Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.083
Filtrar
1.
Exp Cell Res ; 395(2): 112204, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32735892

RESUMO

BACKGROUND: SARS-CoV2, the agent responsible for the current pandemic, is also causing respiratory distress syndrome (RDS), hyperinflammation and high mortality. It is critical to dissect the pathogenetic mechanisms in order to reach a targeted therapeutic approach. METHODS: In the present investigation, we evaluated the effects of SARS-CoV2 on human bronchial epithelial cells (HBEC). We used RNA-seq datasets available online for identifying SARS-CoV2 potential genes target on human bronchial epithelial cells. RNA expression levels and potential cellular gene pathways have been analyzed. In order to identify possible common strategies among the main pandemic viruses, such as SARS-CoV2, SARS-CoV1, MERS-CoV, and H1N1, we carried out a hypergeometric test of the main genes transcribed in the cells of the respiratory tract exposed to these viruses. RESULTS: The analysis showed that two mechanisms are highly regulated in HBEC: the innate immunity recruitment and the disassembly of cilia and cytoskeletal structure. The granulocyte colony-stimulating factor (CSF3) and dynein heavy chain 7, axonemal (DNAH7) represented respectively the most upregulated and downregulated genes belonging to the two mechanisms highlighted above. Furthermore, the carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) that codifies for a surface protein is highly specific of SARS-CoV2 and not for SARS-CoV1, MERS-CoV, and H1N1, suggesting a potential role in viral entry. In order to identify potential new drugs, using a machine learning approach, we highlighted Flunisolide, Thalidomide, Lenalidomide, Desoximetasone, xylazine, and salmeterol as potential drugs against SARS-CoV2 infection. CONCLUSIONS: Overall, lung involvement and RDS could be generated by the activation and down regulation of diverse gene pathway involving respiratory cilia and muscle contraction, apoptotic phenomena, matrix destructuration, collagen deposition, neutrophil and macrophages recruitment.


Assuntos
Brônquios/metabolismo , Infecções por Coronavirus/genética , Redes Reguladoras de Genes , Pneumonia Viral/genética , Mucosa Respiratória/metabolismo , Transcriptoma , Brônquios/patologia , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Infecções por Coronavirus/metabolismo , Descoberta de Drogas/métodos , Dineínas/genética , Dineínas/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Imunidade Inata , Aprendizado de Máquina , Pandemias , Pneumonia Viral/metabolismo , Regulação para Cima
2.
Exp Cell Res ; 395(2): 112204, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: covidwho-680000

RESUMO

BACKGROUND: SARS-CoV2, the agent responsible for the current pandemic, is also causing respiratory distress syndrome (RDS), hyperinflammation and high mortality. It is critical to dissect the pathogenetic mechanisms in order to reach a targeted therapeutic approach. METHODS: In the present investigation, we evaluated the effects of SARS-CoV2 on human bronchial epithelial cells (HBEC). We used RNA-seq datasets available online for identifying SARS-CoV2 potential genes target on human bronchial epithelial cells. RNA expression levels and potential cellular gene pathways have been analyzed. In order to identify possible common strategies among the main pandemic viruses, such as SARS-CoV2, SARS-CoV1, MERS-CoV, and H1N1, we carried out a hypergeometric test of the main genes transcribed in the cells of the respiratory tract exposed to these viruses. RESULTS: The analysis showed that two mechanisms are highly regulated in HBEC: the innate immunity recruitment and the disassembly of cilia and cytoskeletal structure. The granulocyte colony-stimulating factor (CSF3) and dynein heavy chain 7, axonemal (DNAH7) represented respectively the most upregulated and downregulated genes belonging to the two mechanisms highlighted above. Furthermore, the carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) that codifies for a surface protein is highly specific of SARS-CoV2 and not for SARS-CoV1, MERS-CoV, and H1N1, suggesting a potential role in viral entry. In order to identify potential new drugs, using a machine learning approach, we highlighted Flunisolide, Thalidomide, Lenalidomide, Desoximetasone, xylazine, and salmeterol as potential drugs against SARS-CoV2 infection. CONCLUSIONS: Overall, lung involvement and RDS could be generated by the activation and down regulation of diverse gene pathway involving respiratory cilia and muscle contraction, apoptotic phenomena, matrix destructuration, collagen deposition, neutrophil and macrophages recruitment.


