Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.043
Filtrar
1.
J Ethnopharmacol ; 283: 114701, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34606948

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. AIM OF THE STUDY: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. METHODS: We use TGF-ß1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. RESULTS: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.


Assuntos
COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Fitoterapia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Células RAW 264.7 , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
2.
Indian J Tuberc ; 68(4): 450-456, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34752312

RESUMO

BACKGROUND: Moderate and severe COVID-19 patients typically present with pneumonia. In this study we aimed to detect the occurrence of pulmonary residuals as a late sequela of COVID-19 and to identify it's predictors among moderate and severe cases. METHODS: This observational prospective study involved 85 COVID-19 patients confirmed by real time polymerase chain reaction (RT-PCR) nasopharyngeal swab, patients were recruited in the period of 1 st of June to 1 st of July. Demographic and clinical data were obtained for each patient. Chest imaging was performed initially and after 3 weeks to detect post COVID pulmonary residuals. RESULTS: The study population included 74 (87.1%) moderate and 11 (12.9%) severe patients. Patients with older age, male gender, high BMI and initial chest CT of consolidation/mixed consolidation and ground glass opacities (GGOs) had more frequent post COVID-19 pulmonary residuals (P 0.003, 0.026, 0.031, 0.035) respectively. There was a statistically significant difference between patients who showed complete resolution and patients who developed pulmonary residuals regarding the lymphocyte count, serum CRP and ferritin levels (P 0.0001). After logistic regression, male gender, high BMI, initial chest CT of consolidation/mixed consolidation and GGOs, lymphocytopenia, high serum CRP and ferritin levels were the predictors of pulmonary residuals. While the age wasn't statistically significant. CONCLUSION: 38.5% of moderate and severe COVID-19 patients tend to have pulmonary residuals. Independent predictors of pulmonary residuals as a sequela of COVID-19 are male gender, high BMI, initial chest CT of consolidation and mixed consolidation/GGOs, lymphocytopenia, high serum CRP and ferritin levels.


Assuntos
COVID-19/complicações , COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Fibrose Pulmonar/epidemiologia , SARS-CoV-2/isolamento & purificação , Tórax/diagnóstico por imagem , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/terapia , Teste de Ácido Nucleico para COVID-19 , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Estudos Prospectivos , Fibrose Pulmonar/diagnóstico por imagem , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/genética , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
Front Immunol ; 12: 741218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777353

RESUMO

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical αß T cells. However, another subset of T cells called γδ T cells could have an important role to play. As part of the innate immune system, γδ T cells respond to inflammation and stressed or infected cells. The γδ T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because γδ T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for γδ T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cells in vitro. γδ T cells can take up, process and present antigens from microbes and human cells. As e.g. tumour-associated antigens are presented by MHC on γδ T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. γδ T cells are already used for medical purposes in oncology and have potential in cancer therapy. As γδ T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and γδ T cells.


Assuntos
COVID-19/imunologia , Linfócitos Intraepiteliais/imunologia , SARS-CoV-2 , Animais , Síndrome da Liberação de Citocina/imunologia , Humanos , Neoplasias/imunologia , Fibrose Pulmonar/imunologia
4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 454-459, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816650

