Rapid bone loss exposed to spaceflight is one of the highest risk factors for astronauts which can increase the occurrence of fracture risk and lead to serious health problems, but the therapeutic ...effects of the current countermeasures still have certain limitations and deficiencies. This study aims to find novel potential drugs for the prevention of the bone loss caused by microgravity. Therefore, the systems pharmacology was utilized to discover the active natural compound formononetin in Radix Astragali as the potential drug for the prevention of bone loss. Further, we investigated the therapeutic effects of formononetin in the prevention of bone loss induced by microgravity. Here, the hind limb unloading (HLU) rats’ model was established to simulate the weightlessness, and the HLU rats were treated with formononetin (30 mg· kg−1·day−1) for 4 weeks. The results showed that formononetin treatment clearly ameliorated the microstructure of the trabecular bone, accelerated bone mineral apposition rate and increased bone mineral density, additionally improving biomechanical properties of the bone. Furthermore, the results of the bone turnover biomarkers in serum indicated that formononetin administration effectively decreased the levels of both the bone formation biomarkers and bone resorption biomarkers. In addition, we observed the levels of bone remodeling cytokines including IFN-γ, IL-6, IL-8, IL-12, IL-4, IL-10 and TNF-α were partially recovered by formononetin administration. All of the above indicated that formononetin administration could prevent bone loss induced by HLU treatment due to its ability to inhibit bone turnover and regulate bone remodeling cytokines. These results may contribute to elucidate the novel effects of formononetin against bone loss and further illustrate its potential application value as a leading compound in drug development.
•Formononetin administration ameliorated bone loss induced by HLU treatment.•Formononetin inhibited the high bone turnover and partially reversed the bone remodeling cytokines induced by HLU.•Providing a novel natural product for the treatment of bone loss exposed to simulate microgravity.
Tuber formation in potato (Solanum tuberosum L.) under hypergravity conditions in a centrifuge and simulated microgravity (μG) conditions on a horizontal clinostat was studied using in vitro culture ...of single-nodal stem segments prepared from sprouting tuber shoots. Hypergravity conditions at 100 G for 6 days reduced the growth of axillary bud (or stolon) of a single-nodal stem segment; the length, diameter, and fresh weight of the stolon developed under hypergravity conditions were 53%, 66%, and 74% of 1 G control, respectively. Promotion of swelling seen in the shoot under hypergravity conditions was not observed in the stolon. The size of cells and starch grains in the epidermal tissues in the swelling stolon were reduced under hypergravity conditions. On the other hand, the length of the stolon and the size of the tuber developed in the single-nodal stem segment under simulated μG conditions on a horizontal clinostat for 3 weeks were significantly increased as compared with the 1 G control. These results suggest that stolon growth and tuber formation in the single-nodal stem segment are under the control of gravity. Further studies on the molecular mechanism how gravity regulates tuber development and starch synthesis will be required for increasing potato tuber production in space.
To date, crystallization studies conducted in space laboratories, which are prohibitively costly and unsuitable to most research laboratories, have shown the valuable effects of microgravity during ...crystal growth and morphogenesis. Herein, an easy and highly efficient method is shown to achieve space‐like experimentation conditions on Earth employing custom‐made microfluidic devices to fabricate 2D porous crystalline molecular frameworks. It is confirmed that experimentation under these simulated microgravity conditions has unprecedented effects on the orientation, compactness and crack‐free generation of 2D porous crystalline molecular frameworks as well as in their integration and crystal morphogenesis. It is believed that this work will provide a new “playground” to chemists, physicists, and materials scientists that desire to process unprecedented 2D functional materials and devices.
How to achieve simulated microgravity conditions on Earth? The art of growing and processing 2D porous crystalline molecular frameworks in simulated microgravity is presented.
Abstract Emerging evidence indicates that microRNAs (miRNAs) play important roles in modulating osteoblast function and bone formation. However, the influence of miRNA on osteoblast proliferation and ...the possible mechanisms underlying remain to be defined. In this study, we aimed to investigate whether miR-103 regulates osteoblast proliferation under simulated microgravity condition through regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium channels (LTCCs). We first investigated the effect of simulated microgravity on osteoblast proliferation and the outcomes clearly demonstrated that the mechanical unloading inhibits MC3T3-E1 osteoblast-like cell proliferation. Using quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was up-regulated in response to simulated microgravity. In addition, we observed that up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted osteoblast proliferation under simulated microgravity condition. Furthermore, knocking-down or over-expressing miR-103, respectively, up- or down-regulated the level of Cav1.2 expression and LTCC currents, suggesting that miR-103 acts as an endogenous attenuator of Cav1.2 in osteoblasts under simulated microgravity condition. More importantly, we showed that the effect of miR-103 on osteoblast proliferation was diminished in simulated microgravity, when co-transfecting miR-103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2 expression under simulated microgravity condition. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblast proliferation, identifying miR-103 as a novel possible therapeutic target in bone remodeling disorders in this mechanical unloading.
