scholarly journals Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Shuhua Gao ◽  
Cheng Xiang ◽  
Kairong Qin ◽  
Changkai Sun
Keyword(s):  
Mathematical Modeling ◽  
Transition Rate ◽  
State Transition ◽  
Replicative Senescence ◽  
Experimental Studies ◽  
Human Mesenchymal Stem Cells ◽  
Cellular Division ◽  
Experimental Findings

Many experimental studies have found that human mesenchymal stem cells (MSCs) in long-term culture exhibited enhanced cell proliferation and prolonged lifespan under hypoxia (around 1%–7% oxygen) against the normoxic condition (about 21% oxygen). Inspired by the experimental findings, we aimed to investigate the hypoxic effects on MSC expansion quantitatively through mathematical modeling to elucidate the corresponding biological mechanism. A two-compartment model based on ordinary differential equations (ODEs), which incorporate cellular division and senescence via state transition, was developed to describe the MSC expansion process. Parameters of this model were fitted to experimental data and used to interpret the different proliferative capacities of MSCs under hypoxia and normoxia along with model sensitivity analysis. The proposed model was tested on data from two separate experimental studies, and it could reproduce the observed growth characteristics in both conditions. Overall, this compartmental model with a logistic state transition rate was sufficient to explain the experimental findings and highlighted the promotive role of hypoxia in MSC proliferation. This in silico study suggests that hypoxia can enhance MSC long-term expansion mainly by delaying replicative senescence, which is indicated by the slowdown of the state transition rate in our model. Therefore, this explanatory model may provide theoretical proof for the experimentally observed MSC growth superiority under hypoxia and has the potential to further optimize MSC culture protocols for regenerative medicine applications.

The potential role of stress and sex steroids in heritable effects of sevoflurane

2021 ◽  
Author(s):  
Anatoly E Martynyuk ◽  
Ling-Sha Ju ◽  
Timothy E Morey
Keyword(s):  
Sex Steroids ◽  
Age Groups ◽  
Postnatal Period ◽  
Health Concern ◽  
General Anesthetics ◽  
Pharmacological Agents ◽  
Experimental Findings ◽  
Heritable Effects

Abstract Most surgical procedures require general anesthesia, which is a reversible deep sedation state lacking all perception. The induction of this state is possible because of complex molecular and neuronal network actions of general anesthetics (GAs) and other pharmacological agents. Laboratory and clinical studies indicate that the effects of GAs may not be completely reversible upon anesthesia withdrawal. The long-term neurocognitive effects of GAs, especially when administered at the extremes of ages, are an increasingly recognized health concern and the subject of extensive laboratory and clinical research. Initial studies in rodents suggest that the adverse effects of GAs, whose actions involve enhancement of GABA type A receptor activity (GABAergic GAs), can also extend to future unexposed offspring. Importantly, experimental findings show that GABAergic GAs may induce heritable effects when administered from the early postnatal period to at least young adulthood, covering nearly all age groups that may have children after exposure to anesthesia. More studies are needed to understand when and how the clinical use of GAs in a large and growing population of patients can result in lower resilience to diseases in the even larger population of their unexposed offspring. This minireview is focused on the authors’ published results and data in the literature supporting the notion that GABAergic GAs, in particular sevoflurane, may upregulate systemic levels of stress and sex steroids and alter expressions of genes that are essential for the functioning of these steroid systems. The authors hypothesize that stress and sex steroids are involved in the mediation of sex-specific heritable effects of sevoflurane.

scholarly journals A long-term epigenetic memory switch controls bacterial virulence bimodality

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Irine Ronin ◽  
Naama Katsowich ◽  
Ilan Rosenshine ◽  
Nathalie Q Balaban
Keyword(s):  
Mathematical Modeling ◽  
Virulence Genes ◽  
Phenotypic Variability ◽  
Bacterial Virulence ◽  
Environmental Cues ◽  
Human Pathogen ◽  
Epigenetic Memory ◽  
E Coli

When pathogens enter the host, sensing of environmental cues activates the expression of virulence genes. Opposite transition of pathogens from activating to non-activating conditions is poorly understood. Interestingly, variability in the expression of virulence genes upon infection enhances colonization. In order to systematically detect the role of phenotypic variability in enteropathogenic E. coli (EPEC), an important human pathogen, both in virulence activating and non-activating conditions, we employed the ScanLag methodology. The analysis revealed a bimodal growth rate. Mathematical modeling combined with experimental analysis showed that this bimodality is mediated by a hysteretic memory-switch that results in the stable co-existence of non-virulent and hyper-virulent subpopulations, even after many generations of growth in non-activating conditions. We identified the per operon as the key component of the hysteretic switch. This unique hysteretic memory switch may result in persistent infection and enhanced host-to-host spreading.

