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1.
Science ; 368(6490)2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32355002

RESUMO

Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand-an adaptive response associated with improved metabolic fitness. We found that the type 2 cytokine interleukin-13 (IL-13) is induced in exercising muscle, where it orchestrates metabolic reprogramming that preserves glycogen in favor of fatty acid oxidation and mitochondrial respiration. Exercise training-mediated mitochondrial biogenesis, running endurance, and beneficial glycemic effects were lost in Il13-/- mice. By contrast, enhanced muscle IL-13 signaling was sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to the effects of exercise training. In muscle, IL-13 acts through both its receptor IL-13Rα1 and the transcription factor Stat3. The genetic ablation of either of these downstream effectors reduced running capacity in mice. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy.


Assuntos
Adaptação Fisiológica/imunologia , Glicogênio/metabolismo , Interleucina-13/metabolismo , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Resistência Física/imunologia , Animais , Glicemia/metabolismo , Linhagem Celular , Ácidos Graxos/metabolismo , Feminino , Humanos , Interleucina-13/sangue , Interleucina-13/genética , Subunidade alfa1 de Receptor de Interleucina-13/genética , Subunidade alfa1 de Receptor de Interleucina-13/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mioblastos/metabolismo , Oxirredução , Condicionamento Físico Animal , Corrida , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
4.
Viruses ; 12(5)2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384820

RESUMO

SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.


Assuntos
Anticorpos Antivirais/imunologia , Testes de Neutralização/métodos , Glicoproteína da Espícula de Coronavírus/análise , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Contenção de Riscos Biológicos , Células HEK293 , Humanos , Lentivirus , Peptidil Dipeptidase A/metabolismo , Plasma/imunologia
5.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 220-226, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391668

RESUMO

OBJECTIVE: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient. METHODS: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3+T, CD4+ T, CD8+ T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored. RESULTS: On D1 of admission, the numbers of peripheral blood CD3+ T, CD4+ T, CD8+ T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3+ T, CD8+ T and CD4 + T cells gradually recovered and showed a linear growth trend (linear fitting equation: Y=18.59X+109.4, P<0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90. CONCLUSIONS: In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Metilprednisolona , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Contagem de Células , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Estado Terminal , Citocinas/sangue , Feminino , Humanos , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Resultado do Tratamento
7.
Emerg Microbes Infect ; 9(1): 900-902, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32380903

RESUMO

Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Betacoronavirus/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva/normas , Pandemias , Fatores de Tempo , Vacinas Virais/normas
10.
Curr Oncol Rep ; 22(5): 53, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385672

RESUMO

PURPOSE OF REVIEW: The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged to be the biggest global health threat worldwide, which has now infected over 1.7 million people and claimed more than 100,000 lives around the world. Under these unprecedented circumstances, there are no well-established guidelines for cancer patients. RECENT FINDINGS: The risk for serious disease and death in COVID-19 cases increases with advancing age and presence of comorbid health conditions. Since the emergence of the first case in Wuhan, China, in December 2019, tremendous research efforts have been underway to understand the mechanisms of infectivity and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a fatal virus responsible for abysmal survival outcomes. To minimize the mortality rate, it becomes prudent to identify symptoms promptly and employ treatments appropriately. Even though no cure has been established, multiple clinical trials are underway to determine the most optimal strategy. Managing cancer patients under these circumstances is rather challenging, given their vulnerable status and the aggressive nature of their underlying disease. In this comprehensive review, we discuss the impact of COVID-19 on health and the immune system of those affected, reviewing the latest treatment approaches and ongoing clinical trials. Additionally, we discuss challenges faced while treating cancer patients and propose potential approaches to manage this vulnerable population during this pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido , Neoplasias/epidemiologia , Neoplasias/imunologia , Pneumonia Viral/epidemiologia , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Mortalidade Hospitalar , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Fatores de Risco
11.
APMIS ; 128(2): 150-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32352605

RESUMO

Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.


Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/imunologia , Fatores de Virulência/imunologia , Virulência/imunologia , Carcinogênese/imunologia , Humanos , Prognóstico , Neoplasias Gástricas/microbiologia
13.
Eur Rev Med Pharmacol Sci ; 24(8): 4537-4538, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32373992

RESUMO

At present, SARS-Cov-2 is spread all over the world, becoming a serious threat to people's health. SARS-Cov-2 has a strong infection, and the mortality rate of severe patients after infection is high, but there is no effective treatment. Mesenchymal stem cells (MSCs) have anti-inflammatory and immunomodulatory functions, which can reduce the occurrence of cytokine storm syndrome and acute respiratory distress syndrome. At the same time, MSCs can reduce the level of pulmonary fibrosis and enhance tissue injury repair. In this short report, combined with the progress of preclinical and clinical research, we comment the efficacy of MSCs in the treatment of COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Animais , Betacoronavirus , Citocinas/efeitos adversos , Citocinas/imunologia , Humanos , Imunomodulação , Pandemias , Fibrose Pulmonar/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia
15.
Molecules ; 25(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365556

RESUMO

The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia. In addition to the pharmacological agonists, also nutritional ligands of PPAR-γ, like curcuma, lemongrass, and pomegranate, possess anti-inflammatory properties through PPAR-γ activation. Here, we review the main synthetic and nutritional PPAR-γ ligands, proposing a dual approach based on the strengthening of the immune system using pharmacological and dietary strategies as an attempt to prevent/treat cytokine storm in the case of coronavirus infection.


Assuntos
Infecções por Coronavirus/patologia , PPAR gama/agonistas , Plantas Medicinais/química , Pneumonia Viral/patologia , Tiazolidinedionas/farmacologia , Animais , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/antagonistas & inibidores , Óleos de Peixe/farmacologia , Humanos , Ligantes , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Alimentos Marinhos/análise , Especiarias/análise
16.
Stem Cell Res Ther ; 11(1): 169, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366290

RESUMO

The outbreak of 2019 novel coronavirus disease (COVID-19) worldwide is becoming rapidly a major concern. The number of severe cases has increased dramatically worldwide, while specific treatment options are scarce. The main pathologic features of severe or critical COVID-19 were consistent with acute lung injure (ALI)/acute respiratory distress syndrome (ARDS), characterized by cellular fibromyxoid exudates, extensive pulmonary inflammation, pulmonary edema, and hyaline membrane formation. Mesenchymal stem cells (MSCs) can balance the inflammatory response and has been mentioned to be effective on ALI/ARDS from both infectious and noninfectious causes previously, presenting an important opportunity to be applied to COVID-19. In this commentary, we summarize the clinical trials of MSCs treatments on ALI/ARDS and raise MSCs as a hopefully alternative therapy for severe or critical COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Lesão Pulmonar Aguda/terapia , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório do Adulto/terapia
17.
J Exp Med ; 217(6)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32353870

RESUMO

The novel 2019 strain of coronavirus is a source of profound morbidity and mortality worldwide. Compared with recent viral outbreaks, COVID-19 infection has a relatively high mortality rate, the reasons for which are not entirely clear. Furthermore, treatment options for COVID-19 infection are currently limited. In this Perspective, we explore the contributions of the innate and adaptive immune systems to both viral control as well as toxicity during COVID-19 infections and offer suggestions to both understand and therapeutically modulate anti-COVID immunity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/terapia , Humanos , Hipóxia/patologia , Hipóxia/terapia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Linfopenia/imunologia , Linfopenia/patologia , Linfopenia/terapia , Macrófagos/imunologia , Macrófagos/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade
18.
Emerg Microbes Infect ; 9(1): 940-948, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32357808