Affected by the microgravity, astronauts will experience physiological discomfort in spaceflight, leading to an impaired ability of thermoregulation and deteriorating the mentality and operational ...performance of astronauts. It is significant to research on the thermophysiological and psychological phenomena in microgravity for the improvement of the astronauts' long-term comfort in orbit and out of the cabin.
This study aims to explore the effects of microgravity on human thermophysiology and psychology, as well as the correlation between the two indexes, so as to provide a theoretical basis for the thermal control system and mental health protection in space suits and space stations.
The sublingual temperature, local skin temperatures and anxiety-depression psychological indexes of 12 subjects in a stable thermal environment were monitored. The experimental period was 29 days, in which the first 7 days were for the adaptation and basic data collection, the following 15 days were for −6° head down bed rest (HDBR), and the last 7 days after getting up were for the recovery and physical examination. The thermophysiological and psychological indexes were measured on the 4th day before HDBR, the 1st, 5th, 9th, 13th day during HDBR and the 2nd day after HDBR. The temperatures were measured three times one day (morning, noon and evening).
The duration of HDBR had significant effects on the sublingual temperature (p = 0.017) and the weighted average skin temperature (p = 0.014), while the effect on anxiety is marginally significant (p = 0.065). Anxiety and depression scale scores are significantly correlated in simulated microgravity (p = 0.016), while no significant correlation is found between the sublingual temperature and anxiety-depression scale scores (p > 0.05), nor the weighted average skin temperature and anxiety-depression scale scores (p > 0.05). The back skin temperature and the anxiety score are significantly correlated in simulated microgravity (p = 0.012).
The peak of anxiety and depression in the early stage of HDBR appeared on the 5th day. Thermophysiological and psychological adaptation occurred in the middle period, with values recovering to the initial levels in the later stage and after HDBR. This study could support the improvement of the thermal control system in space suits and space stations, and the protection of astronauts' mental health. A larger set of subjects and a longer experimental period could be considered in the future research, exploring more precise and complete principles of human thermophysiological and psychological changes in simulated microgravity.
•The duration of HDBR had significant effects on the sublingual temperature.•The duration of HDBR had significant effects on the weighted average skin temperature.•The duration of HDBR had marginally significant effects on the anxiety scale score.•Anxiety and depression scale scores are significantly correlated in simulated microgravity.•The back skin temperature and the anxiety score are significantly correlated in simulated microgravity.
Purpose: The rotary cell culture system (RCCS) is a common clinorotation device for cell culture. It is also used as a low-shear suspension culture bioreactor to form functionalized 3D tissue ...constructs and to model microgravity. We sought to develop a 3D scaffold composed of type I collagen and hydroxyapatite (collagen-HA) to characterize MLO-Y4 osteocytes following suspension culture or clinorotation.
Materials and Methods: MLO-Y4 cells were embedded in collagen-HA. The scaffold was formed into droplets for suspension culture or wall-adhered to the RCCS for clinorotation. AFM, rheometry, immunofluorescence and qRT-PCR were employed to measure the scaffold stiffness, cell viability and gene expression of cells in collagen-HA scaffolds. Dendritic cells were visualized and quantified and gene expression after suspension culture and clinorotation was compared to static controls.
Results: The optimized scaffold for the RCCS consisted of collagen with 6 mg/mL HA which had a stiffness of < 1 kPa. MLO-Y4 cell viability was higher in collagen-HA scaffolds, compared to scaffolds without HA. Collagen-HA scaffolds induced higher osteocyte-specific gene expression compared to cells cultured on 2D plastic. Cells in the scaffold downregulated DMP1, E11, IL-6, and RANKL, and had fewer dendritic cells following suspension culture whereas clinorotation downregulated DMP1 and E11 genes, compared to static controls.
Conclusions: Suspension culture for 3 days in collagen-HA stimulates growth of osteocytes but may also desensitize them to mechanical cues. Clinorotation for 3 days in collagen-HA does not stimulate proliferation or expression of mechanosensitive genes, indicating that it may be an effective mechanical unloading environment.
