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1.
Life Sci ; 264: 118617, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33096114

RESUMO

BACKGROUND: COVID-19-associated acute respiratory distress syndrome (ARDS) is associated with significant morbidity and high levels of mortality. This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS. MAIN BODY: The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis. The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of neutrophil extracellular traps (NETs) producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID-19 are discussed in detail.


Assuntos
/imunologia , /complicações , /patogenicidade , Trombose/complicações , Trombose/fisiopatologia , Células Epiteliais Alveolares/fisiologia , Plaquetas/fisiologia , /tratamento farmacológico , Citocinas/fisiologia , Células Endoteliais/fisiologia , Humanos , Macrófagos Alveolares/fisiologia , Neutrófilos/fisiologia , /patologia , Trombose/imunologia
3.
J Biol Regul Homeost Agents ; 34(5): 1689-1697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33107270

RESUMO

Increased intestinal permeability due to barrier dysfunction is supposed to cause several gastrointestinal diseases. We have previously demonstrated that a single ß-carotene (BC) dose protects against increase in anaphylactic response in ß-lactoglobulin (BLG)-sensitized mice with no effect on the epithelial permeability and weak recovery of villi length. Utilizing the same murine ex vivo intestinal model, the aim of this study was to investigate the effect of different BC doses on BLG-mediated intestinal epithelial barrier disturbances. Jejunum was harvested from BLG-sensitized mice pretreated with either one of three different doses of BC (5, 10 and 20 mg/ kg body weight) and mounted on Ussing Chambers. Transepithelial electrical resistance (TER) and short-circuit current (Isc) were recorded as indicators of intestinal epithelial barrier function. Histopathological analysis of the intestine was carried out for the control and experimental mice. TNF-α and IL-6 levels were determined in serum using ELISA, and the analysis of antioxidant activity was performed for reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). BC was capable of enhancing the intestinal barrier function, as indicated by the increased TER and the decreased Isc. Intestinal damage characterized by the shortening of villi and infiltration of intestinal lymphocytes was significantly reversed by BC pretreatment. Such effects of BC were accompanied by a reduction in the levels of IL-6 and TBARS and an increase of GSH. TNF-α levels were reduced only at the lowest BC dose. These findings may encourage the use of BC-based therapies for controlling the breakdown of the intestinal barrier in vivo.


Assuntos
Antioxidantes/fisiologia , Citocinas/fisiologia , Mucosa Intestinal/fisiopatologia , beta Caroteno/uso terapêutico , Animais , Glutationa , Lactoglobulinas , Camundongos , Permeabilidade , Substâncias Reativas com Ácido Tiobarbitúrico
4.
BMJ Case Rep ; 13(9)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933914

RESUMO

We present a case of a 50-year-old man with COVID-19 infection and acute respiratory distress syndrome as a result of a cytokine storm and use of anakinra, an interleukin 1-receptor antagonist that is normally used in the treatment of autoinflammatory disorders in adult patients. We saw a reduction in oxygen requirement and improvements in inflammatory markers and ferritin. Although we cannot determine its clinical efficacy from one case study, it may have a positive effect on the proinflammatory state that is associated with cytokine storm in COVID-19 infection.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/fisiologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Índice de Gravidade de Doença
6.
Hum Cell ; 33(4): 954-962, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32813218

RESUMO

Interferon-stimulated gene 15 (ISG15) is a critical ubiquitin-like protein that can be conjugated to proteins via the ISGylation system to modify them posttranslationally. Furthermore, ISG15 can be detected as non-conjugated or free, intracellularly and/or extracellularly. Both conjugated and free ISG15 participate in different cancer types, including breast cancer. Here, we highlighted the findings on ISG15 and protein ISGylation, and their implications in the field of breast cancer research. ISG15 emerges as a central element in mammary tumors and may become a crucial protein in the strategies for detection, prognosis, and therapy of breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Citocinas/genética , Ubiquitinas/genética , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Citocinas/metabolismo , Citocinas/fisiologia , Feminino , Humanos , Terapia de Alvo Molecular , Ubiquitinas/metabolismo , Ubiquitinas/fisiologia
7.
Mol Neurobiol ; 57(12): 4921-4928, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32813238

RESUMO

The global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore and examine the possible links between COVID-19 and ischemic stroke (IS). Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. The swift increase in the knowledge of SARS-CoV-2 has given creditable evidence that SARS-CoV-2 infected patients also encounter neurological deficits. As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra. The COVID-19 pandemic has affected people with various pre-existing diseases, including IS, in such a way that these patients need special care and attention for their survival. Several clinical trials are currently ongoing worldwide as well as many other projects are in different stages of conceptualization and planning to facilitate the effective management of stroke patients with COVID-19 infection.


