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1.
Am J Chin Med ; 49(8): 1965-1999, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34961416

RESUMO

Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease that even threatens the lives of some patients infected with COVID-19. PF is a multicellular pathological process, including the initial injuries of epithelial cells, recruitment of inflammatory cells, epithelial-mesenchymal transition, activation and differentiation of fibroblasts, etc. TGF-[Formula: see text]1 acts as a key effect factor that participates in these cellular processes of PF. Recently, much attention was paid to inhibiting TGF-[Formula: see text]1 mediated cell processes in the treatment of PF with Chinese herbal medicines (CHM), an important part of traditional Chinese medicine. Here, this review first summarized the effects of TGF-[Formula: see text]1 in different cellular processes of PF. Then, this review summarized the recent research on CHM (compounds, multi-components, single medicines and prescriptions) to directly and/or indirectly inhibit TGF-[Formula: see text]1 signaling (TLRs, PPARs, micrRNA, etc.) in PF. Most of the research focused on CHM natural compounds, including but not limited to alkaloids, flavonoids, phenols and terpenes. After review, the research perspectives of CHM on TGF-[Formula: see text]1 inhibition in PF were further discussed. This review hopes that revealing the inhibiting effects of CHM on TGF-[Formula: see text]1-mediated cellular processes of PF can promote CHM to be better understood and utilized, thus transforming the therapeutic activities of CHM into practice.


Assuntos
Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/antagonistas & inibidores , COVID-19/complicações , COVID-19/metabolismo , COVID-19/virologia , Humanos , Medicina Tradicional Chinesa/métodos , Fitoterapia/métodos , Fibrose Pulmonar/complicações , Fibrose Pulmonar/metabolismo , SARS-CoV-2/fisiologia , Fator de Crescimento Transformador beta1/metabolismo
2.
Nat Commun ; 12(1): 6035, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654800

RESUMO

Between 6-20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na+, K+, and Cl- through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes confer daily variation in electrical activity. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.


Assuntos
Fenômenos Fisiológicos Celulares , Ritmo Circadiano/fisiologia , Transporte de Íons/fisiologia , Osmose , Animais , Sistema Cardiovascular/patologia , Células Cultivadas , Cloretos/metabolismo , Fibroblastos , Homeostase , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Potássio/metabolismo , Proteoma , Sódio/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/genética
3.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639226

RESUMO

The plasma membrane protects the eukaryotic cell from its surroundings and is essential for cell viability; thus, it is crucial that membrane disruptions are repaired quickly to prevent immediate dyshomeostasis and cell death. Accordingly, cells have developed efficient repair mechanisms to rapidly reseal ruptures and reestablish membrane integrity. The cortical actin cytoskeleton plays an instrumental role in both plasma membrane resealing and restructuring in response to damage. Actin directly aids membrane repair or indirectly assists auxiliary repair mechanisms. Studies investigating single-cell wound repair have often focused on the recruitment and activation of specialized repair machinery, despite the undeniable need for rapid and dynamic cortical actin modulation; thus, the role of the cortical actin cytoskeleton during wound repair has received limited attention. This review aims to provide a comprehensive overview of membrane repair mechanisms directly or indirectly involving cortical actin cytoskeletal remodeling.


Assuntos
Citoesqueleto de Actina/fisiologia , Membrana Celular/fisiologia , Fenômenos Fisiológicos Celulares , Cicatrização , Animais , Humanos , Análise de Célula Única
4.
Curr Microbiol ; 78(11): 3813-3828, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34550435

RESUMO

COVID-19, a type of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 has challenged the world as global pandemic. It has marked the identification of third generation of extremely pathogenic zoonotic coronaviruses of twenty-first century posing threat to humans and mainly targeting the lower respiratory tract. In this review, we focused on not only the structure and virology of SARS-COV-2 but have discussed in detail the molecular immunopathogenesis of this novel virus highlighting its interaction with immune system and the role of compromised or dysregulated immune response towards disease severity. We attempted to correlate the crosstalk between unregulated inflammatory outcomes with disrupted host immunity which may play a potential role towards fatal acute respiratory distress syndrome that claims to be life-threatening in COVID-19. Exploration and investigation of molecular host-virus interactions will provide a better understanding on the mechanism of fatal COVID-19 infection and also enlighten the escape routes from the same.


