The Future of Personalized Medicine in Space: From Observations to Countermeasures

The aim of personalized medicine is to detach from a “one-size fits all approach” and improve patient health by individualization to achieve the best outcomes in disease prevention, diagnosis and treatment. Technological advances in sequencing, improved knowledge of omics, integration with bioinformatics and new in vitro testing formats, have enabled personalized medicine to become a reality. Individual variation in response to environmental factors can affect susceptibility to disease and response to treatments. Space travel exposes humans to environmental stressors that lead to physiological adaptations, from altered cell behavior to abnormal tissue responses, including immune system impairment. In the context of human space flight research, human health studies have shown a significant inter-individual variability in response to space analogue conditions. A substantial degree of variability has been noticed in response to medications (from both an efficacy and toxicity perspective) as well as in susceptibility to damage from radiation exposure and in physiological changes such as loss of bone mineral density and muscle mass in response to deconditioning. At present, personalized medicine for astronauts is limited. With the advent of longer duration missions beyond low Earth orbit, it is imperative that space agencies adopt a personalized strategy for each astronaut, starting from pre-emptive personalized pre-clinical approaches through to individualized countermeasures to minimize harmful physiological changes and find targeted treatment for disease. Advances in space medicine can also be translated to terrestrial applications, and vice versa. This review places the astronaut at the center of personalized medicine, will appraise existing evidence and future preclinical tools as well as clinical, ethical and legal considerations for future space travel.

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The Cardiovascular System in Space: Focus on In Vivo and In Vitro Studies

Biomedicines ◽

10.3390/biomedicines10010059 ◽

2021 ◽

Vol 10 (1) ◽

pp. 59

Author(s):

Ronni Baran ◽

Shannon Marchal ◽

Sebastian Garcia Campos ◽

Emil Rehnberg ◽

Kevin Tabury ◽

...

Keyword(s):

Cellular Proliferation ◽

Orthostatic Intolerance ◽

Underlying Mechanism ◽

Low Earth Orbit ◽

Molecular Changes ◽

Human Spaceflight ◽

Altered Cell ◽

And Function

On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to orthostatic intolerance. This review summarises all known cardiovascular diseases related to human spaceflight and focusses on the cardiovascular changes related to human spaceflight (in vivo) as well as cellular and molecular changes (in vitro). Upon entering microgravity, cephalad fluid shift occurs and increases the stroke volume (35–46%) and cardiac output (18–41%). Despite this increase, astronauts enter a state of hypovolemia (10–15% decrease in blood volume). The absence of orthostatic pressure and a decrease in arterial pressures reduces the workload of the heart and is believed to be the underlying mechanism for the development of cardiac atrophy in space. Cellular and molecular changes include altered cell shape and endothelial dysfunction through suppressed cellular proliferation as well as increased cell apoptosis and oxidative stress. Human spaceflight is associated with several cardiovascular risk factors. Through the use of microgravity platforms, multiple physiological changes can be studied and stimulate the development of appropriate tools and countermeasures for future human spaceflight missions in low Earth orbit and beyond.

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Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

Scientific Reports ◽

10.1038/s41598-021-84620-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adriana M. De Mendoza ◽

Soňa Michlíková ◽

Johann Berger ◽

Jens Karschau ◽

Leoni A. Kunz-Schughart ◽

...

Keyword(s):

Protein Denaturation ◽

Collateral Damage ◽

Hyperthermia Treatment ◽

Reversible Process ◽

Technological Advances ◽

Thermal Enhancement ◽

Main Driver ◽

Definition Of

AbstractRadiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

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Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22010233 ◽

2020 ◽

Vol 22 (1) ◽

pp. 233

Author(s):

Eunkuk Park ◽

Chang Gun Lee ◽

Eunguk Lim ◽

Seokjin Hwang ◽

Seung Hee Yun ◽

...