Assuntos
Betacoronavirus , Isquemia Encefálica/etiologia , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Acidente Vascular Cerebral/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Barreira Hematoencefálica , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Quimiotaxia de Leucócito , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Encefalite Viral/complicações , Encefalite Viral/fisiopatologia , Hemodinâmica , Humanos , Inflamação , Modelos Imunológicos , Modelos Neurológicos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Receptores Virais/fisiologia , Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia
8.
Med Hypotheses ; 143: 110125, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763657

RESUMO

The novel coronavirus (SARS-CoV-2) is primarily a respiratory pathogen and its clinical manifestations are dominated by respiratory symptoms, the most severe of which is acute respiratory distress syndrome (ARDS). However, COVID-19 is increasingly recognized to cause an overwhelming inflammatory response and cytokine storm leading to end organ damage. End organ damage to heart is one of the most severe complications of COVID-19 that increases the risk of death. We proposed a two-fold mechanism responsible for causing acute coronary events in patients with COVID-19 infection: Cytokine storm leading to rapid onset formation of new coronary plaques along with destabilization of pre-existing plaques and direct myocardial injury secondary to acute systemic viral infection. A well-coordinated immune response is the first line innate immunity against a viral infection. However, an uncoordinated response and hypersecretion of cytokines and chemokines lead to immune related damage to the human body. Human Coronavirus (HCoV) infection causes infiltration of inflammatory cells that cause excessive production of cytokines, proteases, coagulation factors, oxygen radicals and vasoactive molecules causing endothelial damage, disruption of fibrous cap and initiation of formation of thrombus. Systemic viral infections also cause vasoconstriction leading to narrowing of vascular lumen and stimulation of platelet activation via shear stress. The resultant cytokine storm causes secretion of hypercoagulable tissue factor without consequential increase in counter-regulatory pathways such as AT-III, activated protein C and plasminogen activator type 1. Lastly, influx of CD4+ T-cells in cardiac vasculature results in an increased production of cytokines that stimulate smooth muscle cells to migrate into the intima and generate collagen and other fibrous products leading to advancement of fatty streaks to advanced atherosclerotic lesions. Direct myocardial damage and cytokine storm leading to destabilization of pre-existing plaques and accelerated formation of new plaques are the two instigating mechanisms for acute coronary syndromes in COVID-19.


Assuntos
Síndrome Coronariana Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Modelos Cardiovasculares , Pandemias , Pneumonia Viral/complicações , Síndrome Coronariana Aguda/fisiopatologia , Linfócitos T CD4-Positivos/imunologia , Quimiocinas/fisiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Humanos , Imunidade Inata , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/fisiopatologia , Ativação Plaquetária , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Vasoconstrição , Viroses/complicações , Viroses/imunologia
9.
Endocr Res ; 45(3): 210-215, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32628899