RESUMO

Objective: To investigate the effects of simvastatin (SIM) on pulmonary fibrosis and the expression of VE-cadherin(VE-cad),vimentin(VIM) and alpha-smooth muscle actin(α-SMA)in the pulmonary fibrosis tissue of rats. Methods: Sixty healthy male SD rats were randomly divided into control group(group A), bleomycin group(group B), 5 mg SIM group (group C) and 10 mg SIM group (group D),15 rats in each group. The model of rat pulmonary fibrosis was established by itraperitoneal injection of bleomycin(5 mg/kg). Since the first day of modeling, the rats of group C and D were treated with simvastatin suspension 5 mg/(kg·d) and 10 mg/(kg·d) by intragastric administration everyday, and the rats of group A and B were treated with equal volume of saline 10 ml/(kg·d) everyday. Five rats of each group were sacrificed randomly at the 7th, 14th and 28th day. Masson staining was used to observe the morphological changes of lung tissue in rats. The degree of fibrosis in lung tissues of each group was evaluated by the content of hydroxyproline (HYP) . The microvessel density (MVD) was analyzed by immunohistochemistry,The expressions of protein and mRNA of VE-cad, VIM and α-SMA were determined by immunohistochemistry and RT-PCR. Results: ①Compared with group A, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in lung tissues of groups B, C and D were increased significantly at the 7th, 14th and 28th day(all P<0.05), which reached highest level at the 28th day. However, the mRNA and protein expression levels of VE-CAD were decreased significantly at the corresponding time (P<0.05), which reached lowest level at 28th day. ②Compared with group B, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in groups C and D were decreased at the 7th, 14th and 28th day (all P<0.05), which were decreased more obviously in group D at the 28th day. However, the mRNA and protein expression levels of VE-CAD were increased at the corresponding time (all P<0.05), which were increased more obviously in group D at the 28th day. Conclusion: Simvastatin can reduce the degree of pulmonary fibrosis in rats through inhibiting the process of EnMT, which can enhance the expression of VE-cad and reduce the expression of VIM and α-SMA.


Assuntos
Fibrose Pulmonar , Sinvastatina , Animais , Bleomicina , Pulmão , Masculino , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Sinvastatina/farmacologia
5.
Front Immunol ; 12: 740260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745111

RESUMO

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor ß1 (TGF-ß1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-ß1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-ß1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-ß1 mRNA performed at the time of first medical contact.


Assuntos
COVID-19/fisiopatologia , Ventrículos do Coração/patologia , Miocárdio/patologia , Fibrose Pulmonar/fisiopatologia , SARS-CoV-2/fisiologia , Adulto , Idoso , COVID-19/imunologia , Feminino , Fibrose , Ventrículos do Coração/metabolismo , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Neuropilina-1/genética , Neuropilina-1/metabolismo , Fibrose Pulmonar/imunologia , Risco , Índice de Gravidade de Doença , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Carga Viral
6.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 77(11): 1288-1297, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34803109

RESUMO

PURPOSE: This study aimed to perform longitudinal observation using 4D-computed tomography (CT) and compare images acquired by 3D-CT and 3D-ultrashort echo time (UTE) for evaluation of bleomycin-induced lung fibrosis model. METHOD: The pulmonary fibrosis model was induced by instilling intratracheally with 50 µl of bleomycin. 4D-CT images were classified into four phases after acquisition and analyzed. To study the effects of respiratory gating, we aquired 3D-CT and 3D-UTE images with and without respiratory gating. For comparison between CT and UTE images, we performed no-triggerd 3D-CT and 3D-UTE under free-breathing. MR signal intensity ratio and CT values were measured in three regions of the upper, middle, and lower lung. RESULTS: At 4DCT, total lung volume at maximum inspiration (4th phase) decreased significantly compared with control mouse and the ratio of lung volume at inspiration to expiration also showed a significant decrease. In comparison of the images between with and without respiratory gating, clearer images were obtained by respiratory gating. However, there was no significant difference between both. In comparison between CT and UTE images, magnetic resonance (MR) signal intensity ratio and CT value were significantly correlated, but 3D-UTE images showed poor delineation of the lower lung and that near the diaphragm compared with 3D-CT images. CONCLUSION: 4D micro-CT and nontriggered 3D UTE-magnetic resonance imaging (MRI) under free breathing can be useful to evaluate bleomycininduced lung fibrosis model mouse.


Assuntos
Bleomicina , Fibrose Pulmonar , Animais , Imageamento Tridimensional , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Camundongos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/diagnóstico por imagem , Microtomografia por Raio-X
7.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 39(10): 726-732, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34727651

RESUMO

Objective: To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats. Methods: In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-ß1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1ß) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results: Compared with the negative control group, SiO2 model group had a significant decrease in the body weight of rats (P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α, IL-1ß were all significantly increased (P<0.05) . Compared with the SiO2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly (P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α and IL-1ß were significantly decreased (P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased (P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased (P<0.05) . Conclusion: Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.