scholarly journals Vision of the role of long-term social stress in the formation of "diseases of civilization". mechanisms of adaptation to stressor situations and factors of its failure

2021 ◽  
Vol 11 (10) ◽  
pp. 325-331
Author(s):  
O. Hancheva ◽  
K. Romanova
Keyword(s):  
Social Stress ◽  
Experimental Studies ◽  
Human Diseases ◽  
Stress Reactions ◽  
Sources Of Information ◽  
Negative Effects ◽  
Scientific Publications ◽  
The Impact

Today, the issue of studying the mechanisms of the impact of social stress on public health and its role in the formation of key human diseases is relevant and necessary. A large number of works, both clinical observations and experimental studies, are devoted to this problem. However, despite the high interest in this problem, there are still "white spots". Therefore, the purpose of our study was to analyze modern sources of information that highlight current issues of long-term social stress and its role in the formation of "diseases of civilization." Matherials and methods: analysis of scientific publications from the following databases: Google Scholar, Web of Science, Pub Med, by keywords: rats, social stress, diseases of civilization, neuroendocrine regulation, hypothalamus, supraoptic nucleus, paravetricular nucleus. Conclusions: Thus, the analysis of resources shows the undoubted role of stress in the formation of human diseases. Many articles are devoted to the description and analysis of the negative effects of environmental factors and peculiarities of living conditions on human health. Most researchers agree on the key role of the hypothalamus in regulating the body's stress response and the presence of morphofunctional changes associated with stress. It is important to note that scientists have paid much attention to the study of individual models of stress, namely pain, immobilization and hypoxic over the past 20 years. Unfortunately, there are few facts concerning the analysis of the influence of long-term negative social factors that do not cause stereotyped reactions, but form latent changes that are inherent in classical stress reactions.

scholarly journals Modern views on amlodipine and new S-amlodipine medications

2011 ◽  
Vol 10 (4) ◽  
pp. 117-120
Author(s):  
M. V. Leonova
Keyword(s):  
Calcium Channels ◽  
Experimental Studies ◽  
Mechanisms Of Action ◽  
No Release ◽  
Pharmacologically Active ◽  
Endothelial Nitric Oxide ◽  
Smooth Myocytes ◽  
Mean Heart Rate

The review presents the latest evidence on the calcium antagonist amlodipine, summarizing its mechanisms of action, its pleiotropic, endothelial function-related effects, and its anti-atherogenic activity. Amlodipine suppresses the proliferation of vascular smooth myocytes and extracellular matrix and improves endothelial vasodilatation, despite the absence of L-type calcium channels in these cells. This mechanism is related to an increase in endothelial nitric oxide (NO) release. The results of experimental studies on the role of S and R amlodipine isomers in its hemodynamic and pleiotropic activity are presented. While S-amlodipine is a pharmacologically active blocker of L-type calcium channels, R-amlodipine increases endothelial NO release. New medications have been developed, based on S-amlodipine. It has been shown that S-amlodipine 5 mg/d is bioequivalent to amlodipine 10 mg/d. The pharmacodynamics analysis demonstrated that S-amlodipine 5 mg/d and amlodipine 10 mg/d did not differ significantly in terms of mean levels of systolic and diastolic blood pressure, or mean heart rate. S-amlodipine was better tolerated and characterised by a lower incidence of peripheral edema than amlodipine. However, the effects of S-amlodipine on hard end-points should be investigated in the long-term prospective studies.

scholarly journals Relaxation of Chipboard Beams – Analysis of Results of Exploratory Research

2018 ◽  
Vol 28 (2) ◽  
pp. 196-203
Author(s):  
Tomasz Socha ◽  
Krzysztof Kula ◽  
Arkadiusz Denisiewicz
Keyword(s):  
Mathematical Modeling ◽  
Theoretical Analysis ◽  
Experimental Studies ◽  
Experimental Tests ◽  
Exploratory Research ◽  
Method Of Least Squares ◽  
Rheological Models ◽  
In Series ◽  
Analysis Of Results

Abstract The paper presents results of experimental tests and a theoretical analysis of the phenomenon of relaxation of chipboard beams. Three linearly viscoelastic rheological models were used for mathematical modeling of the rheology of the studied material. The constants of models were determined using experimental tests and the method of least squares. Through analyses of the obtained results it was found that the rheological behavior of the beam in the specified time is best described by a five-parameter model, consisting of standard and Kelvin-Voigt models connected in series. The final verification of the model can only be ensured by conducting long-term experimental studies using a multistage load program.