Assuntos
Brônquios/metabolismo , Infecções por Coronavirus/genética , Redes Reguladoras de Genes , Pneumonia Viral/genética , Mucosa Respiratória/metabolismo , Transcriptoma , Brônquios/patologia , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Infecções por Coronavirus/metabolismo , Descoberta de Drogas/métodos , Dineínas/genética , Dineínas/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Imunidade Inata , Aprendizado de Máquina , Pandemias , Pneumonia Viral/metabolismo , Regulação para Cima
4.
Toxicol Lett ; 332: 155-163, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32645460

RESUMO

Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects might result in accumulation of dysfunctional organelles and damaged proteins thus promoting tumorigenesis. In the present study, we found that chronic exposure of human bronchial epithelial BEAS-2B cells to sub-lethal dose of sodium arsenite led to autophagy activation and induced an epithelial-to-mesenchymal transition (EMT) to enhance cell migratory and invasive capability. The malignant transformation was mediated via activation of MEK/ERK1/2 signaling. Importantly, inhibition of autophagy in these arsenic-exposed cells by pharmacological intervention or genetic deletion further promoted the EMT and increased the generation of inflammasomes. Both autophagy inhibitor and genetic deletion of autophagy core gene Beclin-1 produced similar effects. These results may suggest the important role of autophagy in sodium arsenite-induced lung tumorigenesis which may serve as a potential target in prevention and treatment of arsenic-imposed lung cancer.


Assuntos
Arsênico/toxicidade , Autofagia/fisiologia , Brônquios/patologia , Neoplasias Brônquicas/induzido quimicamente , Neoplasias Brônquicas/patologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
5.
Pneumologie ; 74(7): 456-466, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32674192

RESUMO

Cryosurgery has been successfully in bronchoscopy for several years. In addition to the local therapy of tumors and stenoses, cryo extraction enables the endobronchial and transbronchial extraction of large, high-quality biopsies. This is with regard to the diagnosis of diffuse lung diseases and the molecular analysis of malignant lung tumors of outstanding importance. This article explains the method and implementation of transbronchial cryobiopsy.


Assuntos
Biópsia/instrumentação , Brônquios/patologia , Broncoscopia/métodos , Criocirurgia/métodos , Pulmão/patologia , Biópsia/métodos , Humanos , Pneumopatias/diagnóstico , Pneumologia/métodos
6.
J Renin Angiotensin Aldosterone Syst ; 21(2): 1470320320928872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32490715

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. METHODS: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. RESULTS: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. CONCLUSION: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.


Assuntos
Betacoronavirus/fisiologia , Brônquios/patologia , Infecções por Coronavirus/genética , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Inflamação/genética , Pneumonia Viral/genética , Sistema Renina-Angiotensina/genética , Análise por Conglomerados , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Inflamação/patologia , Modelos Lineares , Pandemias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
J Allergy Clin Immunol ; 146(2): 315-324.e7, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32531372

RESUMO

BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.


Assuntos
Asma/epidemiologia , Asma/genética , Infecções por Coronavirus/epidemiologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Receptores Virais/genética , Adolescente , Adulto , Asma/classificação , Asma/imunologia , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Brônquios/imunologia , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Coortes , Infecções por Coronavirus/virologia , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interferon gama/genética , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/virologia , Mapeamento de Interação de Proteínas , Receptores Virais/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Linfócitos T/classificação , Linfócitos T/imunologia , Linfócitos T/patologia , Transcriptoma , Estados Unidos/epidemiologia
8.
J Allergy Clin Immunol ; 146(2): 315-324.e7, 2020 08.
Artigo em Inglês | MEDLINE | ID: covidwho-592253

RESUMO

BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.


Assuntos
Asma/epidemiologia , Asma/genética , Infecções por Coronavirus/epidemiologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Receptores Virais/genética , Adolescente , Adulto , Asma/classificação , Asma/imunologia , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Brônquios/imunologia , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Coortes , Infecções por Coronavirus/virologia , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interferon gama/genética , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/virologia , Mapeamento de Interação de Proteínas , Receptores Virais/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Linfócitos T/classificação , Linfócitos T/imunologia , Linfócitos T/patologia , Transcriptoma , Estados Unidos/epidemiologia
9.
J Renin Angiotensin Aldosterone Syst ; 21(2): 1470320320928872, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-543313

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. METHODS: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. RESULTS: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. CONCLUSION: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.