Keyword(s):

Osteoclast Differentiation ◽

Osteoblastic Differentiation ◽

Common Disease ◽

Root Extract ◽

Mouse Bone Marrow ◽

Mineral Density ◽

Bone Mineral Density Loss ◽

In Vivo Experiments

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

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Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System

Journal of Personalized Medicine ◽

10.3390/jpm11060475 ◽

2021 ◽

Vol 11 (6) ◽

pp. 475

Author(s):

Joaquín Dopazo ◽

Douglas Maya-Miles ◽

Federico García ◽

Nicola Lorusso ◽

Miguel Ángel Calleja ◽

...

Keyword(s):

Public Health ◽

Health Care ◽

Clinical Practice ◽

Personalized Medicine ◽

Local Level ◽

Individual Variability ◽

Response To Therapy ◽

Control Measures ◽

Response To Treatment ◽

Specific Patient

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems.

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Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies

Journal of Tissue Engineering ◽

10.1177/2041731420981339 ◽

2021 ◽

Vol 12 ◽

pp. 204173142098133

Author(s):

Juan M. Fernández-Costa ◽

Xiomara Fernández-Garibay ◽

Ferran Velasco-Mallorquí ◽

Javier Ramón-Azcón

Keyword(s):

Skeletal Muscle ◽

Tissue Engineering ◽

Electrical Stimulation ◽

Skeletal Muscles ◽

Screening Tools ◽

Muscular Dystrophies ◽

Preclinical Studies ◽

Technological Advances ◽

Topographical Cues

Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.

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Abnormal physiological properties and altered cell wall composition in Streptococcus pneumoniae grown in the presence of clavulanic acid.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.3.504 ◽

1997 ◽

Vol 41 (3) ◽

pp. 504-510 ◽

Cited By ~ 25

Author(s):

A Severin ◽

E Severina ◽

A Tomasz

Keyword(s):

Streptococcus Pneumoniae ◽

High Performance ◽

Biochemical Properties ◽

Beta Lactam ◽

Chromatography Analysis ◽

Peptide Composition ◽

Increased Sensitivity ◽

Altered Cell ◽

Quantitative Changes

Subinhibitory concentrations of clavulanate caused premature induction of stationary-phase autolysis, sensitization to lysozyme, and reductions in the MICs of deoxycholate and penicillin for Streptococcus pneumoniae. In the range of clavulanate concentrations producing these effects, this beta-lactam compound was selectively bound to PBP 3. Cell walls isolated from pneumococci grown in the presence of clavulanate showed increased sensitivity to the hydrolytic action of purified pneumococcal autolysin in vitro. High-performance liquid chromatography analysis of the peptidoglycan isolated from the clavulanate-grown cells showed major qualitative and quantitative changes in stem peptide composition, the most striking feature of which was the accumulation of peptide species carrying intact D-alanyl-D-alanine residues at the carboxy termini. The altered biological and biochemical properties of the clavulanate-grown pneumococci appear to be the consequences of suppressed D,D-carboxypeptidase activity.

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MiR-206 regulates the progression of osteoporosis via targeting HDAC4

European Journal of Medical Research ◽

10.1186/s40001-021-00480-3 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Zhiyuan Lu ◽

Dawei Wang ◽

Xuming Wang ◽

Jilong Zou ◽

Jiabing Sun ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Diagnostic Value ◽

Expression Level ◽

Luciferase Reporter ◽

Control Group ◽

Luciferase Reporter Gene ◽

Mineral Density ◽

Gene Assay

Abstract Background More and more studies have confirmed that miRNAs play an important role in maintaining bone remodeling and bone metabolism. This study investigated the expression level of miR-206 in the serum of osteoporosis (OP) patients and explored the effect and mechanism of miR-206 on the occurrence and development of osteoporosis. Methods 120 postmenopausal women were recruited, including 63 cases with OP and 57 women without OP. The levels of miR-206 were determined by qRT-PCR technology. Spearman correlation coefficient was used to evaluate the correlation of miR-206 with bone mineral density (BMD). An ROC curve was used to evaluate the diagnostic value of miR-206 in osteoporosis. The effects of miR-206 on cell proliferation and cell apoptosis of hFOBs were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter gene assay was used to confirm the interaction of miR-206 and the 3′UTR of HDAC4. Results Serum miR-206 had low expression level in osteoporosis patient group compared with control group. The expression level of serum miR-206 had diagnostic value for osteoporosis, and the serum miR-206 levels were positively correlated with BMD. The down-regulated miR-206 could inhibit cell proliferation and promote cell apoptosis. Luciferase analysis indicated that HDAC4 was the target gene of miR-206. Conclusions MiR-206 could be used as a new potential diagnostic biomarker for osteoporosis, and in in vitro cell experiments, miR-206 may regulate osteoblast cell proliferation and apoptosis by targeting HDAC4.