Assuntos
COVID-19 , Pneumonia Viral , Fenômenos Fisiológicos Celulares , Humanos , Inflamação , SARS-CoV-2
5.
Cells ; 10(9)2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34572105

RESUMO

Given the role of intermediate filaments (IFs) in normal cell physiology and scores of IF-linked diseases, the importance of understanding their molecular structure is beyond doubt. Research into the IF structure was initiated more than 30 years ago, and some important advances have been made. Using crystallography and other methods, the central coiled-coil domain of the elementary dimer and also the structural basis of the soluble tetramer formation have been studied to atomic precision. However, the molecular interactions driving later stages of the filament assembly are still not fully understood. For cytoplasmic IFs, much of the currently available insight is due to chemical cross-linking experiments that date back to the 1990s. This technique has since been radically improved, and several groups have utilized it recently to obtain data on lamin filament assembly. Here, we will summarize these findings and reflect on the remaining open questions and challenges of IF structure. We argue that, in addition to X-ray crystallography, chemical cross-linking and cryoelectron microscopy are the techniques that should enable major new advances in the field in the near future.


Assuntos
Fenômenos Fisiológicos Celulares , Citoesqueleto/metabolismo , Filamentos Intermediários/química , Filamentos Intermediários/metabolismo , Animais , Citoesqueleto/química , Humanos
6.
Mol Pharmacol ; 100(5): 502-512, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34475108

RESUMO

The activity of local anesthetics (LAs) has been attributed to the inhibition of ion channels, causing anesthesia. However, there is a growing body of research showing that LAs act on a wide range of receptors and channel proteins far beyond simple analgesia. The current concept of ligand recognition may no longer explain the multitude of protein targets influenced by LAs. We hypothesize that LAs can cause anesthesia without directly binding to the receptor proteins just by changing the physical properties of the lipid bilayer surrounding these proteins and ion channels based on LAs' amphiphilicity. It is possible that LAs act in one of the following ways: They 1) dissolve raft-like membrane microdomains, 2) impede nerve impulse propagation by lowering the lipid phase transition temperature, or 3) modulate the lateral pressure profile of the lipid bilayer. This could also explain the numerous additional effects of LAs besides anesthesia. Furthermore, the concepts of membrane-mediated activity and binding to ion channels do not have to exclude each other. If we were to consider LA as the middle part of a continuum between unspecific membrane-mediated activity on one end and highly specific ligand binding on the other end, we could describe LA as the link between the unspecific action of general anesthetics and toxins with their highly specific receptor binding. This comprehensive membrane-mediated model offers a fresh perspective to clinical and pharmaceutical research and therapeutic applications of local anesthetics. SIGNIFICANCE STATEMENT: Local anesthetics, according to the World Health Organization, belong to the most important drugs available to mankind. Their rediscovery as therapeutics and not only anesthetics marks a milestone in global pain therapy. The membrane-mediated mechanism of action proposed in this review can explain their puzzling variety of target proteins and their thus far inexplicable therapeutic effects. The new concept presented here places LAs on a continuum of structures and molecular mechanisms in between small general anesthetics and the more complex molecular toxins.


Assuntos
Potenciais de Ação/fisiologia , Anestésicos Locais/metabolismo , Fenômenos Fisiológicos Celulares/fisiologia , Microdomínios da Membrana/metabolismo , Potenciais de Ação/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/química , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Humanos , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/metabolismo , Bicamadas Lipídicas/metabolismo , Microdomínios da Membrana/efeitos dos fármacos , Estrutura Secundária de Proteína
7.
Phys Rev Lett ; 127(9): 098102, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506193

RESUMO

Temperature sensing is a ubiquitous cell behavior, but the fundamental limits to the precision of temperature sensing are poorly understood. Unlike in chemical concentration sensing, the precision of temperature sensing is not limited by extrinsic fluctuations in the temperature field itself. Instead, we find that precision is limited by the intrinsic copy number, turnover, and binding kinetics of temperature-sensitive proteins. Developing a model based on the canonical TlpA protein, we find that a cell can estimate temperature to within 2%. We compare this prediction with in vivo data on temperature sensing in bacteria.


Assuntos
Proteínas de Bactérias/fisiologia , Modelos Biológicos , Fenômenos Fisiológicos Bacterianos , Proteínas de Bactérias/química , Fenômenos Fisiológicos Celulares , Termometria , Sensação Térmica/fisiologia
8.
Cancer Sci ; 112(10): 3972-3978, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34407274

RESUMO

While starvation-induced autophagy is thought to randomly degrade cellular components, under certain circumstances autophagy selectively recognizes, sequesters, and degrades specific targets via autophagosomes. This process is called selective autophagy, and it contributes to cellular homeostasis by degrading specific soluble proteins, supramolecular complexes, liquid-liquid phase-separated droplets, abnormal or excess organelles, and pathogenic invasive bacteria. This means that autophagy, like the ubiquitin-proteasome system, strictly regulates diverse cellular functions through its selectivity. In this short review, we focus on the mechanism of "selective" autophagy, which is rapidly being elucidated.


Assuntos
Autofagossomos/fisiologia , Autofagia/fisiologia , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Fenômenos Fisiológicos Celulares , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Homeostase/fisiologia , Humanos , Organelas , Fagocitose/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Ubiquitinação
9.
J Gen Virol ; 102(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424156

RESUMO

Viruses may exploit the cardiovascular system to facilitate transmission or within-host dissemination, and the symptoms of many viral diseases stem at least in part from a loss of vascular integrity. The microvascular architecture is comprised of an endothelial cell barrier ensheathed by perivascular cells (pericytes). Pericytes are antigen-presenting cells (APCs) and play crucial roles in angiogenesis and the maintenance of microvascular integrity through complex reciprocal contact-mediated and paracrine crosstalk with endothelial cells. We here review the emerging ways that viruses interact with pericytes and pay consideration to how these interactions influence microvascular function and viral pathogenesis. Major outcomes of virus-pericyte interactions include vascular leakage or haemorrhage, organ tropism facilitated by barrier disruption, including viral penetration of the blood-brain barrier and placenta, as well as inflammatory, neurological, cognitive and developmental sequelae. The underlying pathogenic mechanisms may include direct infection of pericytes, pericyte modulation by secreted viral gene products and/or the dysregulation of paracrine signalling from or to pericytes. Viruses we cover include the herpesvirus human cytomegalovirus (HCMV, Human betaherpesvirus 5), the retrovirus human immunodeficiency virus (HIV; causative agent of acquired immunodeficiency syndrome, AIDS, and HIV-associated neurocognitive disorder, HAND), the flaviviruses dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), and the coronavirus severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2; causative agent of coronavirus disease 2019, COVID-19). We touch on promising pericyte-focussed therapies for treating the diseases caused by these important human pathogens, many of which are emerging viruses or are causing new or long-standing global pandemics.


Assuntos
Fenômenos Fisiológicos Celulares , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno , Pericitos/virologia , Viroses/metabolismo , Viroses/virologia , Animais , Comunicação Celular , Vírus da Dengue/fisiologia , Gerenciamento Clínico , Células Endoteliais/virologia , Endotélio/metabolismo , Endotélio/virologia , HIV/fisiologia , Humanos , Comunicação Parácrina , SARS-CoV-2/fisiologia , Viroses/diagnóstico , Viroses/terapia , Fenômenos Fisiológicos Virais
10.
Nutrients ; 13(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34444893

RESUMO

The extract of pomegranate (Punica granatum) has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, and antineoplastic properties. Anticancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reviewed. However, less is known about punicalagin (Pug), a prevailing compound in pomegranate, seemingly responsible for its most beneficial properties. In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized and discussed. Its attenuating effect on signaling circuits promoting cancer growth and invasion is depicted. The Pug-induced redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence, and autophagy (thus compromising neoplastic progression) is delineated. Considerations presented in this review are based mainly on data obtained from in vitro cell line models and concern the influence of Pug on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types.


Assuntos
Antineoplásicos/farmacologia , Taninos Hidrolisáveis/farmacologia , Neoplasias/prevenção & controle , Extratos Vegetais/farmacologia , Romã (Fruta)/química , Transdução de Sinais/efeitos dos fármacos , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Humanos
11.
Acta Biomater ; 134: 348-356, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34332102

RESUMO

Cells within living soft biological tissues seem to promote the maintenance of a mechanical state within a defined range near a so-called set-point. This mechanobiological process is often referred to as mechanical homeostasis. During this process, cells interact with the fibers of the surrounding extracellular matrix (ECM). It remains poorly understood, however, what individual cells actually regulate during these interactions, and how these micromechanical regulations are translated to the tissue-level to lead to what we observe as biomaterial properties. Herein, we examine this question by a combination of experiments, theoretical analysis, and computational modeling. We demonstrate that on short time scales (hours) - during which deposition and degradation of ECM fibers can largely be neglected - cells appear to not regulate the stress / strain in the ECM or their own shape, but rather only the contractile forces that they exert on the surrounding ECM. STATEMENT OF SIGNIFICANCE: Cells in soft biological tissues sense and regulate the mechanical state of the extracellular matrix to ensure structural integrity and functionality. This so-called mechanical homeostasis plays an important role in the natural history of various diseases such as aneurysms in the cardiovascular system or cancer. Yet, it remains poorly understood to date which target quantity cells regulate on the mircroscale and how it translates to the macroscale. In this paper, we combine experiments, computer simulations, and theoretical analysis to compare different hypotheses about this target quantity. This allows us to identify a likely candidate for it at least on short time scales and in the simplified environment of tissue equivalents.


Assuntos
Fenômenos Fisiológicos Celulares , Homeostase , Matriz Extracelular , Humanos
12.
ACS Appl Mater Interfaces ; 13(28): 32673-32689, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34227792

RESUMO

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.


Assuntos
Materiais Biomiméticos/química , Regeneração Óssea/efeitos dos fármacos , Hidrogéis/química , Nanocompostos/química , Osteogênese/efeitos dos fármacos , Tecidos Suporte/química , Adesivos/síntese química , Adesivos/química , Adesivos/toxicidade , Alendronato/análogos & derivados , Alendronato/toxicidade , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/toxicidade , Osso e Ossos/efeitos dos fármacos , Linhagem Celular , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Dextranos/síntese química , Dextranos/química , Dextranos/toxicidade , Durapatita/síntese química , Durapatita/química , Durapatita/toxicidade , Feminino , Hidrogéis/síntese química , Hidrogéis/toxicidade , Masculino , Camundongos , Nanocompostos/toxicidade , Ácido Poliglutâmico/síntese química , Ácido Poliglutâmico/química , Ácido Poliglutâmico/toxicidade , Ratos Sprague-Dawley , Suínos , Engenharia Tecidual/métodos
14.
Elife ; 102021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34191720

RESUMO

Our understanding of cellular and structural biology has reached unprecedented levels of detail, and computer visualisation techniques can be used to create three-dimensional (3D) representations of cells and their environment that are useful in both teaching and research. However, extracting and integrating the relevant scientific data, and then presenting them in an effective way, can pose substantial computational and aesthetic challenges. Here we report how computer artists, experts in computer graphics and cell biologists have collaborated to produce a tool called Nanoscape that allows users to explore and interact with 3D representations of cells and their environment that are both scientifically accurate and visually appealing. We believe that using Nanoscape as an immersive learning application will lead to an improved understanding of the complexities of cellular scales, densities and interactions compared with traditional learning modalities.


Assuntos
Fenômenos Fisiológicos Celulares , Imageamento Tridimensional/métodos , Aprendizagem , Interface Usuário-Computador , Imageamento Tridimensional/instrumentação
15.
Elife ; 102021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34106045

RESUMO

Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy.


Assuntos
Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Colágeno/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linfócitos T/metabolismo , Microambiente Tumoral/fisiologia , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Matriz Extracelular/metabolismo , Feminino , Inibidores de Checkpoint Imunológico/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Proteína-Lisina 6-Oxidase/metabolismo
16.
J Vis Exp ; (171)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34096905

RESUMO

Clinical studies show electrical stimulation (ES) to be a potential therapy for the healing and regeneration of various tissues. Understanding the mechanisms of cell response when exposed to electrical fields can therefore guide the optimization of clinical applications. In vitro experiments aim to help uncover those, offering the advantage of wider input and output ranges that can be ethically and effectively assessed. However, the advancements in in vitro experiments are difficult to reproduce directly in clinical settings. Mainly, that is because the ES devices used in vitro differ significantly from the ones suitable for patient use, and the path from the electrodes to the targeted cells is different. Translating the in vitro results into in vivo procedures is therefore not straightforward. We emphasize that the cellular microenvironment's structure and physical properties play a determining role in the actual experimental testing conditions and suggest that measures of charge distribution can be used to bridge the gap between in vitro and in vivo. Considering this, we show how in silico finite element modelling (FEM) can be used to describe the cellular microenvironment and the changes generated by electric field (EF) exposure. We highlight how the EF couples with geometric structure to determine charge distribution. We then show the impact of time dependent inputs on charge movement. Finally, we demonstrate the relevance of our new in silico model methodology using two case studies: (i) in vitro fibrous Poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT-PSS) scaffolds and (ii) in vivo collagen in extracellular matrix (ECM).