Assuntos
Betacoronavirus/fisiologia , Brônquios/patologia , Infecções por Coronavirus/genética , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Inflamação/genética , Pneumonia Viral/genética , Sistema Renina-Angiotensina/genética , Análise por Conglomerados , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Inflamação/patologia , Modelos Lineares , Pandemias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
J Vis Exp ; (159)2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32478724

RESUMO

For toxicity testing of airborne particles, air-liquid interface (ALI) exposure systems have been developed for in vitro tests in order to mimic realistic exposure conditions. This puts specific demands on the cell culture models. Many cell types are negatively affected by exposure to air (e.g., drying out) and only remain viable for a few days. This limits the exposure conditions that can be used in these models: usually relatively high concentrations are applied as a cloud (i.e., droplets containing particles, which settle down rapidly) within a short period of time. Such experimental conditions do not reflect realistic long-term exposure to low concentrations of particles. To overcome these limitations the use of a human bronchial epithelial cell line, Calu-3 was investigated. These cells can be cultured at ALI conditions for several weeks while retaining a healthy morphology and a stable monolayer with tight junctions. In addition, this bronchial model is suitable for testing the effects of repeated exposures to low, realistic concentrations of airborne particles using an ALI exposure system. This system uses a continuous airflow in contrast to other ALI exposure systems that use a single nebulization producing a cloud. Therefore, the continuous flow system is suitable for repeated and prolonged exposure to airborne particles while continuously monitoring the particle characteristics, exposure concentration, and delivered dose. Taken together, this bronchial model, in combination with the continuous flow exposure system, is able to mimic realistic, repeated inhalation exposure conditions that can be used for toxicity testing.


Assuntos
Ar , Brônquios/patologia , Células Epiteliais/patologia , Exposição por Inalação/análise , Modelos Biológicos , Material Particulado/toxicidade , Testes de Toxicidade , Automação , Técnicas de Cultura de Células , Linhagem Celular , Impedância Elétrica , Células Epiteliais/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Nanoestruturas/toxicidade
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(3): 220-227, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32389169

RESUMO

Objective To investigate whether the recombinant pyrin domain protein can alleviate the airway inflammation and airway remodeling of OVA-induced mice with chronic asthma by inhibiting transforming growth factor ß1(TGF-ß1)/SMAD and Jagged1/Notch1 signaling pathways. Methods Thirty-two male BALB/c mice were selected and divided into 4 groups with 8 mice in each group. The four groups were the control group, OVA model group, recombinant pyrin domain protein treatment group (100 µg/kg), and the dexamethasone treatment group (1 mg/kg). Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression of inflammatory factors in bronchoalveolar lavage fluid (BALF) of mice in each group. hematoxylin-eosin staining (HE) was used to observe the inflammatory infiltration of bronchus in mice. The changes of goblet cells were observed by periodic acid-Schiff (PAS) staining and collagen fibers by Masson staining. Immunohistochemical staining (IHC) was performed to observe the expression distribution of α smooth muscle actin (α-SMA), TGF-ß1 and Notch1 proteins in lung tissues. Western blotting was used to detect the protein levels of α-SMA, E-cadherin, TGF-ß1, SMAD2/3, SMAD7, Jagged1, Notch1 and Hes1 in lung tissues. Results The recombinant pyrin domain protein not only improved the airway inflammatory response of the OVA-induced mice with bronchial asthma, but also inhibited the hyperplasia of goblet cells and collagen fiber deposition, reduced the tumor necrosis factor α (TNF-α) in BALF, interleukin 1ß (IL-1ß), IL-4, IL-13 levels, and inhibited the protein expression of TGF-ß1, SMAD2/3, Jagged1, Notch1, Hes1 and α-SMA in lung tissues. Conclusion The recombinant pyrin domain protein can reduce the airway inflammation and airway remodeling of asthmatic mice by inhibiting TGF-ß1/SMAD and Jagged1/Notch1 signaling pathways.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Domínio Pirina , Proteínas Recombinantes/uso terapêutico , Transdução de Sinais , Animais , Brônquios/patologia , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Inflamação , Proteína Jagged-1 , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Receptor Notch1 , Proteínas Smad , Fator de Crescimento Transformador beta1
12.
Mol Immunol ; 123: 18-25, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32388106

