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1.
ACS Appl Mater Interfaces ; 16(28): 36063-36076, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38958208

RESUMO

The cell membrane separates the intracellular compartment from the extracellular environment, constraining exogenous molecules to enter the cell. Conventional electroporation typically employs high-voltage and short-duration pulses to facilitate the transmembrane transport of molecules impermeable to the membrane under natural conditions by creating temporary hydrophilic pores on the membrane. Electroporation not only enables the entry of exogenous molecules but also directs the intracellular distribution of the electric field. Recent advancements have markedly enhanced the efficiency of intracellular molecule delivery, achieved through the utilization of microstructures, microelectrodes, and surface modifications. However, little attention is paid to regulating the motion of molecules during and after passing through the membrane to improve delivery efficiency, resulting in an unsatisfactory delivery efficiency and high dose demand. Here, we proposed the strategy of regulating the motion of charged molecules during the delivery process by progressive electroporation (PEP), utilizing modulated electric fields. Efficient delivery of charged molecules with an expanded distribution and increased accumulation by PEP was demonstrated through numerical simulations and experimental results. The dose demand can be reduced by 10-40% depending on the size and charge of the molecules. We confirmed the safety of PEP for intracellular delivery in both short and long terms through cytotoxicity assays and transcriptome analysis. Overall, this work not only reveals the mechanism and effectiveness of PEP-enhanced intracellular delivery of charged molecules but also suggests the potential integration of field manipulation of molecular motion with surface modification techniques for biomedical applications such as cell engineering and sensitive cellular monitoring.


Assuntos
Eletroporação , Eletroporação/métodos , Humanos , Membrana Celular/metabolismo
2.
iScience ; 26(12): 108575, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38125027

RESUMO

The tumor-treating fields (TTFields) technology has revolutionized the management of recurrent and newly diagnosed glioblastoma (GBM) cases. To ameliorate this treatment modality for GBM and other oncological conditions, it is necessary to understand the biophysical principles of TTFields better. In this study, we further analyzed the mechanism of the electromagnetic exposure with varying frequencies and electric field strengths on cells in mitosis, specifically in telophase. In reference to previous studies, an intuitive finite element model of the mitotic cell was built for electromagnetic simulations, predicting a local increase in the cleavage furrow region, which may help explain TTFields' anti-proliferative effects. Cell experiments confirmed that the reduction in proliferation and migration of glioma cell by TTFields was in a frequency- and field-strength-dependent manner. This work provides unique insights into the selection of frequencies in the anti-proliferative effect of TTFields on tumors, which could improve the application of TTFields.

3.
Clin Respir J ; 14(12): 1122-1130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32772499

RESUMO

BACKGROUND AND OBJECTIVE: Platelet activation, inflammatory reactions and oxidative stress are common pathogenesis of chronic obstructive pulmonary disease (COPD) with pulmonary heart disease (PHD). Mean platelet volume (MPV) and red blood cell distribution width (RDW) form part of the pathomechanisms of these conditions. Here, we investigated whether MPV and RDW can be biomarkers of PHD occurring secondary to COPD. MATERIALS AND METHODS: This was a retrospective study on 229 participants with COPD. Among them, 69 had PHD. Complete blood count (CBC), blood gas analysis, pulmonary function tests and echocardiography were analyzed. RESULTS: MPV and RDW-standard deviation (RDW-SD) were significantly higher in patients with PHD than in patients without PHD (P ≤ 0.001). MPV and RDW-SD were positively correlated with pulmonary artery pressure (PAP) and the size of the right ventricle (P ≤ 0.05). Multivariate regression analysis showed that the risk of PHD increased 3-fold per unit rise in MPV (OR = 2.901, P ≤ 0.001). We observed that the risk of PHD increased 1.5 times per unit rise in RDW-SD (OR = 1.371, P ≤ 0.001).The AUC of ROC curve for the combined MPV and RDW-SD in predicting PHD among COPD patients was 0.900 (95%CI: 0.846-0.954, P ≤ 0.001), with a sensitivity of 76.8% and a specificity of 99.4%. CONCLUSIONS: Both MPV and RDW-SD were significantly elevated and correlated with disease severity in COPD patients with PHD. A combination of these two parameters presents an effective biomarker of PHD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Doença Cardiopulmonar , Biomarcadores , Índices de Eritrócitos , Humanos , Volume Plaquetário Médio , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos
4.
Can Respir J ; 2020: 2451703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695244

RESUMO

Background: In recent years, we have observed respiratory difficulty manifested as paroxysmal laryngospasm in a few outpatients, most of whom were first encountered in a respiratory clinic. We therefore explored how to identify and address paroxysmal laryngospasm from the perspective of respiratory physicians. Methods: The symptoms, characteristics, auxiliary examination results, treatment, and prognosis of 12 patients with paroxysmal laryngospasm treated in our hospital from June 2017 to October 2019 were analyzed. Results: Five males (42%) and 7 females (58%) were among the 12 Han patients sampled. The average age of the patients was 49.25 ± 13.02 years. The disease course ranged from 14 days to 8 years and was characterized by sudden dyspnea, an inability to inhale and exhale, a sense of asphyxia, and voice loss during an attack. Eight patients with gastroesophageal reflux were cured after antacid treatment. One case of upper respiratory tract infection (URI) was completely relieved after symptomatic treatment. One patient with left vocal cord paralysis experienced complete relief after specialist treatment by an otorhinolaryngologist. Episodes in 1 patient were significantly reduced after lifestyle improvement. One patient experienced spontaneous relief after rejecting treatment. Conclusions: Paroxysmal laryngospasm is a rare laryngeal disease that generally occurs secondary to gastroesophageal reflux disease (GERD), and antireflux therapy is frequently effective for its treatment. A respiratory physician should master and identify the symptoms and differentiate this condition from hysterical stridor, reflux-related laryngospasm, and asthma. Timely referral to otolaryngologists, gastroenterologists, and other specialists for standardized examination and regular treatment should be provided when necessary.


Assuntos
Antiácidos/uso terapêutico , Gastroenterologistas , Refluxo Gastroesofágico , Comunicação Interdisciplinar , Laringismo , Otorrinolaringologistas , Asma/diagnóstico , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/etiologia , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Laringismo/diagnóstico , Laringismo/etiologia , Laringismo/fisiopatologia , Laringismo/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sons Respiratórios/diagnóstico , Sons Respiratórios/etiologia , Sistema Respiratório/fisiopatologia , Avaliação de Sintomas/métodos , Avaliação de Sintomas/normas
6.
J Mol Med (Berl) ; 97(5): 619-631, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30834948

RESUMO

IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Flow cytometry was performed to identify the cell origin of IL-26. The effects of tuberculosis-specific antigen (ESAT-6/CFP-10) on IL-26 expression of CD4+ T cell were explored. The impacts of IL-26 on modulating CD4+ T cell polarization were also investigated. The concentrations of IL-26 were much higher in tuberculous, malignant, and infectious PE than those in the corresponding serum. The expression of IL-26 on CD4+ T cells was much higher in tuberculous PE than those in the corresponding serum, and pleural Th1 and Th17 cells might be the major cell sources of IL-26. The addition of ESAT-6/CFP-10 to CD4+ T cells led to increasing the number of IL-26-producing CD4+ T cells and IL-26 expression on Th1 and Th17 cells. IL-26 could induce the differentiation and generation of IL-22 by memory and naive CD4+ T cells. IL-26 also upregulated the mRNA encoding CC-chemokine ligand 20 (CCL20) and CCL22 by mononuclear cells isolated from TPE. This study implies that pleural Th1 and Th17 cells are the major cell sources of IL-26, which could induce the differentiation and generation of Th22 cells by CD4+ T cells, suggesting the involvement of IL-26 in the pathogenesis of human TPE. KEY MESSAGES: IL-26 is overexpressed in TPE patients and presents a higher concentration in pleural effusion than the corresponding peripheral blood. Pleural Th1 and Th17 cells might be the major cell sources of IL-26 in TPE patients. IL-26 promotes IL-22 secretion and Th22 generation by CD4+ T cells isolated from TPE patients. IL-26 may play an active role in the pathogenesis of tuberculous pleurisy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Interleucinas/imunologia , Tuberculose Pleural/imunologia , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th17/imunologia , Interleucina 22
7.
Front Immunol ; 10: 220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30842769

