that the activation of mitochondrial Sirtuin 3 (SIRT3) can be exploited to reduce muscle damage and to maintain muscle differentiation following microgravity exposure. To this effect, we used a RCCS machine to simulate microgravity on ground on a muscle and cardiac cell line. During microgravity, cells were treated with a newly synthesized SIRT3 activator, called MC2791 and vitality, differentiation, ROS and, autophagy/mitophagy were measured. Our results indicate that SIRT3 activation reduces microgravity-induced cell death while maintaining the expression of muscle cell differentiation markers. In conclusion, our study demonstrates that SIRT3 activation could represent a targeted molecular strategy to reduce muscle tissue damage caused by microgravity.

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Prieto-Gómez, Isabel, Manuel Ramirez-Sánchez, and Germán Domínguez-Vías. "Physiological effects in a microgravity environment." Revista de Medicina y Cine 17, no. 4 (November 26, 2021): 337–50. http://dx.doi.org/10.14201/rmc2021174337350.

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Nguyen, Nguyen, Gyutae Kim, and Kyu-Sung Kim. "Effects of Microgravity on Human Physiology." Korean Journal of Aerospace and Environmental Medicine 30, no. 1 (April 30, 2020): 25–29. http://dx.doi.org/10.46246/kjasem.30.1.25.

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&NA;. "EFFECTS OF MICROGRAVITY ON CIRCULATORY CONTROL." Medicine & Science in Sports & Exercise 31, Supplement (May 1999): S133. http://dx.doi.org/10.1097/00005768-199905001-00536.

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Watanabe, Satoru. "Effects of Microgravity on Living Organism." Journal of the Society of Mechanical Engineers 97, no. 910 (1994): 791–93. http://dx.doi.org/10.1299/jsmemag.97.910_791.

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WANG, ChongZhen, Yong ZHAO, HaiYing LUO, and MeiFu FENG. "Effects of microgravity on immune cells." Chinese Science Bulletin 58, no. 26 (September 1, 2013): 2679–89. http://dx.doi.org/10.1360/972013-191.

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Guarnieri, Simone, Caterina Morabito, Michele Bevere, Paola Lanuti, and Maria A. Mariggiò. "A Protective Strategy to Counteract the Oxidative Stress Induced by Simulated Microgravity on H9C2 Cardiomyocytes." Oxidative Medicine and Cellular Longevity 2021 (April 20, 2021): 1–18. http://dx.doi.org/10.1155/2021/9951113.

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Microgravity affects human cardiovascular function inducing heart rhythm disturbances and even cardiac atrophy. The mechanisms triggered by microgravity and the search for protection strategies are difficult to be investigated in vivo. This study is aimed at investigating the effects induced by simulated microgravity on a cardiomyocyte-like phenotype. The Random Positioning Machine (RPM), set in a CO2 incubator, was used to simulate microgravity, and H9C2 cell line was used as the cardiomyocyte-like model. H9C2 cells were exposed to simulated microgravity up to 96 h, showing a slower cell proliferation rate and lower metabolic activity in comparison to cell grown at earth gravity. In exposed cells, these effects were accompanied by increased levels of intracellular reactive oxygen species (ROS), cytosolic Ca2+, and mitochondrial superoxide anion. Protein carbonyls, markers of protein oxidation, were significantly increased after the first 48 h of exposition in the RPM. In these conditions, the presence of an antioxidant, the N-acetylcysteine (NAC), counteracted the effects induced by the simulated microgravity. In conclusion, these data suggest that simulated microgravity triggers a concomitant increase of intracellular ROS and Ca2+ levels and affects cell metabolic activity which in turn could be responsible for the slower proliferative rate. Nevertheless, the very low number of detectable dead cells and, more interestingly, the protective effect of NA, demonstrate that simulated microgravity does not have “an irreversible toxic effect” but, affecting the oxidative balance, results in a transient slowdown of proliferation.