RESUMO

BACKGROUND: Uptake of coronaviruses by target cells involves binding of the virus by cell ectoenzymes. For the etiologic agent of COVID-19 (SARS-CoV-2), a receptor has been identified as angiotensin-converting enzyme-2 (ACE2). Recently it has been suggested that plasma membrane integrins may be involved in the internalization and replication of clinically important coronaviruses. For example, integrin αvß3 is involved in the cell uptake of a model porcine enteric α-coronavirus that causes human epidemics. ACE2 modulates the intracellular signaling generated by integrins. OBJECTIVE: We propose that the cellular internalization of αvß3 applies to uptake of coronaviruses bound to the integrin, and we evaluate the possibility that clinical host T4 may contribute to target cell uptake of coronavirus and to the consequence of cell uptake of the virus. DISCUSSION AND CONCLUSIONS: The viral binding domain of the integrin is near the Arg-Gly-Asp (RGD) peptide-binding site and RGD molecules can affect virus binding. In this same locale on integrin αvß3 is the receptor for thyroid hormone analogues, particularly, L-thyroxine (T4). By binding to the integrin, T4 has been shown to modulate the affinity of the integrin for other proteins, to control internalization of αvß3 and to regulate the expression of a panel of cytokine genes, some of which are components of the 'cytokine storm' of viral infections. If T4 does influence coronavirus uptake by target cells, other thyroid hormone analogues, such as deaminated T4 and deaminated 3,5,3'-triiodo-L-thyronine (T3), are candidate agents to block the virus-relevant actions of T4 at integrin αvß3 and possibly restrict virus uptake.


Assuntos
Infecções por Coronavirus/virologia , Integrina alfaVbeta3/metabolismo , Vírus da Diarreia Epidêmica Suína/metabolismo , Receptores Virais/efeitos dos fármacos , Hormônios Tireóideos/farmacologia , Animais , Betacoronavirus/metabolismo , Sítios de Ligação , Citocinas/fisiologia , Células Epiteliais/virologia , Humanos , Oligopeptídeos/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Receptores Virais/química , Receptores Virais/metabolismo , Suínos , Hormônios Tireóideos/fisiologia , Tiroxina/fisiologia , Internalização do Vírus
10.
Surg Clin North Am ; 100(4): 681-693, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32681869

RESUMO

Chronic wounds present a unique therapeutic challenge to heal. Chronic wounds are colonized with bacteria and the presence of a biofilm that further inhibits the normal wound healing processes, and are locked into a very damaging proinflammatory response. The treatment of chronic wounds requires a coordinated approach, including debridement of devitalized tissue, minimizing bacteria and biofilm, control of inflammation, and the use of specialized dressings to address the specific aspects of the particular nonhealing ulcer.


Assuntos
Angiopatias Diabéticas/fisiopatologia , Úlcera Cutânea/fisiopatologia , Cicatrização/fisiologia , Anti-Infecciosos/uso terapêutico , Biofilmes/efeitos dos fármacos , Doença Crônica , Citocinas/fisiologia , Angiopatias Diabéticas/imunologia , Angiopatias Diabéticas/terapia , Farmacorresistência Bacteriana/fisiologia , Quimioterapia Combinada , Humanos , Imunidade Celular/fisiologia , Peptídeo Hidrolases/fisiologia , Úlcera Cutânea/imunologia , Úlcera Cutânea/terapia , Cicatrização/imunologia , Infecção dos Ferimentos/imunologia , Infecção dos Ferimentos/fisiopatologia , Infecção dos Ferimentos/terapia
11.
J Toxicol Sci ; 45(6): 327-337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32493875

RESUMO

Hydrolyzed wheat proteins (HWPs) contained in cosmetics have occasionally caused immediate-type hypersensitivity following repeated skin exposure. Although the Cosmetic Ingredient Review Expert Panel concluded that < 3,500 Da HWP is safe for use in cosmetics, it remains biologically unknown how allergenic HWPs evoke immediate-type allergy percutaneously. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) induces type 2 immune responses, which play an essential role in the pathogenesis of immediate-type allergy. Previously, we demonstrated that protein allergens in cultured human keratinocytes strongly induced long-form TSLP (loTSLP) transcription. However loTSLP-regulating signaling by HWP is poorly understood. In this study, we performed global gene expression analysis by microarray to investigate how the allergenic HWP acts on epidermal keratinocytes and the induction of loTSLP. Compared to human serum albumin (HSA), allergenic HWP induced a distinct gene expression pattern and preferentially activated various inflammatory pathways (High Mobility Group Box 1, Interleukin [IL]-6, IL-8, and acute phase response signaling). We identified 85 genes as potential nuclear factor-kappa B (NF-κB) target genes in GP19S-treated cells, compared with 29 such genes in HSA-treated cells. In addition, HWP specifically altered IL-17 signaling pathways in which transcription factors, NF-κB and activator protein-1, were activated. NF-κB signaling may be an important factor for HWP-induced inflammatory loTSLP transcription via inhibition assay. In conclusion, allergenic HWP caused an easily sensitizable milieu of activated inflammatory pathways and induced NF-κB-dependent loTSLP transcription in keratinocytes.


Assuntos
Citocinas , Queratinócitos/imunologia , NF-kappa B/metabolismo , Proteínas de Plantas/efeitos adversos , Transdução de Sinais , Transcrição Genética , Células Cultivadas , Citocinas/genética , Citocinas/fisiologia , Expressão Gênica , Humanos , Hidrólise , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/genética , Inflamação/etiologia , Inflamação/genética , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Triticum
12.
J Biol Regul Homeost Agents ; 34(3): 767-773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32476380

RESUMO

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.


Assuntos
Infecções por Coronavirus/complicações , Citocinas/fisiologia , Síndrome de Linfonodos Mucocutâneos/virologia , Pneumonia Viral/complicações , Betacoronavirus , Criança , Citocinas/antagonistas & inibidores , Humanos , Interleucina-1 , Interleucinas , Pandemias
13.
J R Coll Physicians Edinb ; 50(2): 133-137, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32568282

RESUMO

Broadly speaking, pharmacological treatments for COVID-19 can be divided into those acting on upstream pathways early on in the disease process via suppression of viral replication or by inhibiting cell entry, and those acting on downstream pathways later on via selective attenuation of the adaptive immune cytokine-mediated inflammatory response. The antiviral drug remdesivir has been shown to shorten duration of disease while interferon beta-1b may speed up viral clearance. The results with hydroxychloroquine have thus far been rather disappointing. Trials with selective cytokine blockers including anti-interleukin-1 (anti-IL-1) and anti-interleukin-6 (anti-IL-6), have shown some promise in more severe cases, with further confirmation being required from large-scale phase-3 randomised controlled trials. The likelihood is that combination therapy addressing both upstream and downstream pathways may be required to prevent progression of severe COVID-19 infection in susceptible older patients with comorbidities and we believe further studies are now warranted to specifically target such at-risk groups who are more prone to worse outcomes.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/complicações , Citocinas/fisiologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Pandemias , Pneumonia Viral/complicações
15.
Neurologia ; 35(4): 245-251, 2020 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: covidwho-178369

RESUMO

INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/etiologia , Citocinas/fisiologia , Transtornos Mentais/etiologia , Doenças Neurodegenerativas/etiologia , Pandemias , Pneumonia Viral/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/fisiopatologia , Síndrome da Liberação de Citocina/psicologia , Progressão da Doença , Humanos , Sistema Imunitário/fisiopatologia , Sistema Imunitário/virologia , Inflamação , Mediadores da Inflamação/fisiologia , Transtornos Mentais/epidemiologia , Modelos Imunológicos , Modelos Neurológicos , Doenças Neurodegenerativas/epidemiologia , Neuroimunomodulação/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Saúde Pública , Fatores de Tempo
16.
Neurologia ; 35(4): 245-251, 2020 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: covidwho-71976

RESUMO

INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/etiologia , Citocinas/fisiologia , Transtornos Mentais/etiologia , Doenças Neurodegenerativas/etiologia , Pandemias , Pneumonia Viral/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/fisiopatologia , Síndrome da Liberação de Citocina/psicologia , Progressão da Doença , Humanos , Sistema Imunitário/fisiopatologia , Sistema Imunitário/virologia , Inflamação , Mediadores da Inflamação/fisiologia , Transtornos Mentais/epidemiologia , Modelos Imunológicos , Modelos Neurológicos , Doenças Neurodegenerativas/epidemiologia , Neuroimunomodulação/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Saúde Pública , Fatores de Tempo
17.
Braz Oral Res ; 34: e038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374812

RESUMO

The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.


Assuntos
Fator Ativador de Células B/análise , Diabetes Mellitus Tipo 2/complicações , Periodontite/imunologia , Periodontite/patologia , Adulto , Idoso , Biomarcadores/análise , Biópsia , Estudos de Casos e Controles , Citocinas/análise , Citocinas/fisiologia , Diabetes Mellitus Tipo 2/imunologia , Feminino , Expressão Gênica , Gengiva/imunologia , Gengiva/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese/imunologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/análise
18.
Neumol. pediátr. (En línea) ; 15(2): 301-307, mayo 2020. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1099514

RESUMO

The recent outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been brought to global attention in the search of knowledge about the virus and its pathogenesis. The immune response is essential to control and eliminate the infection, however, maladjusted immune responses may result in severe disease fisiopathology. Gaining a deeper understanding of the interaction between SARS-CoV-2 and the immune systems of the hosts may help us anticipate the development of persistent pulmonary inflammation and, why not, be the first step to therapeutic success and trying to save more lives. In this review, we provide an update on CoV virology and our vision of pathogenesis understanding it from the stages of infection, without forgetting the cytokine storm resulting from the interaction of the virus with ACE2 receptors widely distributed in the body.


La reciente emergencia de síndrome de distrés respiratorio agudo producido por coronavirus 2 (SARS-CoV-2), enfermedad denominada COVID-19 ha traído la atención mundial a la búsqueda de conocimiento sobre este virus y su patogenia. La respuesta inmune es esencial para controlar y erradicar la infección, sin embargo, las respuestas inmunes descontroladas pueden resultar en la fisiopatología de la enfermedad grave. Lograr una comprensión más profunda de la interacción entre SARS-COV-2 y el sistema inmune de los huéspedes podría ayudar a anticiparnos al desarrollo de una inflamación pulmonar persistente causada por el SARS-CoV-2, y por qué no, ser la puerta de entrada al éxito terapéutico e intentar salvar mayor número de vidas. En esta revisión, proporcionamos una actualización sobre la virología y nuestra visión de la patogenia, entendiéndola desde las fases o etapas de la infección, sin olvidar el estallido de citoquinas resultantes de la interacción del virus con los receptores ACE2 ampliamente distribuidos en el organismo.


Assuntos
Humanos , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Betacoronavirus/fisiologia , Citocinas/fisiologia , Peptidil Dipeptidase A/fisiologia , Betacoronavirus/patogenicidade , Imunidade Inata/fisiologia
19.
Eur J Immunol ; 50(8): 1195-1208, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32365223

RESUMO

Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T-cell function and immunity in older individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here, we evaluated the age-associated immune alterations, particularly in effector and Treg responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N-acetyl-cysteine (NAC) in elderly TB. Higher frequency of Treg cells and reduced IFN-γ positive T cells were observed among older TB patients. The elevated number of Treg cells correlated tightly with bacillary load (i.e. disease severity); which declined significantly in response to successful anti-tubercular treatment. We could rescue Myobacterium tuberculosis-specific effector T cell (Th1) responses through various in vitro approaches, for example, Treg cell depletion and co-culture experiments, blocking experiments using antibodies against IL-10, TGF-ß, and programmed death-1 (PD-1) as well as NAC supplementation. We report old age-associated enrichment of Treg cells and suppression of M. tuberculosis-specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation.


Assuntos
Linfócitos T Reguladores/imunologia , Tuberculose Pulmonar/imunologia , Acetilcisteína/farmacologia , Adolescente , Adulto , Fatores Etários , Idoso , Citocinas/análise , Citocinas/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo , Receptor de Morte Celular Programada 1/fisiologia , Células Th1/imunologia , Fator de Crescimento Transformador beta/fisiologia , Tuberculose Pulmonar/metabolismo , Adulto Jovem
20.
Eur J Immunol ; 50(8): 1237-1240, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32379351

RESUMO

Patients may display alloimmunization following transfusion. Microparticles (MPs) released into the blood are present in transfusion products. We show that MPs can modulate the immune system, CD4+ T-cell, and humoral responses, through their concentration, cellular origin and phenotype, and should therefore be considered to reduce the immune impact of transfusion.


Assuntos
Micropartículas Derivadas de Células/fisiologia , Transfusão de Eritrócitos , Eritrócitos/imunologia , Imunomodulação , Animais , Citocinas/fisiologia , Humanos , Camundongos
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