RESUMO

INTRODUCTION: Asthma is a worldwide problem that is caused by complex underlying immune dysregulation. The identification of potential prognostic markers of asthma may provide information for treatment. The purpose of this study was to explore the key mechanisms involved in the development of asthma on the basis of microarray analysis. METHODS: The expression profile data of GSE43696, which contains 20 endobronchial epithelial brushing samples from healthy patients and 88 from asthma patients, were obtained from Gene Expression Omnibus. For the present study, we built co-expression modules by weighted gene co-expression network analysis (WGCNA). This new analysis strategy was applied to the data set to investigate the relationships underlying the modules and the pathogenesis of asthma. Functional enrichment analysis was performed on these co-expression genes from the modules, and a gene network was then constructed. In addition, mouse models of HDM-induced and OVA-induced asthma were established, and the expression of hub genes was measured. RESULTS: First, using WGCNA, 20 co-expression modules were constructed with 19,596 genes obtained from 108 human endobronchial epithelial brushing samples. The number of genes within the modules ranged from 41 to 845. According to the colours assigned by the system, the module positively correlated with asthma status was named 'red module', and the module positively correlated with asthma severity was named 'purple module'. The results of a functional enrichment analysis showed that the red module was mainly enriched in intracellular calcium-activated chloride channel activity, intracellular chloride channel activity and endopeptidase inhibitor activity. The purple module was mainly enriched in microtubule motor activity and microtubule-binding and motor activity. Moreover, the mRNA expression levels of the 15 hub genes were confirmed to be significantly upregulated in the HDM mouse model, and 12 hub genes were upregulated in the OVA model. CONCLUSIONS: The hub genes ANO7, PYCR1 and UBE2C might play potential roles in the pathogenesis of asthma. Our findings provided a framework of co-expression gene modules of asthma and led to the identification of some new markers that might be potential targets for the development of new drugs and diagnostic markers.


Assuntos
Asma/genética , Asma/patologia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Adulto , Animais , Biomarcadores/análise , Brônquios/metabolismo , Brônquios/patologia , Células Cultivadas , Estudos de Coortes , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Índice de Gravidade de Doença , Transdução de Sinais/genética , Adulto Jovem
13.
Nature ; 583(7818): 834-838, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32408338

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies1,2. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/virologia , Mesocricetus/virologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Aerossóis , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Antígenos Virais/isolamento & purificação , Antígenos Virais/metabolismo , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/metabolismo , Brônquios/patologia , Brônquios/virologia , Infecções por Coronavirus/imunologia , Duodeno/virologia , Fômites/virologia , Abrigo para Animais , Rim/virologia , Masculino , Mesocricetus/imunologia , Mucosa Nasal/virologia , Pandemias , Pneumonia Viral/imunologia , RNA Viral/análise , Carga Viral , Perda de Peso
14.
J Bras Pneumol ; 46(2): e20180183, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32402011

RESUMO

OBJECTIVE: To determine the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in non-neoplastic patients with isolated intrathoracic lymphadenopathy (IL). METHODS: This was a retrospective study of patients with isolated IL referred for EBUS-TBNA. We calculated the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of EBUS-TBNA in the diagnosis of granulomatous, reactive, and neoplastic lymphadenopathy. In cases of nonspecific granulomas, reactive lymphadenopathy, or inconclusive results, a definitive diagnosis was established by other diagnostic procedures or during a follow-up period of at least 18 months. RESULTS: Among the 58 patients included in the study, EBUS-TBNA established a diagnosis of granulomatous disease in 22 (38%), reactive lymphadenopathy in 15 (26%), cancer in 8 (14%), and other diseases in 3 (5%). Results were inconclusive in 10 (17%), the diagnosis being established by other bronchoscopic procedures in 2 (20%) and by surgical procedures in 8 (80%). A final diagnosis of reactive lymphadenopathy was established in 12. Of those, 11 (92%) had their diagnosis confirmed during follow-up and 1 (8%) had their diagnosis confirmed by mediastinoscopy. In another 3, a final diagnosis of sarcoidosis or neoplasm was established. For the diagnosis of granulomatous disease, neoplasms, and reactive lymphadenopathy, EBUS-TBNA was found to have a sensitivity of 73%, 68%, and 92%, respectively; a specificity of 100%, 100%, and 93%, respectively; an accuracy of 86%, 93%, and 93%, respectively; a PPV of 100%, 100%, and 80%, respectively; and an NPV of 78%, 92%, and 98%, respectively. CONCLUSIONS: In non-neoplastic patients, granulomatous disease and reactive lymphadenopathy appear to be common causes of isolated IL. EBUS-TBNA shows promising results as a first-line minimally invasive diagnostic procedure. The results obtained by EBUS-TBNA can be optimized by examining clinical and radiological findings during follow-up or by comparison with the results obtained with other bronchoscopic methods.


