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1.
FASEB J ; 35(9): e21798, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339064

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID-19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR-ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium-binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID-19, pathological similarities of the affected lungs between COVID-19 and S100A8-induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll-like receptor 4/Myeloid differentiation protein-2 (TLR4/MD-2) and mediates hyper-inflammation even after elimination of endotoxin-producing extrinsic pathogens, analogous findings between COVID-19-associated ARDS and pre-metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID-19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID-19-associated ARDS.


Assuntos
COVID-19/complicações , Calgranulina A/fisiologia , Síndrome da Liberação de Citocina/etiologia , Inflamação/etiologia , Pandemias , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/fisiologia , Animais , Antivirais/farmacologia , COVID-19/genética , COVID-19/patologia , Calgranulina A/sangue , Calgranulina A/genética , Quimiocina CXCL11/sangue , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/patologia , Dissacarídeos/farmacologia , Dissacarídeos/uso terapêutico , Modelos Animais de Doenças , Descoberta de Drogas , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Humanos , Inflamação/genética , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Antígeno 96 de Linfócito/fisiologia , Macaca mulatta , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Mutação , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/metabolismo , Especificidade da Espécie , Fosfatos Açúcares/farmacologia , Fosfatos Açúcares/uso terapêutico , Receptor 4 Toll-Like/fisiologia , Regulação para Cima , Internalização do Vírus
2.
Nutrients ; 13(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445014

RESUMO

The maternal diet can potentially influence the life-course health of the child. A poor-quality maternal diet creates nutrient deficiencies and affects immune-metabolic regulation during pregnancy. The nutrient-based overall dietary quality can be assessed using the Nutrient-Rich Food Index 9.3 (NRF9.3), which measures adherence to the national reference daily values of nutrient intake. Pro- and anti-inflammatory nutrient intake can be assessed using the energy-adjusted dietary inflammatory index (E-DII), a comprehensive index of diet-derived inflammatory capacity. Using these indices, we assessed the overall dietary quality and inflammatory potential of pregnant women during mid-gestation in an urban area of Japan (n = 108) and found that there was a strong inverse correlation between the NRF9.3 and E-DII scores. Comparison of the scores among the tertiles of NRF9.3 or E-DII indicated that dietary fiber, vitamin C, vitamin A, and magnesium mainly contributed to the variability of both indices. Intake of vegetables and fruits was positively associated with high NRF9.3 scores and negatively associated with high E-DII scores, after adjustment for maternal age, pre-pregnancy body mass index, and educational level. Consistent with the previous studies that used dietary pattern analysis, this study also demonstrated that vegetables and fruits were the food groups chiefly associated with high dietary quality and low inflammatory potential among pregnant Japanese women.


Assuntos
Dieta Saudável , Inflamação/prevenção & controle , Fenômenos Fisiológicos da Nutrição Materna , Avaliação Nutricional , Estado Nutricional , Valor Nutritivo , Recomendações Nutricionais , Adulto , Registros de Dieta , Dieta Saudável/efeitos adversos , Ingestão de Energia , Feminino , Frutas , Humanos , Inflamação/etiologia , Inflamação/fisiopatologia , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Tóquio , Verduras
3.
Biol Aujourdhui ; 215(1-2): 63-72, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34397376

RESUMO

Obesity is considered a pandemic responsible for millions of deaths worldwide for many years. At the end of 2019, the Coronavirus disease 2019 (COVID-19) appeared, causing the death of more than a million people in less than a year. Numerous studies suggest that obesity could be defined as key to the onset of severe forms of this emerging disease. Indeed, SARS-CoV2 infects the host by binding to ACE2 receptors present on the surface of the cells and causes excessive secretion of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α, which lead to developing acute respiratory distress syndrome (ARDS). It therefore seems essential to make up effective preventive strategies to protect this part of the population from the risk of developing a severe form of COVID-19. The ketogenic diet, which is low in sugars and high in fat, has interesting properties, both in the fight against obesity but also against severe infections. This article focuses on the latest scientific advances that make it possible to consider the ketogenic diet as a preventive strategy that simultaneously reduces the development of obesity while strengthening the immune system, two key actions in the fight against SARS-CoV2 infections and severe forms of COVID-19.


