scholarly journals Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro

2020 ◽  
Vol 21 (24) ◽  
pp. 9373
Author(s):  
Binod Prasad ◽  
Daniela Grimm ◽  
Sebastian M. Strauch ◽  
Gilmar Sidnei Erzinger ◽  
Thomas J. Corydon ◽  
...  
Keyword(s):  
Cosmic Radiation ◽  
Current Knowledge ◽  
Life Forms ◽  
Model Systems ◽  
Space Environment ◽  
Cellular Damage ◽  
The Impact ◽  
In Cells

All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage. Space environmental conditions have been shown to influence apoptosis in various cell types. Apoptosis has important functions in morphogenesis, organ development, and wound healing. This review provides an overview of microgravity research platforms and apoptosis. The sections summarize the current knowledge of the impact of microgravity and cosmic radiation on cells with respect to apoptosis. Apoptosis-related microgravity experiments conducted with different mammalian model systems are presented. Recent findings in cells of the immune system, cardiovascular system, brain, eyes, cartilage, bone, gastrointestinal tract, liver, and pancreas, as well as cancer cells investigated under real and simulated microgravity conditions, are discussed. This comprehensive review indicates the potential of the space environment in biomedical research.

scholarly journals Exposure to airborne gold nanoparticles: a review of current toxicological data on the respiratory tract

2020 ◽  
Vol 22 (8) ◽  
Author(s):  
Barbara De Berardis ◽  
Magda Marchetti ◽  
Anna Risuglia ◽  
Federica Ietto ◽  
Carla Fanizza ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Human Health ◽  
Large Scale ◽  
Current Knowledge ◽  
Engineered Nanoparticles ◽  
In Vivo Studies ◽  
Field Exposure ◽  
The Impact

AbstractIn recent years, the introduction of innovative low-cost and large-scale processes for the synthesis of engineered nanoparticles with at least one dimension less than 100 nm has led to countless useful and extensive applications. In this context, gold nanoparticles stimulated a growing interest, due to their peculiar characteristics such as ease of synthesis, chemical stability and optical properties. This stirred the development of numerous applications especially in the biomedical field. Exposure of manufacturers and consumers to industrial products containing nanoparticles poses a potential risk to human health and the environment. Despite this, the precise mechanisms of nanomaterial toxicity have not yet been fully elucidated. It is well known that the three main routes of exposure to nanomaterials are by inhalation, ingestion and through the skin, with inhalation being the most common route of exposure to NPs in the workplace. To provide a complete picture of the impact of inhaled gold nanoparticles on human health, in this article, we review the current knowledge about the physico-chemical characteristics of this nanomaterial, in the size range of 1–100 nm, and its toxicity for pulmonary structures both in vitro and in vivo. Studies comparing the toxic effect of NPs larger than 100 nm (up to 250 nm) are also discussed.

scholarly journals EGFRAmplification and Glioblastoma Stem-Like Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Katrin Liffers ◽  
Katrin Lamszus ◽  
Alexander Schulte
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Current Knowledge ◽  
Growth Factor Receptor ◽  
Model Systems ◽  
Preclinical Research ◽  
Epidermal Growth ◽  
Methodological Approaches ◽  
The Impact

Glioblastoma (GBM), the most common malignant brain tumor in adults, contains a subpopulation of cells with a stem-like phenotype (GS-cells). GS-cells can be maintainedin vitrousing serum-free medium supplemented with epidermal growth factor, basic fibroblast growth factor-2, and heparin. However, this method does not conserve amplification of the Epidermal Growth Factor Receptor (EGFR) gene, which is present in over 50% of all newly diagnosed GBM cases. GS-cells with retainedEGFRamplification could overcome the limitations of currentin vitromodel systems and contribute significantly to preclinical research on EGFR-targeted therapy. This review recapitulates recent methodological approaches to expand stem-like cells from GBM with differentEGFRstatus in order to maintain EGFR-dependent intratumoral heterogeneityin vitro. Further, it will summarize the current knowledge about the impact ofEGFRamplification and overexpression on the stem-like phenotype of GBM-derived GS-cells and different approaches to target the EGFR-dependent GS-cell compartment of GBM.

scholarly journals A Mouse Model Of Binge Alcohol Consumption andBurkholderiaInfection

2018 ◽  
Author(s):  
Victor Jimenez ◽  
Ryan Moreno ◽  
Erik Settles ◽  
Bart J Currie ◽  
Paul Keim ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Binge Drinking ◽  
Burkholderia Pseudomallei ◽  
Alcohol Exposure ◽  
Model Systems ◽  
Phagocytic Cells ◽  
Intracellular Invasion ◽  
The Impact