An organoid is a 3D organization of cells that can recapitulate some of the structure and function of native tissue. Recent work has seen organoids gain prominence as a valuable model for studying ...tissue development, drug discovery, and potential clinical applications. The requirements for the successful culture of organoids in vitro differ significantly from those of traditional monolayer cell cultures. The generation and maturation of high-fidelity organoids entails developing and optimizing environmental conditions to provide the optimal cues for growth and 3D maturation, such as oxygenation, mechanical and fluidic activation, nutrition gradients, etc. To this end, we discuss the four main categories of bioreactors used for organoid culture: stirred bioreactors (SBR), microfluidic bioreactors (MFB), rotating wall vessels (RWV), and electrically stimulating (ES) bioreactors. We aim to lay out the state-of-the-art of both commercial and in-house developed bioreactor systems, their benefits to the culture of organoids derived from various cells and tissues, and the limitations of bioreactor technology, including sterilization, accessibility, and suitability and ease of use for long-term culture. Finally, we discuss future directions for improvements to existing bioreactor technology and how they may be used to enhance organoid culture for specific applications.
Venoconstrictive thigh cuffs are used by cosmonauts to ameliorate symptoms associated with cephalad fluid shift. A ground simulation of microgravity, using the dry immersion (DI) model, was performed ...to assess the effects of thigh cuffs on body fluid changes and dynamics, as well as on cardiovascular deconditioning. Eighteen healthy men (25-43 years), randomly divided into two groups, (1) control group or (2) group with thigh cuffs worn 10 h/day, underwent 5-day DI. Cardiovascular responses to orthostatic challenge were evaluated using the lower body negative pressure (LBNP) test; body fluid changes were assessed by bio-impedance and hormonal assay; plasma volume evolution was estimated using hemoglobin-hematocrit; subjective tolerance was assessed by questionnaires. DI induced a decrease in plasma volume of 15-20%. Reduction in total body water of 3-6% stabilized toward the third day of DI. This reduction was derived mostly from the extracellular compartment. During the acute phase of DI, thigh cuffs limited the decrease in renin and the increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), the loss in total body water, and tended to limit the loss in calf volume, extracellular volume and plasma volume. At the later stable phase of DI, a moderate protective effect of thigh cuffs remained evident on the body fluids. Orthostatic tolerance time dropped after DI without significant difference between groups. Thigh cuff countermeasure slowed down and limited the loss of body water and tended to limit plasma loss induced by DI. These observed physiological responses persisted during periods when thigh cuffs were removed. However, thigh cuffs did not counteract decreased tolerance to orthostatic challenge.
Breast cancer is the most commonly occurring cancer in women and impacts around 2.1 million women each year. The drug treatment depends on the type of breast cancer and severity of disease. But, ...continuous use of drugs often leads to resistance and thus need arises for development of newer drugs. In order to find out the alternative treatment strategies, the breast cancer cells are analysed for their behaviour in different conditions. Microgravity is one such strategy currently being studied. Both cancerous and non-cancerous cells behave differently in absence of gravity. So, it could be speculated that microgravity might be a complementary tool for future cancer treatment and may open a new window for clinical cancer therapies. In this review, we summarise the effect of microgravity on breast cancer cells as well as anticancer drugs for breast cancer treatment, drugs in preclinical and clinical phases. We believe that this review will provide a comprehensive report on many aspects of breast cancer research and help to establish the therapeutic links between microgravity and breast cancer treatment.
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•Breast cancer is the most widely occurring cancer in women and overall ranks 5th in terms of cancer related mortalities.•Though a large number of drugs are available for treatment of breast cancer, prolong use of drugs leads to resistance and side effects.•In order to improve the efficacy of the drugs, new strategies like microgravity is being studied for future cancer treatment.•Microgravity or absence of gravity leads to certain changes in the normal and cancerous cells and can be exploited as a potential complementary tool for breast cancer treatment.
A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated ...neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight exposed samples. To assess mechanisms involved, we found the simulated microgravity HARV-RWV model resulted in an imbalance of redox processes and activation of myeloperoxidase-producing inflammatory neutrophils, while antioxidant treatment reversed these effects. In the simulated microgravity HU model, mitochondrial catalase-transgenic mice that have reduced oxidative stress responses showed reduced neutrophil counts, NLR, and a dampened release of selective inflammatory cytokines compared to wildtype HU mice, suggesting simulated microgravity induced oxidative stress responses that triggered inflammation. In brief, both spaceflight and simulated microgravity models caused elevated NLR, indicating this as a potential biomarker for future in-flight immune health monitoring.
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