Assuntos
COVID-19/prevenção & controle , Dieta Cetogênica , Inflamação/etiologia , Obesidade/prevenção & controle , Pandemias , SARS-CoV-2 , Adipócitos/metabolismo , Animais , COVID-19/complicações , COVID-19/imunologia , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina/etiologia , Dieta Cetogênica/efeitos adversos , Suscetibilidade a Doenças , Humanos , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Leptina/fisiologia , Obesidade/complicações , Obesidade/dietoterapia , Obesidade/epidemiologia , Síndrome do Desconforto Respiratório/etiologia
4.
Nutrients ; 13(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34444955

RESUMO

Diet and dietary components have profound effects on the composition of the gut microbiota and are among the most important contributors to the alteration in bacterial flora. This review examines the effects the "Western", "plant-based", "high-fat", "medical ketogenic", and "Mediterranean" diets have on the composition of the gut microbiota in both mice and human subjects. We show that specific dietary components that are commonly found in the "plant-based" and "Mediterranean" diet play a role in shifting the microbial composition. This review further evaluates the bacterial metabolites that are associated with diet, and their role in systemic inflammation and metabolic endotoxemia. Furthermore, the associations between diet/dietary components and altering bacterial composition, may lead to potential therapeutic targets for type II diabetes, obesity, and inflammatory diseases.


Assuntos
Dieta/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Fenômenos Fisiológicos da Nutrição , Animais , Dieta/métodos , Dieta Hiperlipídica/efeitos adversos , Dieta Cetogênica/efeitos adversos , Dieta Mediterrânea/efeitos adversos , Dieta Vegetariana/efeitos adversos , Dieta Ocidental/efeitos adversos , Endotoxemia/etiologia , Endotoxemia/microbiologia , Humanos , Inflamação/etiologia , Inflamação/microbiologia , Camundongos
5.
Front Immunol ; 12: 642373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413846

RESUMO

Bacterial products are able to act on nociceptive neurons during pathogenic infection. Neurogenic inflammation is an active part of pain signaling and has recently been shown to impact host-pathogen defense. Bacillus anthracis Edema Toxin (ET) produces striking edema in peripheral tissues, but the cellular mechanisms involved in tissue swelling are not completely understood. Here, we find that nociceptive neurons play a role in ET-induced edema and inflammation in mice. Subcutaneous footpad infection of B. anthracis Sterne caused ET-dependent local mechanical allodynia, paw swelling and body weight gain. Subcutaneous administration of ET induced paw swelling and vascular leakage, the early phases of which were attenuated in the absence of Trpv1+ or Nav1.8+ nociceptive neurons. Nociceptive neurons express the anthrax toxin receptor ANTXR2, but this did not mediate ET-induced edema. ET induced local cytokine expression and neutrophil recruitment, which were dependent in part on Trpv1+ nociceptive neurons. Ablation of Trpv1+ or Nav1.8+ nociceptive neurons also attenuated early increases in paw swelling and body weight gain during live B. anthracis infection. Our findings indicate that nociceptive neurons play an active role in inflammation caused by B. anthracis and Edema Toxin to potentially influence bacterial pathogenesis.


Assuntos
Antraz/complicações , Antígenos de Bactérias/toxicidade , Toxinas Bacterianas/toxicidade , Inflamação/etiologia , Nociceptores/metabolismo , Animais , Antraz/fisiopatologia , Bacillus anthracis , Camundongos , Camundongos Endogâmicos C57BL , Nociceptores/efeitos dos fármacos
6.
Oxid Med Cell Longev ; 2021: 8671713, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457119

RESUMO

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.


