cellular model
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In this paper, we study stationary patterns of bistable reaction-diffusion cellular automata, i.e., models with discrete time, space and state. We show the rich variability based on the interplay of the capacity and viability and the specific form of reaction functions. While stationary k-periodic patterns occur naturally in many situations in large (exponential) numbers, there exist extreme situations for which there are no heterogeneous patterns. Moreover, nonmonotone dependence of the number of stationary patterns on the diffusion parameter is shown to be natural in the fully discrete setting.
- Klíčová slova
- cellular automata, difference equations, discrete dynamics, patterns, reaction-diffusion,
- MeSH
- biologické modely * MeSH
- celulární automaty * MeSH
- difuze MeSH
- jazyk (prostředek komunikace) MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cellular senescence is defined as irreversible cell cycle arrest caused by various processes that render viable cells non-functional, hampering normal tissue homeostasis. It has many endogenous and exogenous inducers, and is closely connected with age, age-related pathologies, DNA damage, degenerative disorders, tumor suppression and activation, wound healing, and tissue repair. However, the literature is replete with contradictory findings concerning its triggering mechanisms, specific biomarkers, and detection protocols. This may be partly due to the wide range of cellular and in vivo animal or human models of accelerated aging that have been used to study senescence and test senolytic drugs. This review summarizes recent findings concerning senescence, presents some widely used cellular and animal senescence models, and briefly describes the best-known senolytic agents.
- Klíčová slova
- aging, cellular model, mouse model, senescence, senolytics,
- MeSH
- biologické markery MeSH
- kontrolní body buněčného cyklu MeSH
- poškození DNA MeSH
- stárnutí buněk * genetika MeSH
- stárnutí * genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
Oscillating polar entities inside the biological cells, most notably microtubules, are bound to emit electromagnetic radiation. This phenomenon is described by Fröhlich kinetic equations expressing, in terms of quantum occupancy numbers of each discrete collective oscillatory mode, the balance between incoming metabolic energy flow and losses due to linear and non-linear interactions with the thermal environs of the oscillators. Hitherto, radiation losses have not been introduced as part of the balance; it was assumed that they were proportional to the modal occupation numbers. It is demonstrated that this formulation is incorrect and the radiation losses must be taken into account in the kinetic equations explicitly. Results of a numerical study of kinetic equations, enlarged in this sense, are presented for the case of three coupled oscillators which was shown to evince the essential attributes of the Fröhlich systems. Oscillator eigenfrequencies were chosen, alternatively, to fall into the MHz and the THz frequency domains. It was found that large radiation levels destroy the main hallmark of the Fröhlich systems, the energy condensation in the lowest frequency mode. The system then functions as a convertor of metabolic energy into radiation. At more moderate radiation levels, both energy condensation and significant radiation can coexist. Possible consequences for the cell physiology are suggested.
- Klíčová slova
- Bioelectromagnetism, Fröhlich systems, cell physiology, electromagnetic radiation, energy condensation,
- MeSH
- adenosintrifosfát chemie MeSH
- biologické modely MeSH
- buněčná membrána metabolismus MeSH
- cytoskelet účinky záření MeSH
- elektromagnetické záření * MeSH
- guanosintrifosfát chemie MeSH
- kinetika MeSH
- oscilometrie MeSH
- pružnost MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosintrifosfát MeSH
- guanosintrifosfát MeSH
Fröhlich model describes emission of electromagnetic field in the interior of biological cells by oscillating polar units, now mostly identified with microtubule filaments. Central element of this theory is the system of rate equations for the quantum occupancy numbers n i of collective oscillation modes. These equations describe both linear and nonlinear properties of the system; presence of the latter can lead to condensation of the incoming energy into the lowest frequency mode - a phenomenon deemed to be of major importance for cell's biochemistry, because the excited mode can engage in chemical reactions while the major part of the system remains near the equilibrium, not exposed to energetic stress. This paper explores, using a simple model, the influence of strong static electric field created by mitochondria flanking the microtubules on nonlinear interactions and, in turn, on occupancy numbers. The computed results show that simultaneous presence of both sufficient metabolic pumping and adequately elevated static electric field is necessary for the full unfolding of the hallmark properties of the Fröhlich model. It is suggested that cancer-related mitochondrial dysfunction leading to metabolic transformation has additional adverse effect mediated by diminution of static fields which in turn reduces the nonlinear processes in the Fröhlich systems, essential for energy condensation in the fundamental mode.
Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric disorders have not yet been determined. Recent advances in genetics and stem cell biology offer new prospects for cell-based modeling of psychiatric disorders. The advent of cell reprogramming and induced pluripotent stem cells (iPSC) provides an opportunity to translate genetic findings into patient-specific in vitro models. iPSC technology is less than a decade old but holds great promise for bridging the gaps between patients, genetics and biology. Despite many obvious advantages, iPSC studies still present multiple challenges. In this expert review, we critically review the challenges for modeling of psychiatric disorders, potential solutions and how iPSC technology can be used to develop an analytical framework for the evaluation and therapeutic manipulation of fundamental disease processes.
- MeSH
- autistická porucha metabolismus MeSH
- biologické modely * MeSH
- duševní poruchy genetika metabolismus MeSH
- genomika MeSH
- indukované pluripotentní kmenové buňky metabolismus MeSH
- lidé MeSH
- přeprogramování buněk MeSH
- schizofrenie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVES: This paper presents our own rat model of the cellular brain edema, induced by water intoxication (WI). The basic principle of the model is an osmotic imbalance in the cell membrane followed by an intracellular flow of sodium and simultaneous accumulation of water leading to the subsequent increase of BBB permeability. METHODS: The usefulness of the model was tested in precisely specified conditions whose results were clearly expressed. The procedure determined both how WI induces cellular edema as well as the disturbances caused by cellular edema. RESULTS: The evidence of existing cellular edema with increased BBB permeability was proved by intracellular accumulation of intravital dye with a large molecular size; increased brain-water content was confirmed by using the dry/wet weight method and by the decrease in CT density; the elevated intracranial pressure (ICP) due to the expanding volume was determined by continuous monitoring the ICP; the structural lesions were proved by identification of the myelin disintegration; and the impaired nervous functions was demonstrated by the of open field test method. CONCLUSION: Our experimental model can help the future studies of pathophysiology of cellular brain edema and is suitable for testing neuroprotective agents.
- MeSH
- chování zvířat * MeSH
- edém mozku etiologie metabolismus patologie patofyziologie MeSH
- Evansova modř MeSH
- hematoencefalická bariéra metabolismus MeSH
- intoxikace vodou komplikace metabolismus patologie patofyziologie MeSH
- intrakraniální hypertenze etiologie metabolismus patologie patofyziologie MeSH
- krysa rodu Rattus * MeSH
- lokomoce * MeSH
- modely nemocí na zvířatech * MeSH
- mozek diagnostické zobrazování metabolismus patologie MeSH
- myelinová pochva patologie MeSH
- permeabilita MeSH
- počítačová rentgenová tomografie MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus * MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Evansova modř MeSH
Among morphological phenomena, cellular patterns in developing sensory epithelia have gained attention in recent years. Although physical models for cellular rearrangements are well-established thanks to a large bulk of experimental work, their computational implementation lacks solid mathematical background and involves experimentally unreachable parameters. Here we introduce a level set-based computational framework as a tool to rigorously investigate evolving cellular patterns, and study its mathematical and computational properties. We illustrate that a compelling feature of the method is its ability to correctly handle complex topology changes, including frequent cell intercalations. Combining this accurate numerical scheme with an established mathematical model, we show that the proposed framework features minimum possible number of parameters and is capable of reproducing a wide range of tissue morphological phenomena, such as cell sorting, engulfment or internalization. In particular, thanks to precise mathematical treatment of cellular intercalations, this method succeeds in simulating experimentally observed development of cellular mosaic patterns in sensory epithelia.
- MeSH
- algoritmy * MeSH
- biologické modely * MeSH
- epitel MeSH
- morfogeneze MeSH
- software MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated β-galactosidase activity in in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of β-amyloid and tau-protein tangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase and nuclear factor kappa B signaling attenuate β-amyloid load and prevent tau-protein tangle deposition, thereby improving cognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associated with increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α, and IL-1β secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerable neuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggesting strategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.
- Klíčová slova
- Alzheimer’s disease, Amyloid β · tau protein, Cellular senescence, Neurodegenerative diseases, Telomere shortening,
- MeSH
- Alzheimerova nemoc MeSH
- amyloidní beta-protein metabolismus MeSH
- lidé MeSH
- neurodegenerativní nemoci * MeSH
- Parkinsonova nemoc metabolismus MeSH
- sekreční fenotyp asociovaný se senescencí MeSH
- signální transdukce MeSH
- stárnutí buněk * účinky léků MeSH
- zkracování telomer účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- amyloidní beta-protein MeSH
The stilbenoids, a group of naturally occurring phenolic compounds, are found in a variety of plants, including some berries that are used as food or for medicinal purposes. They are known to be beneficial for human health as anti-inflammatory, chemopreventive, and antioxidative agents. We have investigated a group of 19 stilbenoid substances in vitro using a cellular model of THP-1 macrophage-like cells and pyocyanin-induced oxidative stress to evaluate their antioxidant or pro-oxidant properties. Then we have determined any effects that they might have on the expression of the enzymes catalase, glutathione peroxidase, and heme oxygenase-1, and their effects on the activation of Nrf2. The experimental results showed that these stilbenoids could affect the formation of reactive oxygen species in a cellular model, producing either an antioxidative or pro-oxidative effect, depending on the structure pinostilbene (2) worked as a pro-oxidant and also decreased expression of catalase in the cell culture. Piceatannol (4) had shown reactive oxygen species (ROS) scavenging activity, whereas isorhapontigenin (18) had a mild direct antioxidant effect and activated Nrf2-antioxidant response element (ARE) system and elevated expression of Nrf2 and catalase. Their effects shown on cells in vitro warrant their further study in vivo.
- Klíčová slova
- Nrf2, antioxidant, macrophages, pro-oxidant, pyocyanin, stilbenoid,
- MeSH
- antioxidační responzivní elementy účinky léků MeSH
- antioxidancia chemie farmakologie MeSH
- buňky Hep G2 MeSH
- faktor 2 související s NF-E2 genetika MeSH
- lidé MeSH
- peroxidace lipidů účinky léků MeSH
- pyokyanin chemie MeSH
- stilbeny chemie farmakologie MeSH
- thiobarbituráty chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- faktor 2 související s NF-E2 MeSH
- NFE2L2 protein, human MeSH Prohlížeč
- pyokyanin MeSH
- stilbeny MeSH
- thiobarbituráty MeSH
- thiobarbituric acid MeSH Prohlížeč
Hyperglycaemia-induced oxidative stress appears to be involved in the aetiology of diabetic retinopathy (DR), a major public health issue, via altering DNA methylation process. We investigated the effect of hyperglycaemia on retinal DNA methyltransferase (DNMT) expression in diabetic mice, using Gene Expression Omnibus datasets. We also evaluated the effect of curcumin both on high glucose-induced reactive oxygen species (ROS) production and altered DNMT functions, in a cellular model of DR. We observed that three months of hyperglycaemia, in insulin-deficient Ins2 Akita mice, decrease DNMT1 and DNMT3a expression levels. In retinal pigment epithelium (RPE) cells, we also demonstrated that high glucose-induced ROS production precedes upregulation of DNMT expression and activity, suggesting that changes in DNMT function could be mediated by oxidative stress via a potential dual effect. The early effect results in decreased DNMT activity, accompanied by the highest ROS production, while long-term oxidative stress increases DNMT activity and DNMT1 expression. Interestingly, treatment with 25 μM curcumin for 6 hours restores ROS production, as well as DNMT functions, altered by the exposure of RPE to acute and chronic high glucose concentration. Our study suggests that curcumin may represent an effective antioxidant compound against DR, via restoring oxidative stress and DNMT functions, though further studies are recommended.
- MeSH
- buněčné linie MeSH
- cytosin-specifické DNA-methylasy metabolismus MeSH
- diabetická retinopatie farmakoterapie metabolismus MeSH
- experimentální diabetes mellitus farmakoterapie metabolismus MeSH
- kurkumin farmakologie terapeutické užití MeSH
- lidé MeSH
- oxidační stres účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytosin-specifické DNA-methylasy MeSH
- kurkumin MeSH
- reaktivní formy kyslíku MeSH