RESUMO

The emerging COVID-19 caused by SARS-CoV-2 infection poses severe challenges to global public health. Serum antibody testing is becoming one of the critical methods for the diagnosis of COVID-19 patients. We investigated IgM and IgG responses against SARS-CoV-2 nucleocapsid (N) and spike (S) protein after symptom onset in the intensive care unit (ICU) and non-ICU patients. 130 blood samples from 38 COVID-19 patients were collected. The levels of IgM and IgG specific to N and S protein were detected by ELISA. A series of blood samples were collected along the disease course from the same patient, including 11 ICU patients and 27 non-ICU patients for longitudinal analysis. N and S specific IgM and IgG (N-IgM, N-IgG, S-IgM, S-IgG) in non-ICU patients increased after symptom onset. N-IgM and S-IgM in some non-ICU patients reached a peak in the second week, while N-IgG and S-IgG continued to increase in the third week. The combined detection of N and S specific IgM and IgG could identify up to 75% of SARS-CoV-2 infected patients in the first week. S-IgG was significantly higher in non-ICU patients than in ICU patients in the third week. In contrast, N-IgG was significantly higher in ICU patients than in non-ICU patients. The increase of S-IgG positively correlated with the decrease of C-reactive protein (CRP) in non-ICU patients. N and S specific IgM and IgG increased gradually after symptom onset and can be used for detection of SARS-CoV-2 infection. Analysis of the dynamics of S-IgG may help to predict prognosis.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Proteínas do Nucleocapsídeo/imunologia , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Idoso , Anticorpos Antivirais/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Cuidados Críticos/estatística & dados numéricos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Glicoproteína da Espícula de Coronavírus/sangue
19.
Medicine (Baltimore) ; 99(18): e19907, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358357

RESUMO

There has been no clear consensus on the optimal consolidation periods following HBeAg seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients. Our study aimed to prospectively compare relapse rates between 12 months' and 18 months' consolidation periods to see whether or not there is beneficial durability of tenofovir disoproxil fumarate (TDF) therapy with longer consolidation periods.We enrolled a total of 137 HBeAg-positive Asian CHB patients treated with TDF monotherapy. Forty-six patients achieved HBeAg SC. Then, they were randomly assigned to consolidation period of either 12 months (group A) or 18 months (group B). After stopping TDF therapy, all patients were followed up for 12 months.Thirteen patients (56.5%) relapsed in group A and 12 patients (52.2%) relapsed in group B after 12 months' follow-up (P = .958). Pretreatment HBsAg level is the only significant predictor for off-therapy recurrence by univariate analysis (P = .024). Baseline HBeAg >1000 S/CO in group B patients were significantly less likely to relapse than those of group A (P = .046). Baseline alanine aminotransferase (ALT) >133 U/L could significantly predict occurrence of HBeAg SC (P = .008; 95% CI: 0.545-0.763; AUC: 0.654).Overall, a prolonged consolidation period has no positive effect on TDF therapy on sustained viral suppression in HBeAg-positive Asian CHB patients. However, a prolonged consolidation period was beneficial to patients with high baseline semi-quantitative HBeAg levels in terms of off-treatment durability. Baseline ALT > 133 U/L could significantly predict the occurrence of HBeAg SC.


Assuntos
Antivirais/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Tenofovir/administração & dosagem , Adulto , Alanina Transaminase/sangue , Esquema de Medicação , Feminino , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Soroconversão/efeitos dos fármacos , Resposta Viral Sustentada , Fatores de Tempo
20.
Nat Commun ; 11(1): 2251, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366817

RESUMO

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/farmacologia , Afinidade de Anticorpos/imunologia , Betacoronavirus/química , Betacoronavirus/efeitos dos fármacos , Chlorocebus aethiops , Sequência Conservada , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Humanos , Técnicas In Vitro , Concentração Inibidora 50 , Modelos Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos/imunologia , Receptores Virais/química , Receptores Virais/metabolismo , Vírus da SARS/química , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
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