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Rai, Balwant, Jasdeep Kaur, and Bernard H. Foing. "Evaluation by an Aeronautic Dentist on the Adverse Effects of a Six-Week Period of Microgravity on the Oral Cavity." International Journal of Dentistry 2011 (2011): 1–5. http://dx.doi.org/10.1155/2011/548068.

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Objective. HDT bed rest condition is a simulated microgravity condition in which subject lies on bed inclined −6 degree feet up. To determine the influence of a simulated microgravity (HDT bed rest) on oral cavity, 10 healthy male volunteers were studied before, during, just after, and after 6 weeks of the simulated microgravity condition of −6° head-down-tilt (HDT) bed rest.Materials and Methods. Facial nerve function, facial sensation, chemosensory system, salivary biomarkers were measured.Results. Lactate dehydrogenase, MIP 1 alpha, malonaldehyde, 8-hydroxydeoxyguanosine, and thiocyanate were found to increase significantly, while flow rate, sodium, potassium, calcium, phosphate, protein, amylase activity, vitamin E and C, and mouth opening were decreased in simulation environments in contradiction to normal. The threshold for monosodium glutamate (MSG) and capsaicin increased during microgravity as compared to normal conditions. Moderate pain of teeth, facial oedema, mild pain, loss of sensation of pain and temperature, decreased tongue, and mandibular movement in simulation microgravity environments were observed.Conclusions. These results suggest that reversible effect of microgravity is oedema of face, change in taste, abnormal expression of face, teeth pain, and xerostomia. Further study will be required on large scale on long-term effects of microgravity on oral cavity to prevent the adverse effects.

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Hekmat, Azadeh, Mojtaba Sadeghi Manesh, Zahra Hajebrahimi, and Shadie Hatamie. "Microgravity-Induced Alterations in the H3.3B (H3F3B) Gene Expression and the Histone H3 Structure." Advanced Science, Engineering and Medicine 12, no. 8 (August 1, 2020): 1084–94. http://dx.doi.org/10.1166/asem.2020.2672.

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It has been believed that microgravity directly can modify the structure, function, and morphology of biosystems and numerous researches have been performed to recognize these alterations. Since histone H3 is an essential protein in the field of epigenetics, this research aimed to evaluate the effects of simulated microgravity on the human H3.3B (H3F3B) gene expression and histone H3 structure. The two-dimensional clinostat was applied for simulating microgravity. Analysis of the gene expression by real-time quantitative PCR revealed that simulated microgravity diminished the expression level of H3.3B considerably (P < 0.001). The UV-Visible absorption and extrinsic fluorescence emission results displayed that after 72 h of simulated microgravity the tertiary structure of histone H3 changed and the surface hydrophobicity of the protein incremented remarkably. Nevertheless, circular dichroism (CD) data showed that simulated microgravity did not perturb the secondary structure of histone H3. Collectively, microgravity can strictly affect the gene expression level of H3.3. Furthermore, histone H3 72 h after subjecting to simulated microgravity can exhibit a molten globule structure. The significance of this research lied in the fact that simulating microgravity can be an effective physical force in gene expression regulation and the protein folding process. This finding could help astrobiologists to realize major health risks for astronaut crews and space travelers and reduce these harmful effects. Furthermore, our observations can open fascinating research lines in astrobiology, biophysics, and exobiology.

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Camberos, Victor, Jonathan Baio, Leonard Bailey, Nahidh Hasaniya, Larry V. Lopez, and Mary Kearns-Jonker. "Effects of Spaceflight and Simulated Microgravity on YAP1 Expression in Cardiovascular Progenitors: Implications for Cell-Based Repair." International Journal of Molecular Sciences 20, no. 11 (June 4, 2019): 2742. http://dx.doi.org/10.3390/ijms20112742.

