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2.
Adv Exp Med Biol ; 1232: 77-83, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893397

RESUMO

Instantaneous orthostatic hypotension (INOH) is one of the main types of orthostatic dysregulation in children and adolescents. In patients with INOH arterial pressure drops considerably after active standing and is slow to recover. We investigated changes in cerebral oxygenation in the bilateral prefrontal cortex during an active standing test in juvenile INOH patients to evaluate changes in cerebral oxygen metabolism. We enrolled 82 INOH patients (mean age 13.8 ± 2.2 years, 52 mild and 30 severe patients) at Nihon University Itabashi Hospital from October 2013 to April 2018. We measured cerebral oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin levels in the bilateral prefrontal cortex using near-infrared spectroscopy during an active standing test. In severe INOH patients, cerebral oxygenation of the right prefrontal cortex remained constant when blood pressure dropped; however, de-oxy-Hb significantly increased. These findings confirm that there is asymmetrical autoregulation between the right and left prefrontal cortex.


Assuntos
Circulação Cerebrovascular , Hipotensão Ortostática , Adolescente , Circulação Cerebrovascular/fisiologia , Criança , Homeostase , Humanos , Hipotensão Ortostática/fisiopatologia , Oxiemoglobinas , Espectroscopia de Luz Próxima ao Infravermelho
3.
Chemosphere ; 239: 124758, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31514009

RESUMO

Trace elements such as copper (Cu) and arsenic (As) are two of the major contaminants and well-known inducers of cognitive deficits and neurobehavioral changes. This study evaluated the immunotoxicity of their individual or combined exposure on different brain regions in chickens. Consequently, nuclear damage and organelle lesions, especially mitochondria were observed under Cu or/and As stress, in which positive regulation of key proteins, dynamin-related protein 1 (Drp1), Cytochrome C (Cyt c), BCL2-associated X (Bax), Caspases 3 and P53 was detected by qRCR and Western blot analyses, indicating disturbed mitochondrial dynamic equilibrium and apoptosis execution. In addition, qRCR analysis confirmed the involvement of cytokines secreted by different populations of helper T cells, indicative of cellular immunity. Gene expression studies showed marked up regulation of Th1/Th17 cytokines along with heat shock protein (HSP) 70, a synergism was noted in co-administration group. Interesting, lower apoptosis index was noted in brainstem compared to cerebrum and cerebellum. An intense immunosuppression and heat shock response against Cu or/and As was also seen in cerebrum and cerebellum but not in brainstem. In conclusion, our study suggests a synergistic neurotoxicity in chickens under Cu and As exposure. These findings provide a basic understanding of mitochondrial abnormality-initiated neuropathology in response to environmental pollutant mixtures, suggesting an adaptive response to the frangibility of the central nerve system.


Assuntos
Arsenitos/toxicidade , Encéfalo/efeitos dos fármacos , Galinhas/imunologia , Cobre/toxicidade , Tolerância Imunológica/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Poluentes Ambientais/toxicidade , Resposta ao Choque Térmico/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Masculino , Dinâmica Mitocondrial/efeitos dos fármacos
5.
Adv Exp Med Biol ; 1209: 23-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728863

RESUMO

The highly conserved catabolic process of autophagy delivers unwanted proteins or damaged organelles to vacuoles for degradation and recycling. This is essential for the regulation of cellular homeostasis, stress adaptation, and programmed cell death in eukaryotes. In particular, emerging evidence indicates that autophagy plays a multifunctional regulatory role in plant innate immunity during plant-pathogen interactions. In this review, we highlight existing knowledge regarding the involvement of autophagy in plant immunity, mechanisms functioning in the induction of autophagy upon pathogen infection, and possible directions for future research.


Assuntos
Autofagia , Imunidade Vegetal , Homeostase , Imunidade Vegetal/imunologia , Vacúolos
6.
Adv Exp Med Biol ; 1209: 181-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728871

RESUMO

Autophagy, a highly conserved and multistep lysosomal degradation process, plays a pivotal role in maintaining cellular and physiological homeostasis. Of note, autophagy controls intracellular homeostasis and cell responses to stresses by regulating the self-renewal, maturation, and survival of immune cells. And dysregulation of autophagy in immune cells may contribute to the inflammatory disorders and defect in immune responses against invasive pathogens. Accumulating evidence have indicated that dysregulated autophagy participates in the pathology of immune-related diseases. Therefore, targeting autophagy might represent a promising therapeutic strategy for treatment of immune-related diseases. In this chapter, we focus on discussing the link between autophagy and pathogenesis of immune-related diseases, as well as the dysregulation of autophagy-related signaling pathways, in different diseases. Moreover, we highlight the therapeutic potential of currently used small-molecule modulators of autophagy for treatment of immune-related diseases and illustrate the mechanisms of these small-molecule modulators.


Assuntos
Autofagia , Doenças do Sistema Imunitário , Fatores Imunológicos , Homeostase , Humanos , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/fisiopatologia , Fatores Imunológicos/química , Fatores Imunológicos/uso terapêutico , Transdução de Sinais
7.
Adv Exp Med Biol ; 1197: 69-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732935

RESUMO

Candida albicans is an opportunistic pathogen colonizing the oropharyngeal, esophageal, and gastrointestinal mucosa in most healthy humans. In immunocompromised hosts, this fungal organism can cause mucosal candidiasis in these sites. C. albicans also causes fungemia, a serious consequence of cancer cytotoxic chemotherapy, which is thought to develop from fungal translocation through compromised mucosal barriers. Changes in endogenous bacterial population size or composition as well as changes in the host environment can transform fungal commensals into opportunistic pathogens in the upper and lower GI tract. Pioneering studies from our group have shown that a ubiquitous oral commensal of the mitis streptococcal group (Streptococcus oralis) has a mutualistic relationship with C. albicans, with C. albicans enabling streptococcal biofilm growth at mucosal sites, and S. oralis facilitating invasion of the oral and esophageal mucosa by C. albicans. In these studies, we used a cortisone-induced immunosuppression mouse model. More recently, the development of a novel mouse chemotherapy model has allowed us to examine the interactions of C. albicans with the endogenous bacterial microbiota in the oral and small intestinal mucosa, two sites adversely affected by cytotoxic chemotherapy. In this model, oral inoculation with C. albicans causes severe dysbiosis in the mucosal bacterial composition in both sites. We also found that antibiotic treatment ameliorates invasion of the oral mucosa but aggravates dissemination through the intestinal mucosa. In this chapter, we discuss work from our laboratory and others examining the relationships of C. albicans with oral bacteria and their role in mucosal homeostasis or disease.


Assuntos
Candida albicans , Microbiota , Mucosa Bucal , Animais , Candida albicans/fisiologia , Candidíase/microbiologia , Modelos Animais de Doenças , Homeostase , Humanos , Camundongos , Microbiota/fisiologia , Mucosa Bucal/microbiologia , Streptococcus oralis
8.
Adv Exp Med Biol ; 1189: 179-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31758535

RESUMO

Foxp3-expressing regulatory T cells (Tregs) perform a vital function in the maintenance of immune homeostasis. A large part of Treg suppressive function is derived from their ability to control and restrict the availability of co-signal molecules to other T cells. However, Tregs themselves also depend on many of the same co-signals for their own homeostasis, making this a complex system of feedback. In this chapter, we discuss the critical role of co-signaling in Treg cell biology.


Assuntos
Transdução de Sinais , Linfócitos T Reguladores/citologia , Fatores de Transcrição Forkhead/metabolismo , Homeostase , Humanos
9.
Life Sci ; 237: 116913, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622609

RESUMO

AIMS: To explore the impact of GC administration periconceptionally on the glucose metabolism of adult offspring (male and female) and whether this periconception exposure might influence the metabolic outcomes when the offspring are also treated with dexamethasone in adult life. MATERIALS AND METHODS: Rats received a daily injection of dexamethasone (1 mg/kg, body mass) or saline solution (1 mL/kg body mass) for 7 consecutive days prior became pregnant. Male and female offspring had glucose homeostasis assessed at 3- and 6-month-old and after dexamethasone treatment (1 mg/kg, body mass) or vehicle for 5 consecutive days. Then, murinometric, functional, biochemical, and histomorphometric analyses were performed. KEY FINDINGS: Male and female offspring born from rats treated with GC prior to becoming pregnant had none of the murinometric and metabolic outcomes (i.e., body mass, food intake, blood glucose, plasma triacylglycerol, and glucose tolerance) changed up to 6-month-old. None of the expected diabetogenic effects caused by dexamethasone treatment at 6-month of age (i.e., elevation in fasting blood glucose, plasma insulin, triacylglycerol, and albumin, glucose intolerance, insulin insensitivity, augmentation in hepatic glycogen content, and increase in pancreatic islet mass) was observed in offspring born from rats treated with dexamethasone in the prepregnancy period. However, periconceptional exposure to GC predisposed the offspring of both sexes to a higher prevalence of augmented fed blood glucose values. SIGNIFICANCE: These results give validity for the use of GC as anti-inflammatory purposes in this critical periconceptional period, but highlight the importance to consider all parental habits when interpreting adult outcomes.


Assuntos
Dexametasona/administração & dosagem , Intolerância à Glucose/tratamento farmacológico , Homeostase , Secreção de Insulina/efeitos dos fármacos , Cuidado Pré-Concepcional , Animais , Glicemia/análise , Peso Corporal , Feminino , Glucocorticoides/administração & dosagem , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/crescimento & desenvolvimento , Masculino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Prenhez , Ratos , Ratos Wistar
11.
Adv Exp Med Biol ; 1175: 1-13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583582

RESUMO

Neuroglia represent a diverse population of non-neuronal cells in the nervous systems, be that peripheral, central, enteric or autonomic nervous system. Arguably, these cells represent about half of the volume of the human brain. This volumetric ratio, and by extension glia to neurone ratio, not only widely differ depending on the size of the animal species brain and its positioning on the phylogenetic tree, but also vary between the regions of an individual brain. Neuroglia derived from a dual origin (ectoderm and mesodermal) and in an assorted morphology, yet their functional traits can be mainly classified into being keepers of homeostasis (water, ions, neurotransmitters, metabolites, fuels, etc.) and defenders (e.g., against microbial organisms, etc.) of the nervous system. As these capabilities go awry, neuroglia ultimately define their fundamental role in most, if not, all neuropathologies. This concept presented in this chapter serves as a general introduction into the world of neuroglia and subsequent topics covered by this book.


Assuntos
Neuroglia/fisiologia , Animais , Homeostase , Humanos , Neurônios , Neurotransmissores , Filogenia
12.
Adv Exp Med Biol ; 1175: 45-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583584

RESUMO

Astrocytes are principal cells responsible for maintaining the brain homeostasis. Additionally, these glial cells are also involved in homocellular (astrocyte-astrocyte) and heterocellular (astrocyte-other cell types) signalling and metabolism. These astroglial functions require an expression of the assortment of molecules, be that transporters or pumps, to maintain ion concentration gradients across the plasmalemma and the membrane of the endoplasmic reticulum. Astrocytes sense and balance their neurochemical environment via variety of transmitter receptors and transporters. As they are electrically non-excitable, astrocytes display intracellular calcium and sodium fluctuations, which are not only used for operative signalling but can also affect metabolism. In this chapter we discuss the molecules that achieve ionic gradients and underlie astrocyte signalling.


Assuntos
Astrócitos/fisiologia , Encéfalo/fisiologia , Transdução de Sinais , Cálcio , Homeostase , Humanos , Bombas de Íon/fisiologia , Neuroglia , Receptores de Neurotransmissores/fisiologia , Sódio
13.
Adv Exp Med Biol ; 1175: 129-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583587

RESUMO

Microglia constitute the major immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other glial cells. These resident immune cells are critical for proper brain development, actively maintain brain health throughout the lifespan and rapidly adapt their function to the physiological or pathophysiological needs of the organism. Cutting-edge fate mapping and imaging techniques applied to animal models enabled a revolution in our understanding of their roles during normal physiological conditions. Here, we highlight studies that demonstrate the embryonic yolk sac origin of microglia and describe factors, including crosstalk with the periphery and external environment, that regulate their differentiation, homeostasis and function in the context of healthy CNS. The diversity of microglial phenotypes observed across the lifespan, between brain compartments and between sexes is also discussed. Understanding what defines specific microglial phenotypes is critical for the development of innovative therapies to modulate their effector functions and improve clinical outcomes.


Assuntos
Sistema Nervoso Central/citologia , Microglia/fisiologia , Animais , Encéfalo , Homeostase , Humanos , Saco Vitelino/citologia
15.
Mol Biol (Mosk) ; 53(5): 790-798, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31661478

RESUMO

Recently, much attention has been drawn to unraveling the mechanisms of neurodegenerative and neuroinflammatory disease pathogenesis. A special role in the development of neuropathologies is assigned to the interaction of the nervous and the immune systems. Microglia are the cells of the immune system that function as resident macrophages of the central nervous system (CNS) and are involved in the development of CNS, as well as in homeostatic interactions. Impaired microglia can contribute to neuroinflammation and neurodegeneration. With the help of genome editing technologies, the main paradigms in the development and functions of microglia have been addressed. At the same time, an understanding of the mechanisms of regulation of microglia in normal and pathological conditions is necessary to create an effective therapy aimed at treating various neurological diseases. This review focuses on recent findings on the origin of microglia, its regulatory role in the central nervous system, as well as its contribution to the development of neuroinflammation.


Assuntos
Sistema Nervoso Central/citologia , Sistema Nervoso Central/fisiologia , Homeostase , Inflamação/patologia , Microglia/fisiologia , Doenças Neurodegenerativas/patologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Humanos , Inflamação/fisiopatologia , Microglia/citologia , Microglia/patologia , Doenças Neurodegenerativas/fisiopatologia
16.
Rev Prat ; 69(5): 537-545, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-31626464

RESUMO

Sleep is a physiological condition essential to life, present in all living organisms with a neuronal and glial network. Its functions, not fully understood, include the conservation of energy, the regulation of our immune system and brain function through the modulation of synaptic plasticity and the elimination of substances accumulated during wakefulness. Sleep in human is characterized by two exclusive states, the non-REM and the REM -paradoxical- sleep, whose occurrence is driven by a cyclic organi zation. Sleep and wakefulness result from complex mechanisms involving a hetero geneous transition of different brain structures from one physiological state to another. The sleep duration and distribution of sleep over 24 hours are regulated by complex interconnected mechanisms, involving both the need for sleep accumulated during wakefulness -homeostatic process- and biological rhythm -mainly the circadian process- under the influence of external synchronizers like light-dark cycle. The propensity to sleep at a given moment is regulated by a physiological signal, sleepiness, in connection with the level of vigilance. The characteristics of sleep are relatively stable for a given individual because of a strong genetic determinism, but varies in duration and architecture according to age, individual habits, sleep schedules and environmental constraints. An understanding of the physiology of sleep is important for the clinician, allowing a better understanding of sleep dysfunction, responsible for various and frequent sleep disorders equiring appropriate care.