AbstractBackgroundBinge drinking, a common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood.Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure results in reduced alveolar macrophage function and increasedBurkholderiavirulencein vitro, no experimental studies have investigated the outcomes of binge alcohol onBurkholderiaspp. infectionin vivo.Principal FindingsWe used the close genetic relatives ofB. pseudomallei, B. thailandensisE264 andB. vietnamiensis, as useful BSL-2 model systems. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking episodes (4.4 g/kg) or PBS intraperitoneally 30 min before a non-lethal intranasal infection. In an initialB. thailandensisinfection (3 x 105), bacteria accumulated in the lungs and disseminated to the spleen in alcohol administered mice only, compared with PBS treated mice at 24 h post-infection (PI). The greatest bacterial load occurred withB. vietnamiensis(1 x 106) in lungs, spleen, and brain tissue by 72 h PI. Pulmonary cytokine expression (TNF-α, GM-CSF) decreased, while splenic cytokine (IL-10) increased in binge drunk mice. Increased lung and brain permeability was observed as early as 2 h post alcohol administrationin vivo.Trans-epithelial electrical resistance (TEER) was significantly decreased, while intracellular invasion of non-phagocytic cells increased with 0.2% v/v alcohol exposurein vitro.ConclusionsOur results indicate that a single binge alcohol dose suppressed innate immune functions and increased the ability of less virulentBurkholderiastrains to disseminate through increased barrier permeability and intracellular invasion of non-phagocytic cells.Author SummaryBurkholderia pseudomalleicauses the disease melioidosis, which occurs in most tropical regions across the globe. Exposure rarely evolves to significant disease in the absence of specific comorbidities, such as binge alcohol intoxication. In susceptible hosts, the disease is primarily manifested as pneumonic melioidosis and can be rapidly fatal if untreated. In this study, we utilizedB. thailandensis, a genetically similar strain toB. pseudomallei, and opportunisticB. vietnamiensis, a known human pathogen that utilizes similar virulence strategies asB. pseudomalleiin immunocompromised and cystic fibrosis patients. The study investigates the impact of a single binge alcohol episode on infectivity and immune responsein vivo. We show that a single binge alcohol episode prior to inhalingBurkholderiaspecies increases bacterial spread to the lungs and brain. We also identify alcohol-induced tissue permeability and epithelial cell invasion as modes of action for greater bacterial spread and survival inside the host. Our results support the public health responses being developed in melioidosis-endemic regions that emphasize the nature of binge drinking as a prime concern, especially around potential times of exposure to environmentalB. pseudomallei.

scholarly journals Optical flow analysis reveals that Kinesin-mediated advection impacts on the orientation of microtubules in the Drosophila oocyte

2019 ◽  
Author(s):  
Maik Drechsler ◽  
Lukas F. Lang ◽  
Layla Al-Khatib ◽  
Hendrik Dirks ◽  
Martin Burger ◽  
...  
Keyword(s):  
Optical Flow ◽  
Cytoplasmic Streaming ◽  
Flow Analysis ◽  
Growth Direction ◽  
Model Systems ◽  
Microtubule Orientation ◽  
A Cell ◽  
The Impact

ABSTRACTThe orientation of microtubule networks is exploited by motors to deliver cargoes to specific intracellular destinations, and is thus essential for cell polarity and function. Reconstituted in vitro systems have largely contributed to understanding the molecular framework regulating the behavior of microtubule filaments. In cells however, microtubules are exposed to various biomechanical forces that might impact on their orientation, but little is known about it. Oocytes, which display forceful cytoplasmic streaming, are excellent model systems to study the impact of motion forces on cytoskeletons in vivo. Here we implement variational optical flow analysis as a new approach to analyze the polarity of microtubules in the Drosophila oocyte, a cell that displays distinct Kinesin-dependent streaming. After validating the method as robust for describing microtubule orientation from confocal movies, we find that increasing the speed of flows results in aberrant plus end growth direction. Furthermore, we find that in oocytes where Kinesin is unable to induce cytoplasmic streaming, the growth direction of microtubule plus ends is also altered. These findings lead us to propose that cytoplasmic streaming - and thus motion by advection – contributes to the correct orientation of MTs in vivo. Finally, we propose a possible mechanism for a specialised cytoplasmic actin network (the actin mesh) to act as a regulator of flow speeds; to counteract the recruitment of Kinesin to microtubules.HIGHLIGHT SUMMARYCytoskeletal networks do not exist in isolation, but experience crowded and dynamic intracellular environments. However, microtubule-environment interactions are not well understood, and such system-environment interactions are an unresolved question in biology that demands bridging across disciplines. Here we introduce an optical flow motion estimation approach to study microtubule orientation in the Drosophila oocyte, a cell displaying substantial cytoplasmic streaming. We show that microtubule polarity is affected by the regime of these flows, and furthermore, that the presence of flows is necessary for MTs to adopt their proper polarity. With these findings we are contributing to further understanding how microtubules organize in their impacting natural environment.