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Spaceflight alters many processes of the human body including cardiac function and cardiac progenitor cell behavior. The mechanism behind these changes remains largely unknown; however, simulated microgravity devices are making it easier for researchers to study the effects of microgravity. To study the changes that take place in cardiac progenitor cells in microgravity environments, adult cardiac progenitor cells were cultured aboard the International Space Station (ISS) as well as on a clinostat and examined for changes in Hippo signaling, a pathway known to regulate cardiac development. Cells cultured under microgravity conditions, spaceflight-induced or simulated, displayed upregulation of downstream genes involved in the Hippo pathway such as YAP1 and SOD2. YAP1 is known to play a role in cardiac regeneration which led us to investigate YAP1 expression in a sheep model of cardiovascular repair. Additionally, to mimic the effects of microgravity, drug treatment was used to induce Hippo related genes as well as a regulator of the Hippo pathway, miRNA-302a. These studies provide insight into the changes that occur in space and how the effects of these changes relate to cardiac regeneration studies.

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Cortés-Sánchez, José Luis, Jonas Callant, Marcus Krüger, Jayashree Sahana, Armin Kraus, Bjorn Baselet, Manfred Infanger, Sarah Baatout, and Daniela Grimm. "Cancer Studies under Space Conditions: Finding Answers Abroad." Biomedicines 10, no. 1 (December 23, 2021): 25. http://dx.doi.org/10.3390/biomedicines10010025.

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In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential ‘gravisensors’ have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space.

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Kordyum, E. L., and D. K. Chapman. "Plants and microgravity: Patterns of microgravity effects at the cellular and molecular levels." Cytology and Genetics 51, no. 2 (March 2017): 108–16. http://dx.doi.org/10.3103/s0095452717020049.

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Moreno-Villanueva, Maria, Alan Feiveson, Stephanie Krieger, AnneMarie Kay Brinda, Gudrun von Scheven, Alexander Bürkle, Brian Crucian, and Honglu Wu. "Synergistic Effects of Weightlessness, Isoproterenol, and Radiation on DNA Damage Response and Cytokine Production in Immune Cells." International Journal of Molecular Sciences 19, no. 11 (November 21, 2018): 3689. http://dx.doi.org/10.3390/ijms19113689.

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The implementation of rotating-wall vessels (RWVs) for studying the effect of lack of gravity has attracted attention, especially in the fields of stem cells, tissue regeneration, and cancer research. Immune cells incubated in RWVs exhibit several features of immunosuppression including impaired leukocyte proliferation, cytokine responses, and antibody production. Interestingly, stress hormones influence cellular immune pathways affected by microgravity, such as cell proliferation, apoptosis, DNA repair, and T cell activation. These pathways are crucial defense mechanisms that protect the cell from toxins, pathogens, and radiation. Despite the importance of the adrenergic receptor in regulating the immune system, the effect of microgravity on the adrenergic system has been poorly studied. Thus, we elected to investigate the synergistic effects of isoproterenol (a sympathomimetic drug), radiation, and microgravity in nonstimulated immune cells. Peripheral blood mononuclear cells were treated with the sympathomimetic drug isoproterenol, exposed to 0.8 or 2 Gy γ-radiation, and incubated in RWVs. Mixed model regression analyses showed significant synergistic effects on the expression of the β2-adrenergic receptor gene (ADRB2). Radiation alone increased ADRB2 expression, and cells incubated in microgravity had more DNA strand breaks than cells incubated in normal gravity. We observed radiation-induced cytokine production only in microgravity. Prior treatment with isoproterenol clearly prevents most of the microgravity-mediated effects. RWVs may be a useful tool to provide insight into novel regulatory pathways, providing benefit not only to astronauts but also to patients suffering from immune disorders or undergoing radiotherapy.

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Ma, Jin, Chadi I. Kahwaji, Zhenmin Ni, Nosratola D. Vaziri, and Ralph E. Purdy. "Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content." Journal of Applied Physiology 94, no. 1 (January 1, 2003): 83–92. http://dx.doi.org/10.1152/japplphysiol.00294.2002.