Assuntos
Metformina , Pneumonia , Fibrose Pulmonar , Animais , Pulmão , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Ratos , Ratos Wistar , Dióxido de Silício , Fator de Crescimento Transformador beta1
8.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 577-583, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821087

RESUMO

Objective: To study the role of Notch-1/Twist-1 axis in the process of epithelial-mesenchymal transition (EMT) of type II alveolar epithelial cells in pulmonary fibrosis (PF) and hope to provide a new theoretical basis for the pathogenesis of PF. Methods: Thirty rats were randomly divided into control group and bleomycin (BLM) group, 15 rats in each group. The PF rat model was induced by intratracheal injection of BLM (7 500 U/kg). Excised inferior lobe of left lung was fixed in 10% formalin for HE staining, Masson staining and transforming growth factor-beta 1 (TGF-ß1) immunohistochemistry staining after BLM injection for 28 days. The cultured type II alveolar epithelial cells (RLE-6TN) were divided into 4 groups (Control group, transforming growth factor-beta 1 (TGF-ß1) group, Notch-1 negative control siRNA (NC siRNA, 100 pmol/L) group and Notch-1 siRNA (100 pmol/L) group), each group was established nine holes. The cells were treated with TGF-ß1 (5.0 ng/ml) for 24 h following NC siRNA or Notch-1 siRNA for 48 h. The mRNA and (or) proteins levels of TGF-ß1, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), Vimentin, E-Cadherin, Notch-1, Notch-1 intracellular domain (NICD), Hes-1 and Twist-1 were detected in lung tissue and type II alveolar epithelial cells. Results: In vivo, compared with the control group, the alveolar atrophy, collapse and fusion occurred, alveolar septum widened significantly, and a large number of inflammatory cells infiltrated in the pulmonary interstitial of the rats in the BLM group. And compared with control group, BLM obviously increased collagen deposition and collagen I and collagen III expressions, while the expressions of ZO-1 and E-cadherin were decreased, and the expressions of Vimentin and N-cadherin were increased, and concomitantly with increasing Notch-1, NICD, Hes-1 and Twist-1 expression in lung tissues of rats (P<0.01). In vitro, compared with control group, TGF-ß1 treatment obviously induced collagen I, collagen III, Notch-1, NICD, Hes-1 and Twist-1 expressions, and the expressions of E-cadherin and ZO-1 were decreased and the expressions of Vimentin and N-cadherin were increased(P<0.01). Compared with TGF-ß1 group, Notch-1 siRNA treatment significantly inhibited the expressions of Notch-1, NICD, Hes-1 and Twist-1, and the expressions of E-cadherin and ZO-1 were increased and the expressions of Vimentin and N-cadherin were decreased, and also obviously reduced the expressions of collagen I and collagen III induced by TGF-ß1 (P<0.05 or P<0.01). Conclusion: Notch-1/Twist-1 axis is involved in the EMT process of type II alveolar epithelial cells, suggesting that Notch-1/Twist-1 signaling may be involved in the development of pulmonary fibrosis.


Assuntos
Transição Epitelial-Mesenquimal , Fibrose Pulmonar , Células Epiteliais Alveolares , Animais , Bleomicina , Pulmão , Fibrose Pulmonar/induzido quimicamente , Ratos , Fator de Crescimento Transformador beta1
9.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638771

RESUMO

Peroxisome proliferator-activated receptor gamma (PPARγ) is a type II nuclear receptor, initially recognized in adipose tissue for its role in fatty acid storage and glucose metabolism. It promotes lipid uptake and adipogenesis by increasing insulin sensitivity and adiponectin release. Later, PPARγ was implicated in cardiac development and in critical conditions such as pulmonary arterial hypertension (PAH) and kidney failure. Recently, a cluster of different papers linked PPARγ signaling with another superfamily, the transforming growth factor beta (TGFß), and its receptors, all of which play a major role in PAH and kidney failure. TGFß is a multifunctional cytokine that drives inflammation, fibrosis, and cell differentiation while PPARγ activation reverses these adverse events in many models. Such opposite biological effects emphasize the delicate balance and complex crosstalk between PPARγ and TGFß. Based on solid experimental and clinical evidence, the present review summarizes connections and their implications for PAH and kidney failure, highlighting the similarities and differences between lung and kidney mechanisms as well as discussing the therapeutic potential of PPARγ agonist pioglitazone.


Assuntos
Rim/metabolismo , Pulmão/metabolismo , PPAR gama/metabolismo , Fibrose Pulmonar/metabolismo , Insuficiência Renal/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Animais , Humanos , PPAR gama/agonistas , Pioglitazona/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico
10.
In Vivo ; 35(6): 3053-3066, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34697137

RESUMO

BACKGROUND/AIM: The role of senescence and bone marrow-derived cells in silica-induced pulmonary fibrosis is unknown. MATERIALS AND METHODS: C57BL/6HNsd, p16+/LUC, and tdTOMp16+ mice were intratracheally injected with 200 mg/kg crystalline silica or irradiated (20 Gy) to the thoracic cavity and followed for the development of lung fibrosis. RESULTS: The p16+/LUC mice demonstrated senescence by day 7 after silica exposure. C57BL/6 mice exposed to silica demonstrated upregulation of p16, p21, and tyrosine kinase Fgr by day 7, whereas thoracic irradiation induced p21 and Fgr by day 50 and p16 by day 110. Silica exposed GFP+ bone marrow chimeric C57BL/6 mice demonstrated senescent cells and gfp+/Fgr+ monocyte/macrophages in the lungs on day 21. The Fgr inhibitor TL02-59 abrogated monocyte/macrophages recruitment in in vitro transwell experiments. CONCLUSION: Both silica and radiation exposure induce senescence and upregulate tyrosine kinase Fgr for the recruitment of bone marrow-derived monocyte/macrophages and the development of pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Dióxido de Silício , Animais , Medula Óssea , Senescência Celular , Pulmão , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Monócitos , Fibrose Pulmonar/induzido quimicamente , Dióxido de Silício/toxicidade
11.
PLoS One ; 16(10): e0259153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34705851

RESUMO

PURPOSE: To determine the effects of statins and steroids on the risk of coronary artery disease (CAD) and stroke in patients with interstitial lung disease and pulmonary fibrosis (ILD-PF). METHODS: We retrospectively enrolled patients with ILD-PF who were using statins (statin cohort, N = 11,567) and not using statins (nonstatin cohort, N = 26,159). Cox proportional regression was performed to analyze the cumulative incidence of CAD and stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of CAD and stroke were determined after sex, age, and comorbidities, as well as the use of inhaler corticosteroids (ICSs), oral steroids (OSs), and statins, were controlled for. RESULTS: Compared with those of patients without statin use, the aHRs (95% CIs) of patients with statin use for CAD and ischemic stroke were 0.72 (0.65-0.79) and 0.52 (0.38-0.72), respectively. For patients taking single-use statins but not ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.72 (0.65-0.79)/0.69 (0.61-0.79) and 0.54 (0.39-0.74)/0.50 (0.32-0.79), respectively. For patients using ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.71 (0.42-1.18)/0.74 (0.64-0.85) and 0.23 (0.03-1.59)/0.54 (0.35-0.85), respectively. CONCLUSIONS: The findings demonstrate that statin use, either alone or in combination with OS use, plays an auxiliary role in the management of CAD and ischemic stroke in patients with ILD-PF.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Fibrose Pulmonar/complicações , Esteroides/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/prevenção & controle , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Esteroides/administração & dosagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle
12.
Biochem Pharmacol ; 193: 114812, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34687672

RESUMO

Pulmonary fibrosis (PF) is characterised by several grades of chronic inflammation and collagen deposition in the interalveolar space and is a hallmark of interstitial lung diseases (ILDs). Recently, infectious agents have emerged as driving causes for PF development; however, the role of viral/bacterial infections in the initiation and propagation of PF is still debated. In this context, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has been associated with acute respiratory distress syndrome (ARDS) and PF development. Although the infection by SARS-CoV-2 can be eradicated in most cases, the development of fibrotic lesions cannot be precluded; furthermore, whether these lesions are stable or progressive fibrotic events is still unknown. Herein, an overview of the main molecular mechanisms driving the fibrotic process together with the currently approved and newly proposed therapeutic solutions was given. Then, the most recent data that emerged from post-COVID-19 patients was discussed, in order to compare PF and COVID-19-dependent PF, highlighting shared and specific mechanisms. A better understanding of PF aetiology is certainly needed, also to develop effective therapeutic strategies and COVID-19 pathology is offering one more chance to do it. Overall, the work reported here could help to define new approaches for therapeutic intervention in the diversity of the ILD spectrum.