Assuntos
Transtornos do Sono-Vigília , Sono , Ritmo Circadiano/fisiologia , Homeostase , Humanos , Sono/fisiologia , Sono REM/fisiologia , Vigília/fisiologia
17.
Postepy Biochem ; 65(3): 163-172, 2019 09 30.
Artigo em Polonês | MEDLINE | ID: mdl-31643163

RESUMO

The intestinal microflora plays a key role in maintaining homeostasis in the human body. Microbes affect, among others, energy conversion and absorption of nutrients, regulate immune system and help to protect the host organism from pathogenic microorganisms. The balanced composition of the intestinal microflora can be easily disturbed and any changes caused by diet, stress, obesity, diseases of the digestive system or medication may lead to pro-inflammatory immune responses and initiation of disease processes, including cancer. Maintaining intestinal microflora homeostasis is therefore extremely important for human health. In order to restore it, it is most often used to take specimens with appropriate bacterial cultures, i. e. probiotics. Due to the fact that yoghurts are a source of probiotic bacteria, their regular consumption may be a strong point in the prevention of various types of diseases, including civilization diseases and cancer. This article reviews the literature in the area of using yogurt bacteria in the prevention of cancer. Issues addressed in the article relate to the characteristics of yogurt bacteria, beneficial effects of probiotics on human health, anti-cancer properties of yogurt bacteria and their metabolites, i. e. immunoregulation, prevention of bacterial infections, maintenance of cellular connections in the intestine and anti-cancer activity of bacterial metabolites.


Assuntos
Bactérias , Neoplasias/dietoterapia , Neoplasias/prevenção & controle , Probióticos , Iogurte/microbiologia , Bactérias/metabolismo , Homeostase , Humanos , Neoplasias/microbiologia , Probióticos/metabolismo
18.
Nature ; 574(7779): 575-580, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645732

RESUMO

The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases1,2. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.


Assuntos
Epigênese Genética , Glicólise/genética , Histonas/química , Histonas/metabolismo , Ácido Láctico/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Lisina/química , Lisina/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Transcrição Genética
19.
Sheng Li Xue Bao ; 71(5): 769-782, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646331

RESUMO

Autoimmune diseases are a kind of chronic diseases with unclear etiology, which has the characteristics of repetition and difficulty to cure completely. Aerobic exercise, as an effective intervention method for chronic diseases, has also received extensive attention in the field of the prevention and treatment of autoimmune diseases. In this paper, the effects of aerobic exercise on immune system and autoimmune diseases in recent years are reviewed, and the related mechanisms are discussed. It is pointed out that aerobic exercise can improve the homeostasis of immune environment by affecting the number and function of immune cells, inhibit the systemic inflammatory response of the body, and then delay the occurrence and development of autoimmune diseases.


Assuntos
Doenças Autoimunes/prevenção & controle , Exercício , Sistema Imunitário , Homeostase , Humanos
20.
Nat Chem Biol ; 15(10): 1001-1008, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31548693

RESUMO

Glycolysis plays a central role in producing ATP and biomass. Its control principles, however, remain incompletely understood. Here, we develop a method that combines 2H and 13C tracers to determine glycolytic thermodynamics. Using this method, we show that, in conditions and organisms with relatively slow fluxes, multiple steps in glycolysis are near to equilibrium, reflecting spare enzyme capacity. In Escherichia coli, nitrogen or phosphorus upshift rapidly increases the thermodynamic driving force, deploying the spare enzyme capacity to increase flux. Similarly, respiration inhibition in mammalian cells rapidly increases both glycolytic flux and the thermodynamic driving force. The thermodynamic shift allows flux to increase with only small metabolite concentration changes. Finally, we find that the cellulose-degrading anaerobe Clostridium cellulolyticum exhibits slow, near-equilibrium glycolysis due to the use of pyrophosphate rather than ATP for fructose-bisphosphate production, resulting in enhanced per-glucose ATP yield. Thus, near-equilibrium steps of glycolysis promote both rapid flux adaptation and energy efficiency.


Assuntos
Metabolismo Energético/fisiologia , Glicólise , Animais , Linhagem Celular , Clostridium acetobutylicum , Clostridium cellulolyticum , Escherichia coli/classificação , Escherichia coli/metabolismo , Glucose/metabolismo , Homeostase , Camundongos , Nitrogênio , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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