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2.
Front Immunol ; 12: 594330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828547

RESUMO

Cigarette smoke (CS)-induced macrophage activation and airway epithelial injury are both critical for the development of chronic obstructive pulmonary disease (COPD), while the eventual functions of autophagy in these processes remain controversial. We have recently developed a novel COPD mouse model which is based on the autoimmune response sensitized by CS and facilitated by elastin. In the current study, we therefore utilized this model to investigate the roles of autophagy in different stages of the development of bronchitis-like airway inflammation. Autophagic markers were increased in airway epithelium and lung tissues, and Becn+/- or Lc3b-/- mice exhibited reduced neutrophilic airway inflammation and mucus hyperproduction in this COPD mouse model. Moreover, treatment of an autophagic inhibitor 3-methyladenine (3-MA) either during CS-initiated sensitization or during elastin provocation significantly inhibited the bronchitis-like phenotypes in mice. Short CS exposure rapidly induced expression of matrix metallopeptidase 12 (MMP12) in alveolar macrophages, and treatment of doxycycline, a pan metalloproteinase inhibitor, during CS exposure effectively attenuated the ensuing elastin-induced airway inflammation in mice. CS extract triggered MMP12 expression in cultured macrophages, which was attenuated by autophagy impairment (Becn+/- or Lc3b-/-) or inhibition (3-MA or Spautin-1). These data, taken together, demonstrate that autophagy mediates both the CS-initiated MMP12 activation in macrophages and subsequent airway epithelial injury, eventually contributing to development COPD-like airway inflammation. This study reemphasizes that inhibition of autophagy as a novel therapeutic strategy for CS-induced COPD.


Assuntos
Autofagia , Bronquite/etiologia , Bronquite/metabolismo , Elastina/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Biomarcadores , Bronquite/patologia , Linhagem Celular , Células Cultivadas , Modelos Animais de Doenças , Suscetibilidade a Doenças , Elastina/genética , Expressão Gênica , Humanos , Imuno-Histoquímica , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Camundongos
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1326-1331, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798421

RESUMO

OBJECTIVE: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes. METHODS: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation. RESULTS: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03). CONCLUSION: Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.


Assuntos
Trombocitemia Essencial , Medula Óssea , Calreticulina/genética , China , Humanos , Janus Quinase 2/genética , Masculino , Mutação , Receptores de Trombopoetina/genética
4.
Zhonghua Yi Xue Za Zhi ; 93(37): 2946-9, 2013 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-24401580

RESUMO

OBJECTIVE: To investigate the effect of central venous blood oxygen saturation (ScvO2) and venous-arterial PCO2 (P(cv-a)CO2) guided fluid therapy on tissue perfusion, gastrointestinal function recovering and outcome of the patients who undergoing open gastrointestinal surgery. METHODS: Forty patients undergoing open gastrointestinal surgery were randomly divided into 2 groups (n = 20 each): ScvO2 guided fluid therapy (group S) and P(cv-a) CO2 guided fluid therapy (group P). All the patients were infused 10 ml/kg lactated Ringer's (LR) solution before anesthesia induction, they were all also given a continuous lactated Ringer's (LR) solution's infusion at the speed of 2 ml·kg(-1)·h(-1) during the operation. While, 6%HES 130/0.4 (free flex 6%HES 130/0.4, Fresenius Kabi) infusion was different between the 2 groups, when the patients of group S's central venous blood oxygen saturation < 75% or venous-arterial PCO2 in the patients of P group ≥6 mm Hg, then infused 6%HES 130/0.4. Arterial and central venous blood gas analyses were performed every 20 minutes after skin incision, measure the venous and arterial lactate value, and record the anal exhaust time after surgery, postoperative complications and mortality in 28 days. RESULTS: Compared with group S, the arterial lactate value in T4 (after operation began 80 min) were significantly decreased in group P (P = 0.013), and venous lactate value in T5 (after operation began 100 min) were also lower (P = 0.044), other lactate value were not different (P > 0.05) . The anal exhaust time was not different between the two groups (P = 0.673). All the patients were survival, and there were no obvious postoperative complications. CONCLUSION: Compared to group S, there was a transient improvement in tissue perfusion in group P, but there were no difference in complications and mortality.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Hidratação/métodos , Laparotomia , Idoso , Gasometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório
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