Assuntos
COVID-19/complicações , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/metabolismo , Animais , COVID-19/etiologia , COVID-19/imunologia , COVID-19/metabolismo , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fibrose Pulmonar/etiologia
13.
Front Immunol ; 12: 687397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671341

RESUMO

Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS)-like hyperinflammation and endothelial dysfunction, that can lead to respiratory and multi organ failure and death. Interstitial lung diseases (ILD) and pulmonary fibrosis confer an increased risk for severe disease, while a subset of COVID-19-related ARDS surviving patients will develop a fibroproliferative response that can persist post hospitalization. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling lysophospholipid with multiple effects in pulmonary and immune cells. In this review, we discuss the similarities of COVID-19, ARDS and ILDs, and suggest ATX as a possible pathologic link and a potential common therapeutic target.


Assuntos
COVID-19/patologia , Diester Fosfórico Hidrolases/metabolismo , Fibrose Pulmonar/patologia , Síndrome do Desconforto Respiratório/patologia , Anti-Inflamatórios/uso terapêutico , COVID-19/sangue , Dexametasona/uso terapêutico , Humanos , Pulmão/patologia , Lisofosfolipídeos/metabolismo , Diester Fosfórico Hidrolases/sangue , Fibrose Pulmonar/sangue , Síndrome do Desconforto Respiratório/sangue , SARS-CoV-2 , Transdução de Sinais/imunologia
14.
Front Immunol ; 12: 735922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671353

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.


Assuntos
COVID-19/mortalidade , COVID-19/patologia , Lesão Pulmonar/patologia , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Linfócitos T CD8-Positivos/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/patologia , Células Epiteliais/patologia , Feminino , Hemorragia/patologia , Humanos , Inflamação/patologia , Pulmão/patologia , Lesão Pulmonar/virologia , Linfopenia/patologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/patologia , Neutrófilos/imunologia , SARS-CoV-2 , Trombose/patologia
15.
Nutrients ; 13(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684599

RESUMO

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as indices of lung function and bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for biomarkers of fibrosis. Mice on phytoestrogen-free diet demonstrated increased mortality and stronger signs of chronic lung injury and pulmonary fibrosis, as reflected in the expression of collagen, extracellular matrix deposition, histology, and lung mechanics, compared to mice on regular diet. We conclude that dietary phytoestrogens play an important role in the pathogenesis of pulmonary fibrosis and suggest that phytoestrogens (e.g., genistein) may be useful as part of a therapeutic regimen against hydrochloric acid-induced lung fibrosis and chronic lung dysfunction.


Assuntos
Dieta , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Fitoestrógenos/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Animais , Doença Crônica , Proteínas da Matriz Extracelular/metabolismo , Ácido Clorídrico , Inflamação/patologia , Contagem de Leucócitos , Pulmão/fisiopatologia , Lesão Pulmonar/complicações , Lesão Pulmonar/mortalidade , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fitoestrógenos/farmacologia , Fibrose Pulmonar/complicações , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
16.
Sci Rep ; 11(1): 19979, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620968

RESUMO

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.


Assuntos
COVID-19/sangue , Mucina-1/sangue , Fibrose Pulmonar/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores/sangue , COVID-19/complicações , COVID-19/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , SARS-CoV-2/isolamento & purificação
17.
BMJ Open ; 11(10): e047039, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635513

RESUMO

OBJECTIVE: To determine the effect of statins on risk of cancer in patients with interstitial lung disease (ILD) and pulmonary fibrosis. SETTING: We retrospectively enrolled patients with ILD and pulmonary fibrosis and divided them into two cohorts by statin use (statin users (n=10 036) and statin non-users (n=10 036)). PARTICIPANTS: We selected patients with ILD and pulmonary fibrosis (N=53 862) from Taiwan's National Health Insurance Research Database. Time-dependent Cox models were used to compare risk of cancer of propensity-matched statin users and non-users. Cumulative cancer incidence was analysed through Cox proportional regression. We calculated adjusted HRs (aHRs) and their 95% CIs for cancer after adjusting for sex, age, comorbidities, and use of inhaled corticosteroids, oral steroids and statins. RESULTS: Compared with statin non-users, the aHRs (95% CIs) for statin users were 0.60 (0.55 to 0.65) for cancer, 0.52 (0.35 to 0.78) for haematological malignancy, 0.52 (0.38 to 0.72) for cancer of the head and neck, 0.73 (0.59 to 0.89) for colorectal cancer, 0.34 (0.26 to 0.43) for liver cancer, 0.39 (0.23 to 0.67) for pancreatic cancer, 0.40 (0.17 to 0.96) for skin cancer, 0.67 (0.52 to 0.87) for breast cancer, 0.27 (0.14 to 0.54) for cervical cancer, 0.37 (0.30 to 0.46) for other immunological cancers, 0.73 (0.54 to 0.98) for bladder/kidney cancer and 0.88 (0.71 to 1.09) for lung cancer. CONCLUSION: Statin use is associated with lower risk of cancer in the ILD and pulmonary fibrosis cohort.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Pulmonares Intersticiais , Neoplasias , Fibrose Pulmonar , Estudos de Coortes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
Adv Respir Med ; 89(5): 477-483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34612504

RESUMO

INTRODUCTION: COVID-19-associated pulmonary sequalae have been increasingly reported after recovery from acute infection. Therefore, we aim to explore the charactersitics of persistent lung parenchymal abnormalities in patients with COVID-19. MATERIAL AND METHODS: An observational study was conducted in patients with post-COVID lung parenchymal abnormalities from April till September 2020. Patients ≥18 years of age with COVID-19 who were diagnosed as post-COVID lung parenchymal abnormality based on respiratory symptoms and HRCT chest imaging after the recovery of acute infection. Data was recorded on a structured pro forma, and descriptive analysis was performed using Stata version 12.1. RESULTS: A total of 30 patients with post-COVID lung parenchymal abnormalities were identified. The mean age of patients was 59.1 (SD 12.6), and 27 (90.0%) were males. Four HRCT patterns of lung parenchymal abnormalities were seen; organizing pneumonia in 10 (33.3%), nonspecific interstitial pneumonitis in 17 (56.7%), usual interstitial pneumonitis in 12 (40.0%) and probable usual interstitial pneumonitis in 14 (46.7%). Diffuse involvement was found in 15 (50.0%) patients, while peripheral predominance in 15 (50.0%), and other significant findings were seen in 8 (26.7%) patients. All individuals were treated with corticosteroids. The case fatality rate was 16.7%. Amongst the survivors, 32.0% recovered completely, 36.0% improved, while 32.0% of the patients had static or progressive disease. CONCLUSION: This is the first study from Southeast Asia that identified post-COVID lung parenchymal abnormalities in patients who had no pre-existing lung disease highlighting the importance of timely recognition and treatment of this entity that might lead to fatal outcome.


Assuntos
COVID-19/diagnóstico por imagem , COVID-19/patologia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Adulto , COVID-19/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , SARS-CoV-2/isolamento & purificação , Tomografia Computadorizada por Raios X
20.
Z Rheumatol ; 80(8): 743-754, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34505934

RESUMO

An interstitial lung disease represents a relevant organ manifestation in many systemic rheumatic diseases (connective tissue disease-interstitial lung disease, CTD-ILD). In 10% of the cases pulmonary fibrosis even results in an underlying systemic disease. The CTD-ILDs are frequently associated with a poor prognosis. Therefore, it is important to test patients with systemic rheumatic diseases timely and regularly for the presence of an ILD. Treatment decisions should be made together with pneumologists and rheumatologists, particularly with respect to the initiation of a specific treatment. Treatment is based on randomized studies only in a few cases and can mostly be derived from case control studies. For systemic sclerosis-associated ILD (SSc-ILD) antifibrotic treatment with nintedanib has also now been approved in addition to an immunosuppressive treatment. For other CTD-ILDs an antifibrotic treatment should be discussed in an interdisciplinary approach depending on the underlying disease corresponding to a progressively fibrosing ILD.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Doenças Reumáticas , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/tratamento farmacológico , Doenças Reumáticas/complicações , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...