Assuntos
COVID-19/complicações , Síndrome da Liberação de Citocina/patologia , Endotélio Vascular/patologia , Inflamação/patologia , Estresse Oxidativo , SARS-CoV-2/isolamento & purificação , Doenças Vasculares/patologia , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Endotélio Vascular/virologia , Humanos , Inflamação/etiologia , Inflamação/terapia , Doenças Vasculares/etiologia , Doenças Vasculares/terapia
7.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360840

RESUMO

Obesity is characterized as a chronic, low-grade inflammation state accompanied by the infiltration of immune cells into adipose tissue and higher levels of inflammatory cytokines and chemokines. This study aimed to investigate the mechanisms and effects of Coptidis Rhizoma (CR) on obesity and its associated inflammation. First, we applied a network pharmacology strategy to search the target genes and pathways regulated by CR in obesity. Next, we performed in vivo experiments to confirm the antiobesity and anti-inflammatory effects of CR. Mice were assigned to five groups: normal chow (NC), control (high-fat diet (HFD)), HFD + CR 200 mg/kg, HFD + CR 400 mg/kg, and HFD + metformin 200 mg/kg. After 16 weeks of the experimental period, CR administration significantly reduced the weight of the body, epididymal fat, and liver; it also decreased insulin resistance, as well as the area under the curve of glucose in the oral glucose tolerance test and triglyceride in the oral fat tolerance test. We observed a decrease in adipose tissue macrophages (ATMs) and inflammatory M1 ATMs, as well as an increase in anti-inflammatory M2 ATMs. Gene expression levels of inflammatory cytokines and chemokines, including tumor necrosis factor-α, F4/80, and C-C motif chemokine (CCL)-2, CCL4, and CCL5, were suppressed in adipose tissue in the CR groups than levels in the control group. Additionally, histological analyses suggested decreased fat accumulation in the epididymal fat pad and liver in the CR groups than that in the control group. Taken together, these results suggest that CR has a therapeutic effect on obesity-induced inflammation, and it functions through the inhibition of macrophage-mediated inflammation in adipose tissue.


Assuntos
Citocinas/genética , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/metabolismo , Obesidade/complicações , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Simulação por Computador , Dieta Hiperlipídica , Regulação da Expressão Gênica , Inflamação/etiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Sci Rep ; 11(1): 16290, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381066

RESUMO

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about » of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Transtornos Plaquetários/etiologia , COVID-19/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Plaquetas/ultraestrutura , COVID-19/tratamento farmacológico , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Trombocitopenia/etiologia , Resultado do Tratamento , Adulto Jovem
9.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445644

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is considered a manifestation of metabolic syndrome (MS) and is characterized by the accumulation of triglycerides and a varying degree of hepatic injury, inflammation, and repair. Moreover, peroxisome-proliferator-activated receptors (PPARs) play a critical role in the pathophysiological processes in the liver. There is extensive evidence of the beneficial effect of polyphenols such as resveratrol (RSV) and quercetin (QRC) on the treatment of liver pathology; however, the mechanisms underlying their beneficial effects have not been fully elucidated. In this work, we show that the mechanisms underlying the beneficial effects of RSV and QRC against inflammation in liver damage in our MS model are due to the activation of novel pathways which have not been previously described such as the downregulation of the expression of toll-like receptor 4 (TLR4), neutrophil elastase (NE) and purinergic receptor P2Y2. This downregulation leads to a decrease in apoptosis and hepatic fibrosis with no changes in hepatocyte proliferation. In addition, PPAR alpha and gamma expression were altered in MS but their expression was not affected by the treatment with the natural compounds. The improvement of liver damage by the administration of polyphenols was reflected in the normalization of serum transaminase activities.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Síndrome Metabólica/complicações , Quercetina/farmacologia , Receptores Purinérgicos/metabolismo , Resveratrol/farmacologia , Animais , Antioxidantes/farmacologia , Citocinas/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Wistar , Receptores Purinérgicos/genética
10.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445566

RESUMO

BACKGROUND: The communication between the brain and the immune system is a cornerstone in animal physiology. This interaction is mediated by immune factors acting in both health and pathogenesis, but it is unclear how these systems molecularly and mechanistically communicate under changing environmental conditions. Behavioural fever is a well-conserved immune response that promotes dramatic changes in gene expression patterns during ectotherms' thermoregulatory adaptation, including those orchestrating inflammation. However, the molecular regulators activating the inflammatory reflex in ectotherms remain unidentified. METHODS: We revisited behavioural fever by providing groups of fish a thermal gradient environment during infection. Our novel experimental setup created temperature ranges in which fish freely moved between different thermal gradients: (1) wide thermoregulatory range; T° = 6.4 °C; and (2) restricted thermoregulatory range; T° = 1.4 °C. The fish behaviour was investigated during 5-days post-viral infection. Blood, spleen, and brain samples were collected to determine plasmatic pro- and anti-inflammatory cytokine levels. To characterize genes' functioning during behavioural fever, we performed a transcriptomic profiling of the fish spleen. We also measured the activity of neurotransmitters such as norepinephrine and acetylcholine in brain and peripheral tissues. RESULTS: We describe the first set of the neural components that control inflammatory modulation during behavioural fever. We identified a neuro-immune crosstalk as a potential mechanism promoting the fine regulation of inflammation. The development of behavioural fever upon viral infection triggers a robust inflammatory response in vivo, establishing an activation threshold after infection in several organs, including the brain. Thus, temperature shifts strongly impact on neural tissue, specifically on the inflammatory reflex network activation. At the molecular level, behavioural fever causes a significant increase in cholinergic neurotransmitters and their receptors' activity and key anti-inflammatory factors such as cytokine Il10 and Tgfß in target tissues. CONCLUSION: These results reveal a cholinergic neuronal-based mechanism underlying anti-inflammatory responses under induced fever. We performed the first molecular characterization of the behavioural fever response and inflammatory reflex activation in mobile ectotherms, identifying the role of key regulators of these processes. These findings provide genetic entry points for functional studies of the neural-immune adaptation to infection and its protective relevance in ectotherm organisms.


Assuntos
Comportamento Animal , Infecções por Birnaviridae/complicações , Febre/patologia , Imunidade , Vírus da Necrose Pancreática Infecciosa/fisiologia , Inflamação/patologia , Reflexo , Animais , Infecções por Birnaviridae/virologia , Regulação da Temperatura Corporal , Citocinas/metabolismo , Febre/etiologia , Peixes , Inflamação/etiologia
11.
Biomolecules ; 11(7)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34356687

RESUMO

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel-Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly increased compared with that in the controls. Our case report suggests an involvement of adventitial artery microcirculation by inflammation in the course of COVID-19. Without evident signs of current infection by SARS-CoV-2, endothelial cells show a spectrum of structural and functional alterations that can fuel the cardiovascular complications observed in people infected with SARS-CoV-2.


Assuntos
Arteriopatias Oclusivas/etiologia , COVID-19/complicações , Inflamação/etiologia , Idoso , Arteriopatias Oclusivas/patologia , COVID-19/patologia , Feminino , Humanos , Inflamação/patologia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/patologia , MicroRNAs/análise , Microcirculação , SARS-CoV-2/isolamento & purificação
12.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360595

RESUMO

After myocardial infarction (MI), a strong inflammatory response takes place in the heart to remove the dead tissue resulting from ischemic injury. A growing body of evidence suggests that timely resolution of this inflammatory process may aid in the prevention of adverse cardiac remodeling and heart failure post-MI. The present challenge is to find a way to stimulate this process without interfering with the reparative role of the immune system. Extracellular vesicles (EVs) are natural membrane particles that are released by cells and carry different macromolecules, including proteins and non-coding RNAs. In recent years, EVs derived from various stem and progenitor cells have been demonstrated to possess regenerative properties. They can provide cardioprotection via several mechanisms of action, including immunomodulation. In this review, we summarize the role of the innate immune system in post-MI healing. We then discuss the mechanisms by which EVs modulate cardiac inflammation in preclinical models of myocardial injury through regulation of monocyte influx and macrophage function. Finally, we provide suggestions for further optimization of EV-based therapy to improve its potential for the treatment of MI.


Assuntos
Cardiotônicos/administração & dosagem , Vesículas Extracelulares/transplante , Inflamação/terapia , Infarto do Miocárdio/complicações , Células-Tronco/citologia , Animais , Humanos , Inflamação/etiologia , Inflamação/patologia
13.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360618