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The aim of the present work was to investigate the alterations in nitric oxide synthase (NOS) expression and nitrate and nitrite (NOx) content of different arteries from simulated microgravity rats. Male Wistar rats were randomly assigned to either a control group or simulated microgravity group. For simulating microgravity, animals were subjected to hindlimb unweighting (HU) for 20 days. Different arterial tissues were removed for determination of NOS expression and NOx. Western blotting was used to measure endothelial NOS (eNOS) and inducible NOS (iNOS) protein content. Total concentrations of NOx, stable metabolites of nitric oxide, were determined by the chemiluminescence method. Compared with controls, isolated vessels from simulated microgravity rats showed a significant increase in both eNOS and iNOS expression in carotid arteries and thoracic aorta and a significant decrease in eNOS and iNOS expression of mesenteric arteries. The eNOS and iNOS content of cerebral arteries, as well as that of femoral arteries, showed no differences between the two groups. Concerning NOx, vessels from HU rats showed an increase in cerebral arteries, a decrease in mesenteric arteries, and no change in carotid artery, femoral artery and thoracic aorta. These data indicated that there were differential alterations in NOS expression and NOx of different arteries after hindlimb unweighting. We suggest that these changes might represent both localized adaptations to differential body fluid redistribution and other factors independent of hemodynamic shifts during simulated microgravity.

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Sayenko, D. G., and E. S. Tomilovskaya. "EFFECTS OF MICROGRAVITY ON POSTURAL CONTROL: CONCEPTS PIONEERED BY I.B. KOZLOVSKAYA." Aerospace and Environmental Medicine 54, no. 6 (2020): 43–49. http://dx.doi.org/10.21687/0233-528x-2020-54-6-43-49.

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Professor Inesa B. Kozlovskaya led a series of multifaceted systematic studies that explored the impact of space flights and ground-based models of microgravity on motor control in humans. Based on data from these studies, she postulated that the cascade of microgravity-induced impairments in postural control is largely associated with deactivation of the muscle tone system. The decrease in tone of antigravity muscles, in turn, is triggered by the deficit and distortion of gravity-specific sensory input from tactile mechanoreceptors and otoliths. Further studies led by Prof. Kozlovskaya demonstrated that the quality of postural control following space flights depends on the type and amount of in-flight physical activity. These fundamental works have elucidated mechanisms through which microgravity impacts motor control and are instrumental in developing advanced countermeasure means of the negative sensorimotor effects caused by space flights.

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Degan, Paolo, Katia Cortese, Alessandra Pulliero, Silvia Bruno, Maria Cristina Gagliani, Matteo Congiu, and Alberto Izzotti. "Simulated Microgravity Effects on Human Adenocarcinoma Alveolar Epithelial Cells: Characterization of Morphological, Functional, and Epigenetic Parameters." International Journal of Molecular Sciences 22, no. 13 (June 28, 2021): 6951. http://dx.doi.org/10.3390/ijms22136951.

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Background: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. Methods: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. Results: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. Conclusions: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance.

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Yuan, Mengqin, Haizhou Liu, Shunheng Zhou, Xu Zhou, Yu-e. Huang, Fei Hou, and Wei Jiang. "Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis." International Journal of Molecular Sciences 21, no. 20 (October 14, 2020): 7585. http://dx.doi.org/10.3390/ijms21207585.

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Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles in human peripheral blood lymphocytes cultured in modeled microgravity. Two hundred and thirty dysregulated TF-miRNA (transcription factor and microRNA) feed-forward loops (FFLs) were identified in microgravity. The immune, cardiovascular, endocrine, nervous and skeletal system subnetworks were constructed according to the functions of dysregulated FFLs. Taking the skeletal system as an example, most of genes and miRNAs in the subnetwork were involved in bone loss. In addition, several drugs have been predicted to have potential to reduce bone loss, such as traditional Chinese medicines Emodin and Ginsenoside Rh2. Furthermore, we investigated the relationships between microgravity and 20 cancer types, and found that most of cancers might be promoted by microgravity. For example, rectum adenocarcinoma (READ) might be induced by microgravity through reducing antigen presentation and suppressing IgA-antibody-secreting cells’ migration. Collectively, TF-miRNA FFL might provide a novel mechanism to elucidate the changes induced by microgravity, serve as drug targets to relieve microgravity effects, and give new insights to explore the relationships between microgravity and cancers.