Assuntos
Fenômenos Fisiológicos Celulares , Microambiente Celular , Estimulação Elétrica , Eletricidade , Eletrodos , Análise de Elementos Finitos , Humanos
17.
Phys Biol ; 18(4)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34156353

RESUMO

A common signature of cell adaptation to stress is the improved resistance upon priming by prior stress exposure. In the context of hyperthermia, priming or preconditioning with sublethal heat shock can be a useful tool to confer thermotolerance and competitive advantage to cells. In the present study, we develop a data-driven modeling framework that is simple and generic enough to capture a broad set of adaptation behaviors to heat stress at both molecular and cellular levels. The model recovers the main features of thermotolerance and clarifies the tradeoff principles which maximize the thermotolerance effect. It therefore provides an effective predictive tool to design preconditioning and fractionation hyperthermia protocols for therapeutic purpose.


Assuntos
Fenômenos Fisiológicos Celulares , Resposta ao Choque Térmico/fisiologia , Modelos Biológicos , Termotolerância/fisiologia
18.
PLoS Comput Biol ; 17(6): e1009069, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34166365

RESUMO

Despite the unprecedented growth in our understanding of cell biology, it still remains challenging to connect it to experimental data obtained with cells and tissues' physiopathological status under precise circumstances. This knowledge gap often results in difficulties in designing validation experiments, which are usually labor-intensive, expensive to perform, and hard to interpret. Here we propose PHENSIM, a computational tool using a systems biology approach to simulate how cell phenotypes are affected by the activation/inhibition of one or multiple biomolecules, and it does so by exploiting signaling pathways. Our tool's applications include predicting the outcome of drug administration, knockdown experiments, gene transduction, and exposure to exosomal cargo. Importantly, PHENSIM enables the user to make inferences on well-defined cell lines and includes pathway maps from three different model organisms. To assess our approach's reliability, we built a benchmark from transcriptomics data gathered from NCBI GEO and performed four case studies on known biological experiments. Our results show high prediction accuracy, thus highlighting the capabilities of this methodology. PHENSIM standalone Java application is available at https://github.com/alaimos/phensim, along with all data and source codes for benchmarking. A web-based user interface is accessible at https://phensim.tech/.


Assuntos
Algoritmos , Fenômenos Fisiológicos Celulares , Fenótipo , Software , Antineoplásicos/farmacologia , Benchmarking , Biologia Celular , Linhagem Celular , Linhagem Celular Tumoral , Biologia Computacional , Simulação por Computador , Feminino , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , MAP Quinase Quinase Quinases/genética , Metformina/farmacologia , Proteínas Proto-Oncogênicas/genética , Transdução de Sinais/efeitos dos fármacos , Mutações Sintéticas Letais , Biologia de Sistemas , Fator de Necrose Tumoral alfa/genética
19.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067696

RESUMO

Nanomaterials are proven to affect the biological activity of mammalian and microbial cells profoundly. Despite this fact, only surface chemistry, charge, and area are often linked to these phenomena. Moreover, most attention in this field is directed exclusively at nanomaterial cytotoxicity. At the same time, there is a large body of studies showing the influence of nanomaterials on cellular metabolism, proliferation, differentiation, reprogramming, gene transfer, and many other processes. Furthermore, it has been revealed that in all these cases, the shape of the nanomaterial plays a crucial role. In this paper, the mechanisms of nanomaterials shape control, approaches toward its synthesis, and the influence of nanomaterial shape on various biological activities of mammalian and microbial cells, such as proliferation, differentiation, and metabolism, as well as the prospects of this emerging field, are reviewed.


Assuntos
Células/efeitos dos fármacos , Nanoestruturas/química , Tamanho da Partícula , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Fenômenos Físicos
20.
Cells ; 10(6)2021 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071113

RESUMO

From time immemorial, humans have exploited plants as a source of food and medicines. The World Health Organization (WHO) has recorded 21,000 plants with medicinal value out of 300,000 species available worldwide. The promising modern "multi-omics" platforms and tools have been proven as functional platforms able to endow us with comprehensive knowledge of the proteome, genome, transcriptome, and metabolome of medicinal plant systems so as to reveal the novel connected genetic (gene) pathways, proteins, regulator sequences and secondary metabolite (molecule) biosynthetic pathways of various drug and protein molecules from a variety of plants with therapeutic significance. This review paper endeavors to abridge the contemporary advancements in research areas of multi-omics and the information involved in decoding its prospective relevance to the utilization of plants with medicinal value in the present global scenario. The crosstalk of medicinal plants with genomics, transcriptomics, proteomics, and metabolomics approaches will be discussed.


Assuntos
Fenômenos Fisiológicos Celulares/fisiologia , Metaboloma/fisiologia , Plantas Medicinais/metabolismo , Transcriptoma/fisiologia , Humanos , Metabolômica/métodos , Proteoma/metabolismo , Proteômica/métodos
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