RESUMO

Activation of the Ca2+ activated Cl- channel TMEM16A is proposed as a treatment in inflammatory airway disease. It is assumed that activation of TMEM16A will induce electrolyte secretion, and thus reduce airway mucus plugging and improve mucociliary clearance. A benefit of activation of TMEM16A was shown in vitro and in studies in sheep, but others reported an increase in mucus production and airway contraction by activation of TMEM16A. We analyzed expression of TMEM16A in healthy and inflamed human and mouse airways and examined the consequences of activation or inhibition of TMEM16A in asthmatic mice. TMEM16A was found to be upregulated in the lungs of patients with asthma or cystic fibrosis, as well as in the airways of asthmatic mice. Activation or potentiation of TMEM16A by the compounds Eact or brevenal, respectively, induced acute mucus release from airway goblet cells and induced bronchoconstriction in mice in vivo. In contrast, niclosamide, an inhibitor of TMEM16A, blocked mucus production and mucus secretion in vivo and in vitro. Treatment of airway epithelial cells with niclosamide strongly inhibited expression of the essential transcription factor of Th2-dependent inflammation and goblet cell differentiation, SAM pointed domain-containing ETS-like factor (SPDEF). Activation of TMEM16A in people with inflammatory airway diseases is likely to induce mucus secretion along with airway constriction. In contrast, inhibitors of TMEM16A may suppress pulmonary Th2 inflammation, goblet cell metaplasia, mucus production, and bronchoconstriction, partially by inhibiting expression of SPDEF.


Assuntos
Anoctamina-1/metabolismo , Asma/patologia , Constrição Patológica/complicações , Fibrose Cística/patologia , Inflamação/patologia , Muco/metabolismo , Mucosa Respiratória/patologia , Animais , Anoctamina-1/genética , Asma/etiologia , Asma/metabolismo , Fibrose Cística/etiologia , Fibrose Cística/metabolismo , Células HEK293 , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Camundongos , Mucosa Respiratória/metabolismo
14.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360655

RESUMO

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.


Assuntos
Antioxidantes/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo , Ozônio/administração & dosagem , Animais , Artrite Experimental/etiologia , Artrite Experimental/patologia , Artrite Reumatoide/etiologia , Artrite Reumatoide/patologia , Catalase/metabolismo , Citocinas/metabolismo , Glutationa/metabolismo , Humanos , Inflamação/etiologia , Inflamação/patologia , Oxidantes Fotoquímicos/administração & dosagem , Oxirredução , Ratos
15.
Rev Med Virol ; 31(4): e2199, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260778

RESUMO

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Patients can be asymptomatic or present respiratory and gastrointestinal symptoms, and even multiple-organ failure which can lead to death. The balance between an effective antiviral response and dysregulated immune response is the key factor determining the severity of COVID-19 progression. A systematic review was performed using the NCBI-PubMed database to find the articles related to COVID-19 immunity and inflammatory response published from 1 December 2019 to 15 April 2020. Haematological, immunological and biochemical parameters were extracted and correlated with disease severity, age and presence of comorbidities. Twelve articles were analysed comprising a total of 1042 hospitalized patients infected with SARS-CoV-2 and 95 different parameters. Total lymphocyte count and levels of CD3+ and CD4+ T cells were decreased in severe and critical cases. Neutrophilia was found in patients who progressed to acute respiratory distress syndrome (ARDS). Interleukin-six (IL-6) was high in mild and severe patients regardless of comorbidities. Erythrocyte sedimentation rate (ESR) and count and C-reactive protein (CRP) levels were increased regardless of disease severity or presence of comorbidities. High levels of D-dimer and lactate dehydrogenase were present in diabetic patients and patients who developed ARDS. Procalcitonin levels were elevated to varying degrees in severe and critical patients. We conclude that the total lymphocyte count, CD3+ and CD4+ T cells are low, especially in severe and critical COVID-19 patients; ESR, CRP and IL-6 were elevated, independent of the severity of disease. Understanding the inflammatory response of COVID-19 patients is essential for the development of better therapeutic and management strategies.


Assuntos
COVID-19/imunologia , Imunidade/imunologia , Inflamação/imunologia , Biomarcadores/sangue , COVID-19/sangue , COVID-19/complicações , Humanos , Inflamação/etiologia
16.
Am J Cardiol ; 155: 128-134, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34315570

RESUMO

Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p < 0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p < 0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p < 0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, p = 0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, p = 0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, p = 0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, p = 0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, p = 0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.