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Lau, Cheryl, Alexander Mukasyan, Aleksey Pelekh, and Arvind Varma. "Mechanistic studies in combustion synthesis of NiAl–TiB2 composites: Effects of gravity." Journal of Materials Research 16, no. 6 (June 2001): 1614–25. http://dx.doi.org/10.1557/jmr.2001.0224.

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Combustion synthesis (CS) of NiAl-based materials reinforced by TiB2 particles was investigated under both terrestrial and microgravity conditions. The synthesized metal matrix composites (MMC) are characterized by very fine (<1 μm) reinforced particulates, which have strong bonding along their entire surface with matrix (NiAl) and are distributed uniformly in it. It was found that microgravity leads to a decrease in the average TiB2 particle size, while higher volume fraction of NiAl component in the material leads to the formation of coarser reinforced particulates. The mechanism of structure formation of different MMCs during CS was identified by using the quenching technique. For example, it was shown that TiB2 grains appear due to crystallization from the complex (Ni–Al–Ti–B) liquid solution formed in the combustion front. An overall decrease of microstructural transformation rates was observed under microgravity.

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Berisio, R., L. Vitagliano, G. Sorrentino, L. Carotenuto, C. Piccolo, L. Mazzarella, and A. Zagari. "Effects of microgravity on the crystal quality of a collagen-like polypeptide." Acta Crystallographica Section D Biological Crystallography 56, no. 1 (January 1, 2000): 55–61. http://dx.doi.org/10.1107/s0907444999014158.

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(Pro-Pro-Gly)10 is one of the most widely studied collagen polypeptide models. Microgravity crystal growth of (Pro-Pro-Gly)10 was carried out in the Advanced Protein Crystallization Facility aboard the Space Shuttle Discovery during the STS-95 mission. Crystals were successfully grown in all experiments, using both dialysis and free-interface diffusion methods. The quality of the microgravity-grown crystals and of ground-grown counterparts was assessed by X-ray synchrotron diffraction. Microgravity-grown crystals exhibited a significant improvement in terms of dimensions and resolution limit. As previously reported, crystals were orthorhombic, space group P212121. However, the diffraction pattern showed weak reflections, never previously measured, that were consistent with new unit-cell parameters a = 26.9, b = 26.4, c = 182.5 Å. This allowed the derivation of a new model for the arrangement of the triple-helical molecules in the crystals.

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Sokolovskaya, Alisa, Ekaterina Korneeva, Danila Zaichenko, Edward Virus, Dmitry Kolesov, Aleksey Moskovtsev, and Aslan Kubatiev. "Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4 Cells Exposed to a Random Positioning Machine." International Journal of Molecular Sciences 21, no. 3 (January 28, 2020): 855. http://dx.doi.org/10.3390/ijms21030855.

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Experiments from flight- and ground-based model systems suggest that unexpected alterations of the human lymphoblastoid cell line Jurkat, as well as effects on cell growth, metabolism, and apoptosis, can occur in altered gravity conditions. Using a desktop random positioning machine (RPM), we investigated the effects of simulated microgravity on Jurkat cells and their multidrug-resistant subline, Jurkat/A4 cells. The viability of Jurkat/A4 cells decreased after simulated microgravity in contrast with the Jurkat cells. At the same time, the viability between the experimental Jurkat cells and control Jurkat cells was not significantly different. Of note, Jurkat cells appeared as less susceptible to apoptosis than their multidrug-resistant clone Jurkat/A4 cells, whereas cell-cycle analysis showed that the percentage of Jurkat/A4 cells in the S-phase was increased after 72 and 96 h of RPM-simulated microgravity relative to their static counterparts. The differences in Jurkat cells at all phases between static and simulated microgravity were not significant. The surface expression of the intercellular adhesion molecule 3 (ICAM-3)—also known as cluster of differentiation (CD)50—protein was changed for Jurkat/A4 cells following exposure to the RPM. Changes in cell morphology were observed in the Jurkat/A4 cells after 96 h of RPM-simulated microgravity. Thus, we concluded that Jurkat/A4 cells are more sensitive to RPM-simulated microgravity as compared with the parental Jurkat cell line. We also suggest that intercellular adhesion molecule 3 may be an important adhesion molecule involved in the induction of leukocyte apoptosis. The Jurkat/A4 cells with an acquired multidrug resistance phenotype could be a useful model for studying the effects of simulated microgravity and testing anticancer drugs.

