: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term ...spaceflight, which results in decreased bone formation.
: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro.
: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (
), collagen type 1 alpha-1(
)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity.
: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.
As considerations are being made for the limitations and safety of long-term human spaceflight, the vasculature is important given its connection to and impact on numerous organ systems. As a major ...constituent of blood vessels, vascular smooth muscle cells are of interest due to their influence over vascular tone and function. Additionally, vascular smooth muscle cells are responsive to pressure and flow changes. Therefore, alterations in these parameters under conditions of microgravity can be functionally disruptive. As such, here we review and discuss the existing literature that assesses the effects of microgravity, both actual and simulated, on smooth muscle cells. This includes the various methods for achieving or simulating microgravity, the animal models or cells used, and the various durations of microgravity assessed. We also discuss the various reported findings in the field, which include changes to cell proliferation, gene expression and phenotypic shifts, and renin-angiotensin-aldosterone system (RAAS), nitric oxide synthase (NOS), and Ca
signaling. Additionally, we briefly summarize the literature on smooth muscle tissue engineering in microgravity as well as considerations of radiation as another key component of spaceflight to contextualize spaceflight experiments, which by their nature include radiation exposure. Finally, we provide general recommendations based on the existing literature's focus and limitations.
•Microfluidics can be used for up-scaled processing of covalent-organic frameworks.•Microfluidics offers an exquisite control over mixing regimes.•Mixing regimes can tailor the shape, morphology and ...surface integration of COFs.•Microfluidics can reveal morphogenesis of COFs via simulated microgravity.
Nearly twenty years since the discovery of covalent-organic frameworks (COFs), most of the research on these materials has been focused on the rational design of new structures. Recently, the quest for discovering the functionalities and potential applications of these crystalline materials has attracted the attention of many researchers. While the number of reports regarding these two aspects within the COF research area is continuously growing, in order to achieve their full potential, the processability aspect of COFs also needs to be addressed. In this review article, we examine the opportunities that flow-based technologies offer regarding (a) the continuous synthesis of COFs, and (b) the processing of these materials into functional surfaces and devices (e.g. thin films and 3D structures), both aspects being ultimately amenable to industrial scale up.
Acid resistance is critical for the survival of Escherichia coli O157:H7 in acidic environments. The representative space environment microgravity is known to have a great impact on bacteria, but the ...acid stress response of E. coli O157:H7 under microgravity conditions remains unclear. Here, we show that the acid resistance of sbacteria is altered by the upregulation of related resistance systems. All tested E. coli O157:H7 strains (ATCC 35150, 43889, 43890, and 43895) survived better in acidified Luria-Bertani medium (pH 3.5) under low-shear modeled microgravity (LSMMG) than under normal gravity (NG, counterpart condition). For example, after 72 h of cultivation under acidic conditions, bacterial populations in the LSMMG cultures reached 5.2–6.7 log CFU/ml, while those in the NG cultures reached 2.4–5.6 log CFU/ml. Our transcriptomic analysis studies on E. coli O157:H7 under LSMMG conditions also provided supportive data of the increase in the acid stress response, with a 2.18 to 3.44 log2 fold change in the acid resistance system 1 (rpoS) and 2 (gad) and chaperone related genes (hdeA and hdeB). Comparing D-values before and after acid shock at pH 3.5, the increase in thermal cross-protection power was more remarkable in the LSMMG cultures than in the NG cultures. In the case of E. coli O157:H7 ATCC 35150, the D-values in the LSMMG and NG cultures at 55 °C after acid shock increased by 17.1 and 10.8 min, respectively, compared to the control. Our findings illustrated that simulated microgravity impacts the acid resistance of E. coli O157:H7 as well as the acquisition of thermal cross-protection power, suggesting that alterations in bacterial responses to the space environment could be a health threat.
Spaceflight and microgravity has a significant impact on the immune, central nervous, bone, and muscle support and cardiovascular systems. However, limited studies are available on the adverse ...effects of long-term microgravity on the intestinal microbiota, metabolism, and its relationships. In this study, a ground-based simulated microgravity (SMG) mouse model was established to evaluate the impact of long-term microgravity on gut microbiota and metabolome. After 8 weeks of SMG, alterations of the intestinal microbiota and metabolites were detected using 16S rRNA sequencing and untargeted metabolomics. Compared to the control, no significant differences in α-diversity were observed at weeks 2, 4 and 8. Nevertheless, there were clear differences in community structures at different time points. The phylum
significantly declined from 2 to 8 weeks of SMG, yet the relative abundance of
and
expanded remarkably at weeks 8. SMG decreased the genus of
and increased
significantly throughout the period of 8 weeks. Besides, Genus
,
,
,
,
,
,
,
and
were identified as biomarkers for SMG group.
, and
dropped at week 2, which tend to recover at week 4, except for
.
and
declined significantly, while
and
elevated at week 8. Furthermore, intestinal metabolome analysis showed that 129 were upregulated and 146 metabolites were downregulated in SMG. Long-term SMG most affected steroid hormone biosynthesis, tryptophan, cysteine, methionine, arginine, proline metabolism, and histidine metabolism. Correlated analysis suggested that the potential beneficial taxa
, and
were negatively associated with tryptophan, histidine, arginine, and proline metabolism, but positively with steroid hormone biosynthesis. Yet
and
were positively correlated with arginine, proline, tryptophan, and histidine metabolism, while negatively associated with steroid hormone biosynthesis. These results suggest that Long-term SMG altered the community of intestinal microbiota, and then further disturbed intestinal metabolites and metabolic pathways, which have great potential to help understand and provide clues for revealing the mechanisms of long-term SMG involved diseases.