RESUMO

The imbalance of CD4+Foxp3+ T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4+CD25-Foxp3+ T cells in immune regulation in COPD remains to be investigated. In the current study, distribution and phenotypic characteristics of CD4+CD25-Foxp3+ T cells from peripheral blood were determined by flow cytometry; the origin, immune function and ultimate fate of CD4+CD25-Foxp3+ T cells were further explored in vitro. It was observed that circulating CD4+CD25-Foxp3+ T cells were significantly increased in stable COPD patients (SCOPD) and resembled central memory or effector memory T cells. Compared with peripheral CD4+CD25+Foxp3+ T cells, peripheral CD4+CD25-Foxp3+ T cells showed a lower expression of Foxp3, CTLA-4, HELIOS, and TIGIT, but a higher expression of CD127 and KI-67, suggesting that CD4+CD25-Foxp3+ T cells lost the expression of Tregs-associated molecules following the reduction in CD25. Unexpectedly, our study found that transforming growth factor-ß1 (TGFß1) decreased CD25 expression and played a critical role in the generation of CD4+CD25-Foxp3+ T cells from CD4+CD25+Foxp3+ T cells. Phenotypic analysis further revealed that both inducible and peripheral CD4+CD25-Foxp3+ T cells exhibited the features of activated conventional T cells. Importantly, memory CD4+CD25-Foxp3+ T cells facilitated the proliferation and differentiation of naïve CD4+ T cells into Th17 cells in the presence of IL-1ß, IL-6, IL-23, and TGFß1. Finally, a fraction of CD4+CD25-Foxp3+ T cells, exhibiting instability and plasticity, were converted to Th17 cells when subjected to Th17 cell-polarizing condition. Taken together, we propose that TGFß1 is responsible for the generation of CD4+CD25-Foxp3+ T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Memória Imunológica , Imunomodulação , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade
8.
Int J Mol Med ; 42(6): 3404-3414, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30320351

RESUMO

In CD4+ T helper (Th) cells, transforming growth factor ß (TGF­ß) is indispensable for the induction of both regulatory T (Treg) and interleukin­17­producing effector T helper (Th17) cells. Although BMP and activin membrane­bound inhibitor (BAMBI) is part of a rheostat­like mechanism for the regulation of TGF­ß signalling and autoimmune arthritis in mouse models, the underlying activity of BAMBI on the human Th17/Treg cell axis, particularly during exposure to cigarette smoke, remains to be elucidated. The present study aimed to further characterize BAMBI expression in human CD4+ cells, as well as immune imbalance during activation and cigarette smoke exposure. Results from the present study indicated that exposure to cigarette smoke extract partially suppressed Treg differentiation and promoted Th17 cell generation under stimulation by anti­CD3/28 antibodies and TGF­ß1. Additionally, exposure to cigarette smoke induced an inhibition of phosphorylated­Smad2/Smad3, which may have arisen from a concomitant enhancement of BAMBI expression. In conclusion, human BAMBI may function as a molecular switch to control TGF­ß signalling strength and the Th17/Treg cell balance, which may be used not only as a biomarker but also as a target of new treatment strategies for maintaining immune tolerance and for the treatment of smoking­induced immune disorders.


Assuntos
Proteínas de Membrana/metabolismo , Fumar/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Adulto , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Proteína Smad3/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
9.
Oncol Lett ; 14(6): 6645-6649, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29151911

RESUMO

The lungs are one of the most common organs to which cancer metastasizes, but are a location not common for uterine sarcoma. A malignant mixed Müllerian tumor (MMMT) of the uterus is an extremely rare and aggressive sarcoma, characterized by a mixture of epithelial and mesenchymal components. There are few reports regarding the pulmonary metastasis from MMMTs. The present study presents the case of a 58-year-old woman with hemoptysis and post-menopausal vaginal bleeding. The woman was initially diagnosed with invasive aspergillosis based on a chest computed tomography (CT) scan showing multiple pulmonary nodular opacities surrounded by a ground-glass attenuation halo (halo-sign). Diagnostic curettage and a percutaneous CT-guided lung biopsy were conducted for the pathological diagnosis. Finally, the diagnosis was confirmed as MMMT with lung metastasis based on the histopathological examination of cervical canals, uterus and lung specimens, which showed a mixture of carcinomatous and sarcomatous elements, and morphology exhibiting hyperchromatic nuclei and necrosis. Immunohistochemical staining was positive for vimentin, focally positive for p16, and negative for napsin, cytokeratin 7 (CK7), CK20, carcinoembryonic antigen, carbohydrate antigen 125, homeobox protein CDX2 and villin in the lung specimens. This case highlights that pulmonary metastatic tumor from uterine sarcoma can present as halo-sign, which is commonly observed in pulmonary aspergillosis. Therefore, it needs to be considered in the differential diagnosis of such lesions, and pathological confirmation is required.

10.
Sci Rep ; 6: 31911, 2016 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-27549738

RESUMO

BMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor ß (TGF-ß) signaling. Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated. In this study, we investigated whether TGF-ß/BAMBI pathway is associated with COPD. Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients. Elevated Th17/Treg ratios, and increased levels of BAMBI protein and mRNA (in plasma and CD4(+) T cells respectively), were observed in COPD compared with HC and HS. BAMBI expression was first observed on human CD4(+) T cells, with a typical membrane-bound pattern. The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-ß1 levels and Th17/Treg ratio. Together, an impaired TGF-ß/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica/imunologia , Transdução de Sinais , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Feminino , Humanos , Masculino , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumar/sangue , Fumar/imunologia , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima
11.
Respir Med Case Rep ; 12: 55-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26029543

RESUMO

Adult lymphoblastic lymphoma (LBL) is an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adult men, accounting for 1% to 2% of all non-Hodgkin's lymphomas. In contrast to B-LBL, T-cell LBL is much more common, accounting for up to 90% of disease in adults. Mediastinal mass, pleural and/or pericardial effusions are the major characteristics of T-LBL. We report an 18-year-old male with a pleural effusion, mediastinal mass, a light pericardial effusion, and a normal hemogram. The cytology of the pleural effusion initially suggested malignancy, but definitive diagnosis was unclear. After a medical thoracoscopy, the partial pleura was picked and immunophenotypic study revealed the following: CD3(+), TdT(+), CD99(+), CD20(-). The patient was finally diagnosed with T-LBL and died only 6 months after that. The case highlight the point that medical thoracoscopy is a safe and accurate diagnostic procedure for pleural diseases, and partial pleura biopsy with immunophenotyping was essential for achieving the correct diagnosis of LBL.