scholarly journals Ursolic and Oleanolic Acids: Plant Metabolites with Neuromodulatory Potential

2021 ◽  
Author(s):  
Evelina Gudoityte ◽  
Odeta Arandarcikaite ◽  
Ingrida Mazeikiene ◽  
Vidmantas Bendokas ◽  
Julius Liobikas
Keyword(s):  
Current Knowledge ◽  
Plant Defence ◽  
Model Systems ◽  
Animal Origin ◽  
Antioxidant Systems ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Beneficial Effects

Ursolic and oleanolic acids are secondary plant metabolites that are known to be involved in the plant defence system against water loss and pathogens. Nowadays these triterpenoids are also regarded as potential pharmaceutical compounds and there is mounting experimental data that either purified compounds or triterpenoid-enriched plant extracts exert various beneficial effects, including anti-oxidative, anti-inflammatory and anticancer, on model systems of both human or animal origin. Some of those effects have been linked to the ability of ursolic and oleanolic acids to modulate intracellular antioxidant systems and also inflammation- and cell death-related pathways. Therefore, our aim was to review the current knowledge about the distribution of ursolic and oleanolic acids in plants, bioavailability and pharmacokinetic properties of these triterpenoids and their derivatives, and to discuss their neuromodulatory effects in vitro and in vivo.

scholarly journals Between Fate Choice and Self-Renewal—Heterogeneity of Adult Neural Crest-Derived Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Anna L. Höving ◽  
Beatrice A. Windmöller ◽  
Cornelius Knabbe ◽  
Barbara Kaltschmidt ◽  
Christian Kaltschmidt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Crest ◽  
Current Knowledge ◽  
Mapk Signaling ◽  
Cellular Heterogeneity ◽  
Self Renewal ◽  
The Impact

Stem cells of the neural crest (NC) vitally participate to embryonic development, but also remain in distinct niches as quiescent neural crest-derived stem cell (NCSC) pools into adulthood. Although NCSC-populations share a high capacity for self-renewal and differentiation resulting in promising preclinical applications within the last two decades, inter- and intrapopulational differences exist in terms of their expression signatures and regenerative capability. Differentiation and self-renewal of stem cells in developmental and regenerative contexts are partially regulated by the niche or culture condition and further influenced by single cell decision processes, making cell-to-cell variation and heterogeneity critical for understanding adult stem cell populations. The present review summarizes current knowledge of the cellular heterogeneity within NCSC-populations located in distinct craniofacial and trunk niches including the nasal cavity, olfactory bulb, oral tissues or skin. We shed light on the impact of intrapopulational heterogeneity on fate specifications and plasticity of NCSCs in their niches in vivo as well as during in vitro culture. We further discuss underlying molecular regulators determining fate specifications of NCSCs, suggesting a regulatory network including NF-κB and NC-related transcription factors like SLUG and SOX9 accompanied by Wnt- and MAPK-signaling to orchestrate NCSC stemness and differentiation. In summary, adult NCSCs show a broad heterogeneity on the level of the donor and the donors’ sex, the cell population and the single stem cell directly impacting their differentiation capability and fate choices in vivo and in vitro. The findings discussed here emphasize heterogeneity of NCSCs as a crucial parameter for understanding their role in tissue homeostasis and regeneration and for improving their applicability in regenerative medicine.

Investigating the Biological and Molecular Mechanisms Underpinning the Engraftment/Selection Advantage Conferred to Hematopoietic Stem Cells by HOXB4.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2101-2101
Author(s):  
Michael D. Milsom ◽  
Laura Hollins ◽  
Dorothy Gagen ◽  
Lorna B. Woolford ◽  
Leslie J. Fairbairn
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cellular Transformation ◽  
Model Systems ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Vitro Analysis

Abstract We have recently demonstrated that co-expression of HOXB4 enables the enhanced delivery of HSC harbouring a second therapeutic trans-gene. Nonetheless, it is of great importance to elaborate the current knowledge about the mechanism of HOXB4 action in order to both evaluate the safety implications of its use in a clinical strategy, and to gain greater insight into the regulation of HSC self-renewal/expansion. To these ends we have performed an extensive in vitro analysis of the consequences of HOXB4 overexpression in primary murine BMC and in a murine multipotent myeloid progenitor cell line (FDCP-mix). We demonstrate for the first time in murine cells, that ectopic HOXB4 reduces the responsiveness of murine hematopoietic cells to differentiation stimuli. Furthermore, by performing a detailed investigation into the kinetics of FDCP-mix differentiation, we reveal that HOXB4 overexpression results in a specific differentiation delay as opposed to an outright block. We propose that an analogous delay is in operation in repopulating cells in order that the shift to increased assymetrical self-renewal, a requirement for stem cell expansion, is achieved. Notwithstanding this, it is clear that any perturbation in differentiation constitutes an increased risk of cellular transformation if this technology were transferred to a clinical setting. In order to further define the repercussions of ectopic HOXB4 delivery, we have developed a retroviral vector which encodes an activatable version of HOXB4. We have shown that this vector is able to mediate an in vitro differentiation delay in primary murine BMC and FDCP-mix as well as enable enhanced engraftment of BMC in vivo, both dependent upon the addition of the estrogen analogue; tamoxifen. Using this system, we are currently examining the effect of ectopic HOXB4 on the transcriptome of FDCP-mix cells, in addition to performing an in depth study into the biological mechanisms affected by HOXB4 overexpression in BMC in vivo. We envisage that these model systems will be particularly amenable to the manipulation required for target gene identification/validation.

scholarly journals The Impact of Acute or Chronic Alcohol Intake on the NF-κB Signaling Pathway in Alcohol-Related Liver Disease

2020 ◽  
Vol 21 (24) ◽  
pp. 9407
Author(s):  
Aleksander J. Nowak ◽  
Borna Relja
Keyword(s):  
Liver Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Related Liver Disease ◽  
The Impact

Ethanol misuse is frequently associated with a multitude of profound medical conditions, contributing to health-, individual- and social-related damage. A particularly dangerous threat from this classification is coined as alcoholic liver disease (ALD), a liver condition caused by prolonged alcohol overconsumption, involving several pathological stages induced by alcohol metabolic byproducts and sustained cellular intoxication. Molecular, pathological mechanisms of ALD principally root in the innate immunity system and are especially associated with enhanced functionality of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. NF-κB is an interesting and convoluted DNA transcription regulator, promoting both anti-inflammatory and pro-inflammatory gene expression. Thus, the abundancy of studies in recent years underlines the importance of NF-κB in inflammatory responses and the mechanistic stimulation of inner molecular motifs within the factor components. Hereby, in the following review, we would like to put emphasis on the correlation between the NF-κB inflammation signaling pathway and ALD progression. We will provide the reader with the current knowledge regarding the chronic and acute alcohol consumption patterns, the molecular mechanisms of ALD development, the involvement of the NF-κB pathway and its enzymatic regulators. Therefore, we review various experimental in vitro and in vivo studies regarding the research on ALD, including the recent active compound treatments and the genetic modification approach. Furthermore, our investigation covers a few human studies.

scholarly journals The Impact of CRISPR/Cas9 Technology on Cardiac Research: From Disease Modelling to Therapeutic Approaches

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Benedetta M. Motta ◽  
Peter P. Pramstaller ◽  
Andrew A. Hicks ◽  
Alessandra Rossini
Keyword(s):  
Genome Editing ◽  
Ethical Issues ◽  
Therapeutic Potential ◽  
Gene Knockout ◽  
Model Systems ◽  
Large Deletions ◽  
Induced Pluripotent ◽  
The Impact

Genome-editing technology has emerged as a powerful method that enables the generation of genetically modified cells and organisms necessary to elucidate gene function and mechanisms of human diseases. The clustered regularly interspaced short palindromic repeats- (CRISPR-) associated 9 (Cas9) system has rapidly become one of the most popular approaches for genome editing in basic biomedical research over recent years because of its simplicity and adaptability. CRISPR/Cas9 genome editing has been used to correct DNA mutations ranging from a single base pair to large deletions in both in vitro and in vivo model systems. CRISPR/Cas9 has been used to increase the understanding of many aspects of cardiovascular disorders, including lipid metabolism, electrophysiology and genetic inheritance. The CRISPR/Cas9 technology has been proven to be effective in creating gene knockout (KO) or knockin in human cells and is particularly useful for editing induced pluripotent stem cells (iPSCs). Despite these progresses, some biological, technical, and ethical issues are limiting the therapeutic potential of genome editing in cardiovascular diseases. This review will focus on various applications of CRISPR/Cas9 genome editing in the cardiovascular field, for both disease research and the prospect of in vivo genome-editing therapies in the future.

scholarly journals The Impact of Microgravity on Bone Metabolism in vitro and in vivo

2001 ◽  
Vol 12 (3) ◽  
pp. 252-261 ◽  
Author(s):  
Peter M. Loomer
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Metabolism ◽  
Bone Cells ◽  
Mechanical Load ◽  
Space Environment ◽  
In Vivo Studies ◽  
The Impact

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.

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