Bone loss occurs in astronauts during long-term space flight, and hardly recover to the normal level after back to the earth. This is because the mechanism of microgravity-induced osteoporosis is ...still unclear. Advanced glycation end products (AGEs) are formed between reducing sugars and long-lived proteins and are verified to be the pathogenic mechanism for diabetic and aging osteoporosis. These non-enzymatic glycation products are considered to have adverse effects on bone metabolism and bone quality which consist of bone microstructure and bone organic matrix. However, whether AGEs accumulation happened under microgravity is not clear yet. AGEs accumulation can be induced by hyperglycemia in diabetic patients and senior people. Hyperglycemia was also found to occur in astronauts during spaceflight or under simulated microgravity, however, whether it also can cause bone matrix AGEs accumulation remains unrevealed, and whether AGEs involve in the disuse osteoporosis is as well not clear yet. Therefore, in this study, we explored the AGEs changes and genesis, together with its potential relationship with disuse osteoporosis under simulated microgravity by using a rat tail-suspended model. Sixteen 8-week-old female Sprague-Dawley rats were randomly distributed into control (CON) and tail-suspension (TS) groups. After 21-days of an experiment, fluorescent total AGEs and pentosidine in bone matrix were separately detected by fluorescence microscope and High Performance Liquid Chromatography (HPLC); soluble AGEs and glucose-related biomarkers in serum were detected by ELISA; bone microstructure was evaluated by Micro-CT, and mRNA expression of bone metabolism biomarkers (OCN, ALP, RANKL/OPG) in bone was determined by QPCR. Results showed that after tail-suspension AGEs fluorescent intensity and PEN content increased in trabecular bone while no significant changes in cortical bone; serum glucose increased and was positively correlated with bone matrix AGEs; trabecular bone microstructure was deteriorated, ALP and OCN mRNA expression decreased while RANKL/OPG mRNA expression increased, and all of them showed correlations with bone matrix AGEs. The results suggested under simulated microgravity, bone matrix AGEs accumulation may be attributed to the elevated serum glucose, and preferred to occur in trabecular bone first. AGEs accumulation in bone matrix accompanied negative effects on trabecular bone microstructure and bone metabolism activities under simulated microgravity, suggesting AGEs accumulation may be a culprit in disused bone loss.
•Advanced glycation end products (AGEs) accumulation in tail-suspended rats was correlated with the elevated serum glucose.•Bone matrix AGEs preferentially accumulated in trabecular bone in tail-suspended rats.•AGEs accumulation in bone accompanied negative effects on trabecular bone microstructure and bone metabolism activities.
Many studies have shown that the space environment plays a pivotal role in changing the characteristics of conditional pathogens, especially their pathogenicity and virulence. However,
...Stenotrophomonas maltophilia
, a type of conditional pathogen that has shown to a gradual increase in clinical morbidity in recent years, has rarely been reported for its impact in space. In this study,
S. maltophilia
was exposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14days, while the control group was exposed to the same bioreactors in a normal gravity (NG) environment. Then, combined phenotypic, genomic, transcriptomic, and proteomic analyses were conducted to compare the influence of the SMG and NG on
S. maltophilia
. The results showed that
S. maltophilia
in simulated microgravity displayed an increased growth rate, enhanced biofilm formation ability, increased swimming motility, and metabolic alterations compared with those of
S. maltophilia
in normal gravity and the original strain of
S. maltophilia
. Clusters of Orthologous Groups (COG) annotation analysis indicated that the increased growth rate might be related to the upregulation of differentially expressed genes (DEGs) involved in energy metabolism and conversion, secondary metabolite biosynthesis, transport and catabolism, intracellular trafficking, secretion, and vesicular transport. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the increased motility might be associated the upregulation of differentially expressed proteins (DEPs) involved in locomotion, localization, biological adhesion, and binding, in accordance with the upregulated DEGs in cell motility according to COG classification, including pilP, pilM, flgE, flgG, and ronN. Additionally, the increased biofilm formation ability might be associated with the upregulation of DEPs involved in biofilm formation, the bacterial secretion system, biological adhesion, and cell adhesion, which were shown to be regulated by the differentially expressed genes (chpB, chpC, rpoN, pilA, pilG, pilH, and pilJ) through the integration of transcriptomic and proteomic analyses. These results suggested that simulated microgravity might increase the level of corresponding functional proteins by upregulating related genes to alter physiological characteristics and modulate growth rate, motility, biofilm formation, and metabolism. In conclusion, this study is the first general analysis of the phenotypic, genomic, transcriptomic, and proteomic changes in
S. maltophilia
under simulated microgravity and provides some suggestions for future studies of space microbiology.
In recent years, the successful construction of tissues derived from established iPSCs has been disclosed, but it has been reported that the constructed tissues encounter problems of internal ...necrosis when their size increases. To solve this problem, a simulated microgravity device is used. However, the culture of early developing kidney cells using this device has not yet been reported. This study investigated whether developing kidney cells cultured in a simulated microgravity environment can differentiate into glomerular cells and renal epithelial cells.
The results showed that both mouse developing kidney cells cultured in simulated microgravity and static environment formed kidney spheroids. In static culture, ureteric bud and glomerular structures were not found. While ureteric buds, podocytes, PECAM-1 positive cell aggregates, and primordial vascular plexus were formed in the kidney spheroids in simulated microgravity culture. Moreover, the expression level of the PECAM-1 gene was significant in simulated microgravity culture as compared to that of static culture. These results indicate that simulated microgravity is effective for the differentiation of developing kidney cells.
•Early developing kidney cells were cultured under microgravity, and kidney spheroids were formed within 8 days.•The functional structures such as ureteric buds and glomerular-like tissues were formed within the kidney spheroids.•It has the potential to differentiate of the undifferentiated kidney cells into functional tissue structures.
PDF