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Calcagno, Gaetano, Jeremy Jeandel, Jean-Pol Frippiat та Sandra Kaminski. "Simulated Microgravity Disrupts Nuclear Factor κB Signaling and Impairs Murine Dendritic Cell Phenotype and Function". International Journal of Molecular Sciences 24, № 2 (15 січня 2023): 1720. http://dx.doi.org/10.3390/ijms24021720.

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During spaceflights, astronauts face different forms of stress (e.g., socio-environmental and gravity stresses) that impact physiological functions and particularly the immune system. In this context, little is known about the effect of such stress on dendritic cells (DCs). First, we showed that hypergravity, but not chronic ultra-mild stress, a socio-environmental stress, induced a less mature phenotype characterized by a decreased expression of MHCII and co-stimulatory molecules. Next, using the random positioning machine (RPM), we studied the direct effects of simulated microgravity on either splenic DCs or Flt-3L-differentiated bone marrow dendritic cells (BMDCs). Simulated microgravity was found to reduce the BM-conventional DC (cDC) and splenic cDC activation/maturation phenotype. Consistent with this, BMDCs displayed a decreased production of pro-inflammatory cytokines when exposed to microgravity compared to the normogravity condition. The induction of a more immature phenotype in microgravity than in control DCs correlated with an alteration of the NFκB signaling pathway. Since the DC phenotype is closely linked to their function, we studied the effects of microgravity on DCs and found that microgravity impaired their ability to induce naïve CD4 T cell survival, proliferation, and polarization. Thus, a deregulation of DC function is likely to induce immune deregulation, which could explain the reduced efficiency of astronauts’ immune response.

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Short, H. David. "Cardiovascular Effects of Microgravity: Evolution of Understanding." Otolaryngology–Head and Neck Surgery 118, no. 3_suppl (March 1998): s52—s54. http://dx.doi.org/10.1016/s0194-59989870010-5.

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The understanding of cardiovascular effects of spaceflight has evolved throughout the course of the American manned spaceflight program. Originally descriptive in nature, the present understanding is based on empiric measurements of vascular volume, cardiac output, vascular reflexes, and peripheral and central autonomic control. More detailed understanding of cardiovascular effects has allowed us to separate those symptoms from symptoms caused by musculoskeletal or neurovestibular abnormalities. (Otolaryngol Head Neck Surg 1998;118:S52-S54.)

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38

Kordyum, Elizabeth L. "Effects of microgravity and clinostating on plants." Giornale botanico italiano 127, no. 3 (January 1993): 377–85. http://dx.doi.org/10.1080/11263509309431019.

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39

SHORT, H. "Cardiovascular effects of microgravity: Evolution of understanding." Otolaryngology - Head and Neck Surgery 118, no. 3 (March 1998): S52—S54. http://dx.doi.org/10.1016/s0194-5998(98)70010-5.

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Marco, R., I. Vernós, J. González-Jurado, M. Maroto, and M. Carratalá. "Microgravity effects on insect development and aging." Cell Differentiation and Development 27 (August 1989): 182. http://dx.doi.org/10.1016/0922-3371(89)90551-0.

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Rose, Michael I., Dale C. Brown, Neil R. Pellis, Christopher A. Crisera, Kari L. Colen, Michael T. Longaker, and George K. Gittes. "Effects of microgravity on the embryonic pancreas." In Vitro Cellular & Developmental Biology - Animal 35, no. 10 (November 1999): 560–63. http://dx.doi.org/10.1007/s11626-999-0092-7.

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Boada, M., A. Perez-Poch, M. Ballester, S. García-Monclús, D. V. González, S. García, P. N. Barri, and A. Veiga. "Microgravity effects on frozen human sperm samples." Journal of Assisted Reproduction and Genetics 37, no. 9 (July 18, 2020): 2249–57. http://dx.doi.org/10.1007/s10815-020-01877-5.

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Arfat, Yasir, Wei-Zhong Xiao, Salman Iftikhar, Fan Zhao, Di-Jie Li, Yu-Long Sun, Ge Zhang, Peng Shang, and Ai-Rong Qian. "Physiological Effects of Microgravity on Bone Cells." Calcified Tissue International 94, no. 6 (April 1, 2014): 569–79. http://dx.doi.org/10.1007/s00223-014-9851-x.

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44

Urban, David L., Paul Ferkul, Sandra Olson, Gary A. Ruff, John Easton, James S. T'ien, Ya-Ting T. Liao, et al. "Flame spread: Effects of microgravity and scale." Combustion and Flame 199 (January 2019): 168–82. http://dx.doi.org/10.1016/j.combustflame.2018.10.012.

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45

Miller, Joseph D., Brain A. McMillen, Mona M. McConnaughey, Helen L. Williams, and Charles A. Fuller. "Effects of microgravity on brain neurotransmitter receptors." European Journal of Pharmacology 161, no. 2-3 (February 1989): 165–71. http://dx.doi.org/10.1016/0014-2999(89)90839-x.

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Layne, Charles S., and Brian S. Spooner. "Microgravity effects on “postural” muscle activity patterns." Advances in Space Research 14, no. 8 (August 1994): 381–84. http://dx.doi.org/10.1016/0273-1177(94)90427-8.

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Hughes-Fulford, M., and M. L. Lewis. "Effects of Microgravity on Osteoblast Growth Activation." Experimental Cell Research 224, no. 1 (April 1996): 103–9. http://dx.doi.org/10.1006/excr.1996.0116.

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Belyavskaya, N. A. "Free and membrane-bound calcium in microgravity and microgravity effects at the membrane level." Advances in Space Research 17, no. 6-7 (January 1996): 169–77. http://dx.doi.org/10.1016/0273-1177(95)00631-n.

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Liang, Liwen, Huili Li, Ting Cao, Lina Qu, Lulu Zhang, Guo-Chang Fan, Peter A. Greer, Jianmin Li, Douglas L. Jones, and Tianqing Peng. "Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways." Journal of Biological Chemistry 295, no. 49 (September 28, 2020): 16840–51. http://dx.doi.org/10.1074/jbc.ra119.011890.

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The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

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Yim, Jaewoo, Sung Won Cho, Beomhee Kim, Sungwoo Park, Yong Hee Han, and Sang Woo Seo. "Transcriptional Profiling of the Probiotic Escherichia coli Nissle 1917 Strain under Simulated Microgravity." International Journal of Molecular Sciences 21, no. 8 (April 11, 2020): 2666. http://dx.doi.org/10.3390/ijms21082666.

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Long-term space missions affect the gut microbiome of astronauts, especially the viability of some pathogens. Probiotics may be an effective solution for the management of gut microbiomes, but there is a lack of studies regarding the physiology of probiotics in microgravity. Here, we investigated the effects of microgravity on the probiotic Escherichia coli Nissle 1917 (EcN) by comparing transcriptomic data during exponential and stationary growth phases under simulated microgravity and normal gravity. Microgravity conditions affected several physiological features of EcN, including its growth profile, biofilm formation, stress responses, metal ion transport/utilization, and response to carbon starvation. We found that some changes, such as decreased adhesion ability and acid resistance, may be disadvantageous to EcN relative to gut pathogens under microgravity, indicating the need to develop probiotics optimized for space flight.

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