Assuntos
Biomarcadores/sangue , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/sangue , Enteropatias Perdedoras de Proteínas/sangue , Doenças Vasculares/sangue , Resistência Vascular/fisiologia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Cardiopatias Congênitas/sangue , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Enteropatias Perdedoras de Proteínas/etiologia , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia , Adulto Jovem
17.
Clin Immunol ; 229: 108798, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34280578

RESUMO

Inflammatory response in patients with COPD secondary to organic dust exposure (OD-COPD) is poorly understood. We therefore aimed to characterize inflammatory and immune profile from peripheral blood mononuclear cells (PBMC) in a group of patients with mild-to-moderate COPD secondary to organic dust exposure (OD-COPD), tobacco smoking (T-COPD), or both. We compared T, B and NK cells distribution and inflammatory (TNF-α, Il-1ß, IL-6), type 1 (IFN-γ), type 2 (IL-4, IL-13) and type 3 (IL-17) immunity related cytokines at baseline, and after stimulation with LPS, flagellin and CD3/CD28 beads in all COPD groups. OD-COPD displayed significantly lower NK cells and CD8+ T cells compared with controls. After flagellin stimulation, T-COPD had significantly lower IL-13 levels than OD-COPD and controls (p < 0.05) whereas IFN-γ tended to be lower in OD-COPD. All COPD groups displayed higher IL-1ß and IL-17 than controls after CD3/CD28 stimulation. Inflammatory responses in OD-COPD were different from T-COPD. OD-COPD displayed higher levels of type 2 immunity related cytokines.


Assuntos
Poeira/imunologia , Compostos Orgânicos/toxicidade , Doença Pulmonar Obstrutiva Crônica/imunologia , Idoso , Agricultura , Linfócitos B/imunologia , Linfócitos B/patologia , Estudos de Casos e Controles , Citocinas/biossíntese , Feminino , Humanos , Inflamação/etiologia , Inflamação/imunologia , Inflamação/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Fumar Tabaco/efeitos adversos
18.
PLoS One ; 16(7): e0254167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214123

RESUMO

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , Dexametasona/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Inflamação/prevenção & controle , SARS-CoV-2 , Viremia/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Biomarcadores , COVID-19/sangue , COVID-19/diagnóstico por imagem , Dexametasona/farmacologia , Endotélio Vascular/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Lesão Pulmonar/sangue , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Masculino , Oxigênio/sangue , Projetos Piloto , Carga Viral , Viremia/sangue
19.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299105

RESUMO

The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Disbiose/complicações , Microbioma Gastrointestinal , Sistema Imunitário/imunologia , Inflamação/patologia , Animais , Humanos , Inflamação/etiologia
20.
Int J Mol Sci ; 22(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299150

RESUMO

Cera Flava (CF), a natural extract obtained from beehives, is widely used in dermatological products owing to its wound healing, wrinkle reduction, UV-protective, and skin cell turnover stimulation effects. However, its effect on AD-like skin lesions is unknown. In this study, we used a mouse model of AD to evaluate the effects of CP at the molecular and phenotypic levels. Topical house dust mite (HDM) sensitization and challenge were performed on the dorsal skin of NC/Nga mice to induce AD-like cutaneous lesions, phenotypes, and immunologic responses. The topical application of CF for 6 weeks relieved HDM-induced AD-like phenotypes, as quantified by the dermatitis severity score, scratching frequency, and skin moisture. CP decreased immunoglobulin E, histamine, and thymic stromal lymphopoietin levels. Histopathological analysis showed that CF decreased epidermal thickening and the number of mast cells. CF attenuated HDM-induced changes in the expression of skin barrier-related proteins. Furthermore, CF decreased the mRNA levels of inflammatory factors, including interleukin (IL)-1ß, IL-4, IL-13, IL-8, TARC, MDC, and RANTES, in dorsal skin tissue via the TLR2/MyD88/TRAF6/ERK pathway. CF influences skin barrier function and immune regulation to alleviate AD symptoms. It may therefore be an effective alternative to topical steroids for the treatment of AD.


Assuntos
Dermatite Atópica/tratamento farmacológico , Inflamação/prevenção & controle , Pele/efeitos dos fármacos , Ceras/farmacologia , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Histamina/metabolismo , Imunoglobulina E/metabolismo , Fatores Imunológicos/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Pyroglyphidae , Pele/imunologia , Pele/metabolismo , Pele/patologia
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