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Copper as Dietary Supplement for Bone Metabolism: A Review

Nutrients ◽

10.3390/nu13072246 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2246

Author(s):

Mariangela Rondanelli ◽

Milena Anna Faliva ◽

Vittoria Infantino ◽

Clara Gasparri ◽

Giancarlo Iannello ◽

...

Keyword(s):

Bone Metabolism ◽

Bone Mineral ◽

Animal Studies ◽

Small Sample ◽

Blood Levels ◽

Mineral Density ◽

Dietary Copper ◽

Slowing Down ◽

Copper Supplementation

While in vitro and animal studies of osteoblastic and osteoclastic activity as well as bone resistance for copper are numerous, and the results encouraging in terms of regulation, human studies are scarce. The aim of this narrative review was to investigate the correlation of blood copper, daily copper intake, and copper supplementation with bone mineral density. This review included 10 eligible studies: five studies concerned copper blood levels, one study concerned daily copper intake, and four studies concerned copper supplementation. Blood copper levels did not show statistically significant differences in four of the studies analyzed, while only one study showed differences between osteoporotic and healthy women, although only with women between 45 and 59 years of age and not between 60 and 80 years of age. The dietary copper intake among women with or without osteoporosis did not show any differences. Only one study with a small sample of subjects carried out these assessments; therefore, it is a topic that the literature must deepen with further studies. The two studies that analyzed the integration of copper (2.5–3 mg/day) only showed good results in terms of slowing down bone mineral loss and reducing resorption markers, confirming the effectiveness of copper supplementation on bone metabolism.

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Mineral Density and Fluoride Content of in vitro Remineralized Lesions

Journal of Dental Research ◽

10.1177/00220345880670031001 ◽

1988 ◽

Vol 67 (3) ◽

pp. 577-581 ◽

Cited By ~ 8

Author(s):

Y. Jima ◽

T. Koulourides

Keyword(s):

Complete Recovery ◽

Fluoride Content ◽

Mineral Density ◽

Acid Dissolution ◽

Thin Sections ◽

Partially Saturated ◽

In Vitro Investigation ◽

Bovine Enamel ◽

Caries Lesions

This in vitro investigation studied the remineralization of experimental caries lesions in bovine enamel by use of three methods: (1) surface microhardness, (2) microradiography, and (3) abrasion biopsy for mineral density and fluoride content. The lesions were produced by a two-day exposure to 0.01 mol/L lactic acidlsodium hydroxide buffer partially saturated with 3.0 mmol/L Ca, 1.8 mmol/L P, in 1% CMC, at pH 4.0 and 37°C. The lesions were exposed to a remineralizing solution containing 3.0 mmol/L Ca, 1.8 mmol/L P, and 3 ppm F in 1% CMC at pH 7.0 and 37°C for two, six, and ten days, with solution changes every two days. The data derived from the three methods are presented in sequence from the baseline and at days two, six, and ten of the remineralizing treatment. Microhardness measurements showed hardness recoveries of 35.9, 78.9, and 87.5%, respectively. Microradiography suggested complete recovery with the ten-day remineralization. Abrasion biopsy of successive 10-μm layers to a depth of 100 μm indicated 15.2, 39.8, and 68.8% mineral density recoveries, with fluoride content of the surface layer increasing from a baseline of 300 ppm to 4600, 9000, and 9800 ppm F for the 2, 6, 10 days of remineralization, respectively. Subsequent acid-etching of thin sections from the ten-day-remineralized specimens showed that the fluoride-enriched remineralized area was more resistant to acid dissolution than was the underlying nonnal enamel.

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