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1.
Cells ; 10(11)2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34831433

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Immune disorders play an important role in IPF pathogenesis. Here, we show that Th9 cells differentiate and activate in the lung tissue of patients with IPF and bleomycin (BLM)-induced lung fibrosis mice. Moreover, we found that Th9 cells promote pulmonary fibrosis in two ways. On the one hand, Th9 cells promote fibroblast differentiation, activation, and collagen secretion by secreting IL-9. On the other hand, they promote differentiation of Th0 cells into Th2 cells by secreting IL-4. Th9 cells and Th2 cells can promote each other, accelerating the Th1/Th2 imbalance and eventually forming a positive feedback of pulmonary fibrosis. In addition, we found that neutralizing IL-9 in both preventive and therapeutic settings ameliorates bleomycin-induced pulmonary fibrosis. Furthermore, we identified several critical signaling pathways involved in the effect of neutralizing IL-9 on pulmonary fibrosis by proteomics study. From an immunological perspective, we elucidated the novel role and underlying mechanism of Th9 cells in pulmonary fibrosis. Our study suggested that Th9-based immunotherapy may be employed as a treatment strategy for IPF.


Assuntos
Fibrose Pulmonar Idiopática/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Anticorpos Neutralizantes/metabolismo , Bleomicina , Estudos de Casos e Controles , Diferenciação Celular , Proliferação de Células , Colágeno/metabolismo , Feminino , Fibroblastos/patologia , Humanos , Fibrose Pulmonar Idiopática/patologia , Interleucina-9/metabolismo , Leucócitos Mononucleares/metabolismo , Pulmão/imunologia , Pulmão/patologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Proteômica , Transdução de Sinais
2.
Sci Rep ; 9(1): 6452, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015608

RESUMO

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.


Assuntos
Algoritmos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Nat Genet ; 49(1): 46-53, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27869827

RESUMO

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ∼1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease.


Assuntos
Cardiomiopatia Dilatada/genética , Conectina/genética , Variação Genética/genética , Coração/fisiologia , Animais , Cardiomiopatia Dilatada/patologia , Estudos de Casos e Controles , Estudos de Coortes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Ratos
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