Assuntos
Brônquios/diagnóstico por imagem , Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Linfonodos/diagnóstico por imagem , Linfadenopatia/diagnóstico por imagem , Mediastino/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Biópsia por Agulha Fina , Biópsia por Agulha/métodos , Brônquios/patologia , Humanos , Linfonodos/patologia , Linfadenopatia/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Nature ; 583(7818): 834-838, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-261141

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies1,2. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/virologia , Mesocricetus/virologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Aerossóis , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Antígenos Virais/isolamento & purificação , Antígenos Virais/metabolismo , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/metabolismo , Brônquios/patologia , Brônquios/virologia , Infecções por Coronavirus/imunologia , Duodeno/virologia , Fômites/virologia , Abrigo para Animais , Rim/virologia , Masculino , Mesocricetus/imunologia , Mucosa Nasal/virologia , Pandemias , Pneumonia Viral/imunologia , RNA Viral/análise , Carga Viral , Perda de Peso
16.
Nature ; 583(7818): 830-833, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-220333

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Pulmão/patologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Transgenes , Animais , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Brônquios/patologia , Brônquios/virologia , Infecções por Coronavirus/imunologia , Modelos Animais de Doenças , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Humanos , Imunoglobulina G/imunologia , Pulmão/imunologia , Pulmão/virologia , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Masculino , Camundongos , Camundongos Transgênicos , Pandemias , Pneumonia Viral/imunologia , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/metabolismo , Replicação Viral , Perda de Peso
17.
Nature ; 583(7818): 830-833, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380511

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Pulmão/patologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Transgenes , Animais , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Brônquios/patologia , Brônquios/virologia , Infecções por Coronavirus/imunologia , Modelos Animais de Doenças , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Humanos , Imunoglobulina G/imunologia , Pulmão/imunologia , Pulmão/virologia , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Masculino , Camundongos , Camundongos Transgênicos , Pandemias , Pneumonia Viral/imunologia , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/metabolismo , Replicação Viral , Perda de Peso
18.
Klin Lab Diagn ; 65(5): 316-320, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32298549

RESUMO

More and more publications appear in the modern literature on the increase in the prevalence of non-tuberculous mycobacteria (NTMs), in particular, representatives of M. chelonae / Mycobacterium abscessus complex (MABSc). The paper presents data on the current classification of M. chelonae / Mycobacterium abscessus complex and its main representatives. The main data on the possible sources and ways of infection of MABSc patients in hospital are presented. The main features of cultivation on various nutrient media and their possible identification using modern methods are also indicated. The main risk factors for the development of mycobacteriosis in patients and the possible clinical picture are described. The prevalence of MABSc representatives in the structure of non-tuberculous mycobacteria isolated from clinical material from 483 patients from the Samara region was assessed for examination for tuberculosis, and the prevalence from 933 patients with cystic fibrosis (CF) from 55 regions of the Russian Federation from 2016 to 2019 was estimated. In total, as a result of the study, 316 NTM strains (65.4%) were isolated and identified in the first group of patients. M.abscessus was isolated and identified 10 strains and 5 strains - M.chelonae, which amounted to 3.2% and 1.6%, respectively, of all NTMs. In general, MABSc representatives were isolated in 3.1% of the examined patients. As a result of a screening study of patients with CF, 14194 microorganism strains from 933 patients were isolated and identified. Altogether M. abscessus was isolated and confirmed from 14 patients of different ages. Thus, the prevalence of MABSc among the examined patients with CF in the Russian Federation was 1.5%.


Assuntos
Brônquios/microbiologia , Pulmão/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium abscessus/classificação , Mycobacterium abscessus/isolamento & purificação , Brônquios/patologia , Humanos , Pulmão/patologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Prevalência , Federação Russa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA