Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chin Med J (Engl) ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32004165

RESUMO

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

2.
Mil Med Res ; 7(1): 4, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029004

RESUMO

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Infecção Hospitalar , Controle de Infecções , Programas de Rastreamento , Equipamento de Proteção Individual , Pneumonia Viral , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Diagnóstico Diferencial , Medicamentos de Ervas Chinesas , Medicina Baseada em Evidências , Hidratação , Humanos , Controle de Infecções/normas , Pulmão/diagnóstico por imagem , Epidemiologia Molecular , Cuidados de Enfermagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
4.
Cell Physiol Biochem ; 50(2): 757-767, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30308508

RESUMO

BACKGROUNDS/AIMS: Epithelial-to-mesenchymal transition (EMT) has been proven to be involved in development and progression of pulmonary fibrosis. This study aims to investigate the role of transforming growth factor ß1 (TGFß1)-smad signaling pathway in the interleukin-33 (IL-33) induced EMT. METHODS: The human type II alveolar epithelial cell line, A549, and small airway epithelial cells (SAEC) were cultured and divided into 4 groups including Control, LY-2109761 (TGFß receptor inhibitor), IL-33 and IL-33+LY-2109761 group. Expression of TGFß1, E-cadherin (E-cad) and α-smooth muscle actin (α-SMA) were examined by using real-time PCR (RT-PCR) and western blot assay, respectively. The smad3 signaling pathway factors, including smad3 and phosphorylated smad3 (p-smad3), were also detected by using western blot assay. RESULTS: IL-33 significantly activated T1/ST2 expression in A549 cells (P< 0.05). TGFß1 receptor inhibitor significantly suppressed the IL-33 caused down-expression of E-cad compared to IL-33 alone (P< 0.05). IL-33 significantly increased the α-SMA levels compared to Control group (P< 0.05) and TGFß1 receptor inhibitor inhibited the other effects of IL-33. IL-33 significantly enhanced the levels of TGFß1 compared to Control group (P< 0.05). TGFß1 receptor inhibitor suppressed the IL-33 induced up-expression of p-smad3. CONCLUSION: The TGFß1-smad signaling pathway participates in the IL-33 induced epithelial-to-mesenchymal transition of A549 cells.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Interleucina-33/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células A549 , Actinas/genética , Actinas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad3/metabolismo
5.
Naunyn Schmiedebergs Arch Pharmacol ; 391(7): 695-704, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29666896

RESUMO

Calpains are intracellular calcium-dependent cysteine proteases, which cleave several substrates proteins, have been proven to play important roles in lung fibrosis. The aim of this study was to investigate the effects of calpain on bleomycin (BLM)-induced pulmonary fibrosis. A lung fibrosis mice model was established successfully by intraperitoneal injection of bleomycin. Calpeptin, a highly selective inhibitor of calpain activation, was administered three times weekly after bleomycin injection. Histological examination was used to assess the fibrosis. Quantitative-PCR and Western blotting were used to assess the development of epithelial-mesenchymal transition (EMT). We found calpeptin treatment decreased the BLM-induced EMT-associated markers, such as muscle actin (α-SMA) and collagen-I, while increased E-cadherin (E-cad). Calpeptin also suppressed the activation of transforming growth factor ß1 (TGFß1)-Smad2/3 signaling pathway, which plays crucial role in lung fibrosis and EMT. Furthermore, we found differentiated embryonic chondrocyte-expressed gene 1 (DEC1), an important transcription factor, was upregulated in both patients with idiopathic pulmonary fibrosis and in bleomycin-induced lung fibrosis. DEC1 was suppressed by calpeptin in bleomycin-induced mice model. Collectively, these findings indicated that calpeptin had a potential anti-fibrosis effect, which focus on the development of EMT.


Assuntos
Calpaína/antagonistas & inibidores , Dipeptídeos/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Actinas/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Bleomicina , Caderinas/genética , Calpaína/metabolismo , Colágeno Tipo I/genética , Dipeptídeos/farmacologia , Proteínas de Homeodomínio/genética , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo
6.
PLoS One ; 12(9): e0183972, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28873461

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disease and the epithelial-mesenchymal transition (EMT) may play an important role in the pathogenesis of pulmonary fibrosis. IL-17 is a proinflammatory cytokine which promotes EMT profiles in lung inflammatory diseases. In this study, we investigated the effect of IL-17 on EMT in alveolar epithelial cell line A549 and the role of TGFß1-Smad and ERK signaling pathways in the process. Morphological observation on the cells was performed under inverted microscope. The mRNA and protein expressions of E-cad and α-SMA were detected by quantitative RT-PCR and western blotting. The mRNA and protein expressions of TGF-ß1 were analyzed via quantitative RT-PCR and ELISA. Expressions of Smad2/3, p-Smad2/3, ERK1/2, p-ERK1/2 and p-JNK were examined by western blotting. The results indicated that IL-17 can induce A549 cells to undergo morphological changes and phenotypic markers changes, such as down-regulated E-cad expression and up-regulated α-SMA expression. Additionally, IL-17 enhanced TGF-ß1 expression and stimulated Smad2/3 and ERK1/2 phosphorylation in A549 cells. However, there were no significant differences in the expression of phosphorylated JNK in A549 cells with or without IL-17 treatment. SB431542 or U0126 treated cells showed inhibited morphological changes and phenotypic markers expression, such as up-regulated E-cad expression and down-regulated α-SMA expression. In summary, our results suggest that IL-17 can induce A549 alveolar epithelial cells to undergo EMT via the TGF-ß1 mediated Smad2/3 and ERK1/2 activation.


Assuntos
Células Epiteliais/citologia , Interleucina-17/metabolismo , Células-Tronco Mesenquimais/citologia , Alvéolos Pulmonares/citologia , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células A549 , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , MAP Quinase Quinase 4/metabolismo , Fosforilação , Fibrose Pulmonar/metabolismo , RNA Mensageiro/metabolismo , Proteína Smad2/metabolismo
7.
Am J Transl Res ; 9(3): 1402-1409, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386365

RESUMO

Cell proliferation, transformation, and epithelial-mesenchymal transition (EMT) are key processes involved in the development of idiopathic pulmonary fibrosis (IPF). This study investigated the regulatory factors and signaling pathways that mediate EMT in the human type II alveolar epithelial A549 cell line. A549 cells were cultured in RPMI-1640 medium and allocated to the following four groups: blank control group or treated with transforming growth factor-ß1 (TGF-ß1), TGF-ß1 + PD 150606 (a calpain 1 inhibitor), or PD 150606. We examined E-cadherin (E-cad), α-smooth muscle actin (α-SMA), and calpain 1 mRNA transcript and protein expression levels in these four groups by performing RT-PCR and western blot analyses. The results indicated that TGF-ß1 treatment significantly downregulated E-cad and upregulated α-SMA expression compared with that of the blank control group (P<0.05). TGF-ß1 also enhanced calpain 1 expression compared with that of the blank control group (P<0.05). By contrast, treatment with the calpain 1 inhibitor PD 150606 increased E-cad expression and decreased α-SMA expression. Furthermore, PD 150606 treatment antagonized TGF-ß1-mediated increase in Akt/phospho-Akt in A549 epithelial cells. However, TGF-ß1-induced ETM was not correlated with the ERK and JNK signaling pathways. These combined results indicate that calpain 1 could regulate EMT in TGF-ß1-treated A549 epithelial cells via the PI3K/Akt signaling pathway.

8.
Exp Ther Med ; 12(6): 4055-4060, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28105134

RESUMO

Allergic asthma is a chronic airway disorder mediated by Th2 cells. It has been shown that IL-9-producing CD8+ cytotoxic T (Tc9) cells promote the subsequent onset of allergic airway inflammation in mice mediated by abnormal Th2 immunity. Whether Tc9 cells are associated with the immunopathogenesis of asthmatic patients remains unknown. In the present study, peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque gradient centrifugation from all subjects. The frequency of Tc9 cells was measured by flow cytometry. Serum IL-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expression levels of IL-9, STAT6, and IRF4 in PBMCs from healthy controls and asthmatic patients were detected by reverse transcription-quantitative polymerase chain reaction. The results showed that the numbers of Tc9 cells in allergic asthmatics were significantly increased, compared with healthy controls (P<0.0001). Notably, IL-9 protein and mRNA levels were increased in allergic asthmatics and STAT6 and IRF4 mRNA levels were elevated, as compared with healthy controls. In addition, circulating numbers of Tc9 cells were positively correlated with blood eosinophil counts and fractioned exhaled nitric oxide (FeNO) levels in asthmatic patients. Moreover, the number of Tc9 cells and serum IL-9 levels in asthmatic patients were significantly decreased after treatment with glucocorticoids (P<0.05). These findings suggest that increased circulating Tc9 cells are associated with eosinophilia and high FeNO of allergic asthma, and that abnormal Tc9 immunity may contribute to the pathogenesis of allergic asthmatics.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA