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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 31089

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Dr. Daniela Grimm

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Guest Editor

1. Institute of Biomedicine, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark
2. Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University Magdeburg, Pfälzerplatz 2, 39106 Magdeburg, Germany
Interests: breast cancer; thyroid cancer; prostate cancer; cell biology; gravitational biology; space medicine; tissue engineering; pharmacology; apoptosis; SOX transcription factors
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Special Issue Information

Dear Colleagues,

This is the second volume of the Special Issue "Microgravity and Space Medicine". In the near future, humans will return to the Moon and start expeditions to Mars and to other planets. In addition, there will be an increase in space tourism, which will lead to a high number of manned spaceflights. A long-term stay in space can influence the health of space travelers and can result in various health problems.

This Special Issue focuses on the impact of altered gravity conditions on mammalian cells, animals, and humans during spaceflights. It addresses the impact of cosmic radiation, available countermeasures, and possible applications on Earth.

The Special Issue will also publish studies investigating the impact of real and simulated microgravity on human and animal cells as well as on microorganisms. A special focus lies on projects in the field of cancer research and tissue engineering. Ground-based facilities available to simulate microgravity on Earth can be used for studying changes in various cell types.

Articles and reviews will be published that examine either the molecular biological background of external signals in cancer and other diseases or the cellular mechanisms responsible for the manifold changes occurring in cells and animals when exposed to microgravity. In addition, manuscripts reporting on experiments utilizing microgravity for tissue engineering purposes and on the bioprinting of tissues used in microgravity applications will be accepted for publication.

Dr. Daniela Grimm
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

space flight
rocket flight
parabolic flight mission
cancer research
animals
cells
humans
tissue engineering
immune system
microgravity-related health problems
cosmic radiation

Related Special Issue

Microgravity and Space Medicine in International Journal of Molecular Sciences (17 articles)

Published Papers (10 papers)

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Editorial

Jump to: Research

6 pages, 218 KiB

Open AccessEditorial

Microgravity and Space Medicine 2.0

by Daniela Grimm

Int. J. Mol. Sci. 2022, 23(8), 4456; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084456 - 18 Apr 2022

Viewed by 2388

Abstract

This Special Issue (SI), “Microgravity and Space Medicine 2 [...] Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

Research

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11 pages, 1395 KiB

Open AccessArticle

Molecular Cross-Talk between Gravity- and Light-Sensing Mechanisms in Euglena gracilis

by Adeel Nasir, Peter Rolf Richter, Aude Le Bail, Viktor Daiker, Julia Stoltze, Binod Prasad, Sebastian Michael Strauch and Michael Lebert

Int. J. Mol. Sci. 2022, 23(5), 2776; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052776 - 03 Mar 2022

Cited by 2 | Viewed by 1997

Abstract

Euglena gracilis is a photosynthetic flagellate. To acquire a suitable position in its surrounding aquatic environment, it exploits light and gravity primarily as environmental cues. Several physiological studies have indicated a fine-tuned relationship between gravity sensing (gravitaxis) and light sensing in E. gracilis. However, the underlying molecular mechanism is largely unknown. The photoreceptor photoactivated adenylyl cyclase (PAC) has been studied for over a decade. Nevertheless, no direct/indirect interaction partner (upstream/downstream) has been reported for PAC. It has been shown that a specific protein, kinase A (PKA), showed to be involved in phototaxis and gravitaxis. The current study reports the localization of the specific PKA and its relationship with PAC. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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20 pages, 4867 KiB

Open AccessArticle

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

by Valeria Fedeli, Alessandra Cucina, Simona Dinicola, Gianmarco Fabrizi, Angela Catizone, Luisa Gesualdi, Simona Ceccarelli, Abdel Halim Harrath, Saleh H. Alwasel, Giulia Ricci, Paola Pedata, Mariano Bizzarri and Noemi Monti

Int. J. Mol. Sci. 2022, 23(4), 2163; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042163 - 16 Feb 2022

Cited by 8 | Viewed by 2143

Abstract

Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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19 pages, 4276 KiB

Open AccessArticle

Combined Impact of Magnetic Force and Spaceflight Conditions on Escherichia coli Physiology

by Pavel A. Domnin, Vladislav A. Parfenov, Alexey S. Kononikhin, Stanislav V. Petrov, Nataliya V. Shevlyagina, Anastasia Yu. Arkhipova, Elizaveta V. Koudan, Elizaveta K. Nezhurina, Alexander G. Brzhozovskiy, Anna E. Bugrova, Anastasia M. Moysenovich, Alexandr A. Levin, Pavel A. Karalkin, Frederico D. A. S. Pereira, Vladimir G. Zhukhovitsky, Elena S. Lobakova, Vladimir A. Mironov, Evgeny N. Nikolaev, Yusef D. Khesuani and Svetlana A. Ermolaeva

Int. J. Mol. Sci. 2022, 23(3), 1837; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031837 - 06 Feb 2022

Cited by 8 | Viewed by 2265

Abstract

Changes in bacterial physiology caused by the combined action of the magnetic force and microgravity were studied in Escherichia coli grown using a specially developed device aboard the International Space Station. The morphology and metabolism of E. coli grown under spaceflight (SF) or combined spaceflight and magnetic force (SF + MF) conditions were compared with ground cultivated bacteria grown under standard (control) or magnetic force (MF) conditions. SF, SF + MF, and MF conditions provided the up-regulation of Ag43 auto-transporter and cell auto-aggregation. The magnetic force caused visible clustering of non-sedimenting bacteria that formed matrix-containing aggregates under SF + MF and MF conditions. Cell auto-aggregation was accompanied by up-regulation of glyoxylate shunt enzymes and Vitamin B12 transporter BtuB. Under SF and SF + MF but not MF conditions nutrition and oxygen limitations were manifested by the down-regulation of glycolysis and TCA enzymes and the up-regulation of methylglyoxal bypass. Bacteria grown under combined SF + MF conditions demonstrated superior up-regulation of enzymes of the methylglyoxal bypass and down-regulation of glycolysis and TCA enzymes compared to SF conditions, suggesting that the magnetic force strengthened the effects of microgravity on the bacterial metabolism. This strengthening appeared to be due to magnetic force-dependent bacterial clustering within a small volume that reinforced the effects of the microgravity-driven absence of convectional flows. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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17 pages, 2422 KiB

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

by Justin Braveboy-Wagner, Yoav Sharoni and Peter I. Lelkes

Int. J. Mol. Sci. 2022, 23(1), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010136 - 23 Dec 2021

Cited by 6 | Viewed by 2326

Abstract

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

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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24 pages, 24249 KiB

Open AccessArticle

Changes in Exosomal miRNA Composition in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

by Petra M. Wise, Paolo Neviani, Stefan Riwaldt, Thomas J. Corydon, Markus Wehland, Markus Braun, Marcus Krüger, Manfred Infanger and Daniela Grimm

Int. J. Mol. Sci. 2021, 22(23), 12841; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312841 - 27 Nov 2021

Cited by 10 | Viewed by 2545

Abstract

As much as space travel and exploration have been a goal since humankind looked up to the stars, the challenges coming with it are manifold and difficult to overcome. Therefore, researching the changes the human organism undergoes following exposure to weightlessness, on a cellular or a physiological level, is imperative to reach the goal of exploring space and new planets. Building on the results of our CellBox-1 experiment, where thyroid cancer cells were flown to the International Space Station, we are now taking advantage of the newest technological opportunities to gain more insight into the changes in cell–cell communication of these cells. Analyzing the exosomal microRNA composition after several days of microgravity might elucidate some of the proteomic changes we have reported earlier. An array scan of a total of 754 miRNA targets revealed more than 100 differentially expressed miRNAs in our samples, many of which have been implicated in thyroid disease in other studies. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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14 pages, 2115 KiB

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Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

by Jiranuwat Sapudom, Mei ElGindi, Marc Arnoux, Nizar Drou, Anna Garcia-Sabaté and Jeremy C. M. Teo

Int. J. Mol. Sci. 2021, 22(21), 11911; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111911 - 02 Nov 2021

Cited by 16 | Viewed by 7458

Abstract

Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling. In this work, we utilized collagen-based three-dimensional (3D) matrices to mimic interstitial tissue and studied fibroblast differentiation under simulated microgravity (sµG). Our results demonstrated that alpha-smooth muscle actin (αSMA) expression and translocation of Smad2/3 into the cell nucleus were reduced upon exposure to sµG compared to the 1g control, which suggests the impairment of fibroblast differentiation under sµG. Moreover, matrix remodeling and production were decreased under sµG, which is in line with the impaired fibroblast differentiation. We further investigated changes on a transcriptomic level using RNA sequencing. The results demonstrated that sµG has less effect on fibroblast transcriptomes, while sµG triggers changes in the transcriptome of myofibroblasts. Several genes and biological pathways found through transcriptome analysis have previously been reported to impair fibroblast differentiation. Overall, our data indicated that fibroblast differentiation, as well as matrix production and remodeling, are impaired in 3D culture under sµG conditions. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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19 pages, 15320 KiB

Open AccessArticle

Agrobacterium tumefaciens-Mediated Nuclear Transformation of a Biotechnologically Important Microalga—Euglena gracilis

by Ina Becker, Binod Prasad, Maria Ntefidou, Viktor Daiker, Peter Richter and Michael Lebert

Int. J. Mol. Sci. 2021, 22(12), 6299; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126299 - 11 Jun 2021

Cited by 12 | Viewed by 4102

Abstract

Euglena gracilis (E. gracilis) is an attractive organism due to its evolutionary history and substantial potential to produce biochemicals of commercial importance. This study describes the establishment of an optimized protocol for the genetic transformation of E. gracilis mediated by Agrobacterium (A. tumefaciens). E. gracilis was found to be highly sensitive to hygromycin and zeocin, thus offering a set of resistance marker genes for the selection of transformants. A. tumefaciens-mediated transformation (ATMT) yielded hygromycin-resistant cells. However, hygromycin-resistant cells hosting the gus gene (encoding β-glucuronidase (GUS)) were found to be GUS-negative, indicating that the gus gene had explicitly been silenced. To circumvent transgene silencing, GUS was expressed from the nuclear genome as transcriptional fusions with the hygromycin resistance gene (hptII) (encoding hygromycin phosphotransferase II) with the foot and mouth disease virus (FMDV)-derived 2A self-cleaving sequence placed between the coding sequences. ATMT of Euglena with the hptII-2A–gus gene yielded hygromycin-resistant, GUS-positive cells. The transformation was verified by PCR amplification of the T-DNA region genes, determination of GUS activity, and indirect immunofluorescence assays. Cocultivation factors optimization revealed that a higher number of transformants was obtained when A. tumefaciens LBA4404 (A₆₀₀ = 1.0) and E. gracilis (A₇₅₀ = 2.0) cultures were cocultured for 48 h at 19 °C in an organic medium (pH 6.5) containing 50 µM acetosyringone. Transformation efficiency of 8.26 ± 4.9% was achieved under the optimized cocultivation parameters. The molecular toolkits and method presented here can be used to bioengineer E. gracilis for producing high-value products and fundamental studies. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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17 pages, 12680 KiB

Open AccessArticle

Simulated Microgravity Remodels Extracellular Matrix of Osteocommitted Mesenchymal Stromal Cells

by Ivan Zhivodernikov, Andrey Ratushnyy and Ludmila Buravkova

Int. J. Mol. Sci. 2021, 22(11), 5428; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115428 - 21 May 2021

Cited by 7 | Viewed by 2153

Abstract

The extracellular matrix (ECM) is the principal structure of bone tissue. Long-term spaceflights lead to osteopenia, which may be a result of the changes in composition as well as remodeling of the ECM by osteogenic cells. To elucidate the cellular effects of microgravity, human mesenchymal stromal cells (MSCs) and their osteocommitted progeny were exposed to simulated microgravity (SMG) for 10 days using random positioning machine (RPM). After RPM exposure, an imbalance of MSC collagen/non-collagen ratio at the expense of a decreased level of collagenous proteins was detected. At the same time, the secretion of proteases (cathepsin A, cathepsin D, MMP3) was increased. No significant effects of SMG on the expression of stromal markers and cell adhesion molecules on the MSC surface were noted. Upregulation of COL11A1, CTNND1, TIMP3, and TNC and downregulation of HAS1, ITGA3, ITGB1, LAMA3, MMP1, and MMP11 were detected in RPM exposed MSCs. ECM-associated transcriptomic changes were more pronounced in osteocommitted progeny. Thus, 10 days of SMG provokes a decrease in the collagenous components of ECM, probably due to the decrease in collagen synthesis and activation of proteases. The presented data demonstrate that ECM-associated molecules of both native and osteocommitted MSCs may be involved in bone matrix reorganization during spaceflight. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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15 pages, 2434 KiB

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Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression

by Hong-Min Wu, Sang-Gil Lee, Choong-Sik Oh and Sang-Geon Kim

Int. J. Mol. Sci. 2021, 22(9), 4901; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094901 - 05 May 2021

Cited by 3 | Viewed by 2028

Abstract

Hypergravity conditions may subject the kidney to intrinsic stress and lead to hemodynamic kidney dysfunction. However, the mechanisms underlying this phenomenon remain unclear. Accumulation of unfolded proteins in the endoplasmic reticulum (i.e., ER stress) is often observed in kidney diseases. Therefore, this study investigated whether hypergravity stress alters acetaminophen-induced renal toxicity in vivo, as well as the molecular mechanisms involved in this process. C57BL/6 mice were submitted to one or three loads of +9 Gx hypergravity for 1 h with or without acetaminophen (APAP) treatment. The protein levels of cell survival markers, including pAKT and pCREB, were decreased in the kidney after acetaminophen treatment with a single hypergravity load. Additionally, the combined treatment increased kidney injury markers, serum creatinine, and Bax, Bcl2, and Kim-1 transcript levels and enhanced ER stress-related markers were further. Moreover, multiple hypergravity loads enabled mice to overcome kidney injury, as indicated by decreases in serum creatinine content and ER stress marker levels, along with increased cell viability indices. Similarly, multiple hypergravity loads plus APAP elevated miR-122 levels in the kidney, which likely originated from the liver, as the levels of primary miR-122 increased only in the liver and not the kidney. Importantly, this phenomenon may contribute to overcoming hypergravity-induced kidney injury. Taken together, our results demonstrate that APAP-exposed mice submitted to a single load of hypergravity exhibited more pronounced kidney dysfunction due to increased ER stress, which may be overcome by repetitive hypergravity loads presumably due to increased production of miR-122 in the liver. Thus, our study provides novel insights into the mechanisms by which hypergravity stress plus APAP medication induce kidney injury, which may be overcome by repeated hypergravity exposure. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine 2.0)

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