Critique of a Large-Scale Organ System Model: Guytonian Cardiovascular Model

1975 ◽  
Vol 97 (3) ◽  
pp. 259-265
Author(s):  
K. Sagawa
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Large Scale ◽  
Renal Hypertension ◽  
Experimental Studies ◽  
Oxygen Demand ◽  
Sensitivity Tests ◽  
Vascular Autoregulation

This paper reviews Guyton’s model which is large not only in the number of its components but also in the time scale that it spans. The evolution of this model is explained in three stages. Guyton started with a drastically simplified model of the entire cardiovascular system as a closed hydraulic loop. It accounted for short-term regulations of cardiac output with a special emphasis on the role of blood volume and the vascular capacity. Guyton’s research objective was then directed toward the analysis of longterm regulation of arterial pressure. Two slowly acting mechanisms were considered as particularly important: (1) the marked increase or decrease of urinary output with only slight increase or decrease in arterial pressure (the renal function curve in the Guytonian model) and (2) long-term vascular autoregulation which includes changes in the extent of vascularization as well as constriction or dilation of existing vessels to match the blood flow with the oxygen demand in tissues. This second-stage model explained the transient dynamics and steady equilibrium of renal hypertension. The current version of Guyton’s model incorporates a variety of additional endocrine and neural mechanisms which parametrically control the renal function curve. With the enormous growth, the identification (or estimation) capability of the model is bound to degrade while its use for multiple parameter sensitivity tests expands. The modeller’s group has attempted to minimize the hazards by frequent checks of model predictions with experimental studies. This interactive effort, plus their concern over these long-term regulatory mechanisms, make the Guytonian model a unique venture in modern cardiovascular physiology.

Ecological Effects of Acid Deposition Upon Peatlands: A Neglected Field in "Acid-Rain" Research

1984 ◽  
Vol 41 (8) ◽  
pp. 1256-1268 ◽  
Author(s):  
Eville Gorham ◽  
Suzanne E. Bayley ◽  
David W. Schindler
Keyword(s):  
Acid Rain ◽  
Acid Deposition ◽  
Nutrient Availability ◽  
Experimental Studies ◽  
Metal Mobilization ◽  
Mass Balances ◽  
Short Term ◽  
Hydrological Changes

Certain types of peatlands are probably highly susceptible to anthropogenic acidification, yet very little research is being done on the vulnerability of bogs and fens to acid deposition. We have documented the need for such research and for studies of the role of acidification — natural and anthropogenic — in determining nutrient availability, metal mobilization, and biogeochemical cycling by fauna and microflora. Possible effects of hydrological changes, and of drainage from acid peatlands to lakes and streams, are noted. We provide an outline of possible responses of plants and animals to acidification; these should be investigated at species, community, and ecosystem levels. Studies of peatlands as possible sources of the gaseous precursors of acid deposition are needed. Different approaches to examining the responses of peatlands to acid deposition include geographical surveys, experimental studies, short-term, long-term, and paleoecological investigations, and analysis of biogeochemical mass-balances. Finally, we emphasize the need for inclusive studies of peatlands in relation to surrounding uplands and to the streams and lakes that receive their drainage.

scholarly journals The Potential Role of Learning Capacity in Cognitive Behavior Therapy for Depression: A Systematic Review of the Evidence and Future Directions for Improving Therapeutic Learning

2019 ◽  
Vol 7 (4) ◽  
pp. 668-692 ◽  
Author(s):  
Sanne J. E. Bruijniks ◽  
Robert J. DeRubeis ◽  
Steven D. Hollon ◽  
Marcus J. H. Huibers
Keyword(s):  
Behavioral Therapy ◽  
Experimental Studies ◽  
Learning Processes ◽  
Process Change ◽  
Future Directions ◽  
Learning Capacity ◽  
Treatment Processes ◽  
Therapeutic Procedures

Insight into how cognitive behavioral therapy (CBT) works is urgently needed to improve depressive outcome. First, we discuss the role of learning in CBT for depression by reviewing evidence for learning processes involved in the development and maintenance of depression. Second, we investigate the role of learning capacity as a moderator by reviewing empirical evidence for the relation between (a) CBT procedures and learning processes, (b) learning processes and CBT treatment processes, and (c) learning processes and CBT outcome. We propose that learning capacity moderates the relation between CBT procedures and change in CBT treatment processes and explains why therapeutic procedures lead to process change and long-term success in some but not all patients. Third, we identify procedures that lead to successful therapeutic learning and describe how experimental studies help to better explain causal mechanisms of change and the role of learning capacity in CBT for depression.

scholarly journals General Anesthetic-Induced Neurotoxicity in the Immature Brain: Reevaluating the Confounding Factors in the Preclinical Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ailin Luo ◽  
Xiaole Tang ◽  
Yilin Zhao ◽  
Zhiqiang Zhou ◽  
Jing Yan ◽  
...  
Keyword(s):  
Early Life ◽  
Cell Injury ◽  
Experimental Studies ◽  
Neurodevelopmental Outcome ◽  
Clinical Findings ◽  
Preclinical Studies ◽  
General Anesthetic ◽  
Potential Factors ◽  
Experimental Findings

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.

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