12.
Radiat Res ; 179(4): 485-92, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23421826

RESUMO

Radiation leads to a rapid burst of reactive oxygen species (ROS), which is considered to be one of the major causes of radiation-induced injury. ROS have previously been shown to induce changes in cytosolic Ca²âº ([Ca²âº]i) including [Ca²âº]i oscillation. However, the role of radiation in [Ca²âº]i oscillation is poorly understood. The purpose of this study was to identify the effect of ROS and X ray on [Ca²âº]i oscillation, as well as their role in radiation-induced lung injury. Alveolar macrophages were cultured in the absence and presence of different doses of hydrogen peroxide (H2O2) or exposed to X-ray irradiation with or without pretreatment of diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidases) or tetrandrine (TET, a calcium entry blocker) and cytosolic Ca²âº concentration was detected by fluorescent Ca²âº indicator Fura-2. Rat radiation lung injury was induced in vivo by using 40 Gy X ray and DPI or TET was used to prevent radiation-induced lung injury. The results showed that there was spontaneous [Ca²âº]i oscillation in alveolar macrophages under normal conditions, and treatment of H2O2 (100-500 µM) or 2 Gy X ray inhibited the spontaneous [Ca²âº]i oscillation and induced [Ca²âº]i rise. TET abolished H2O2 or X ray induced [Ca²âº]i rise in alveolar macrophages, and attenuated X ray- induced rat alveolitis in vivo. DPI prevented X-ray-induced inhibition of [Ca²âº]i oscillation in alveolar macrophages and prevented X-ray-induced rat alveolitis. Taken together, the data suggest that the disruption of [Ca²âº]i oscillation and induction of [Ca²âº]i rise through ROS is involved in the mechanism of radiation-induced lung injury.


Assuntos
Sinalização do Cálcio/efeitos da radiação , Macrófagos Alveolares/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Raios X , Animais , Benzilisoquinolinas/farmacologia , Células Cultivadas , Macrófagos Alveolares/metabolismo , Masculino , NADPH Oxidases/antagonistas & inibidores , Oniocompostos/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Respirology ; 16(3): 473-80, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21299686

RESUMO

BACKGROUND AND OBJECTIVE: The diagnosis of tuberculous pleurisy by analysis of pleural fluid using standard diagnostic tools is difficult. Recently, T-cell interferon-γ release assays (IGRA) have been introduced for the diagnosis of tuberculous pleurisy. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of IGRA on both pleural fluid and peripheral blood, for diagnosing tuberculous pleurisy. METHODS: A systematic review was performed of English language publications. Sensitivity, specificity and other measures of the accuracy of IGRA for the diagnosis tuberculous pleurisy using both pleural fluid and blood were pooled using a random-effects model or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance. RESULTS: Seven out of eight studies met the inclusion criteria. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and diagnostic odds ratio were, for pleural fluid: 0.75, 0.82, 3.49, 0.24, 0.85, 0.70 and 19.04, respectively; and for blood: 0.80, 0.72, 2.86, 0.28, 0.78, 0.74 and 11.06, respectively. CONCLUSIONS: As almost 20% of non-tuberculosis patients would be erroneously treated for tuberculosis and 25% of patients with tuberculous pleurisy would be missed, pleural fluid IGRA are not useful for the clinical diagnosis of tuberculous pleurisy.


Assuntos
Interferon gama/imunologia , Linfócitos T/imunologia , Tuberculose Pleural/diagnóstico , Humanos , Interferon gama/sangue , Derrame Pleural/sangue , Derrame Pleural/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Tuberculose Pleural/sangue
14.
J Immunol ; 185(10): 6348-54, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20952674

RESUMO

IL-17-producing CD4(+) T (Th17) cells have been found to be increased in some human cancers; however, the possible implication of Th17 cells in regulating antitumor responses in malignant pleural effusion (MPE) remains to be elucidated. In the current study, distribution and phenotypic features of Th17 cells in both MPE and peripheral blood from patients with lung cancer were determined by flow cytometry or double immunofluorescence staining. The impacts of cytokines on Th17 cell generation and differentiation were explored. The chemoattractant activity of chemokines CCL20 and CCL22 for Th17 cells in vitro was also observed. It was found that the increased Th17 cells could be found in MPE compared with blood. The in vitro experiments showed that IL-1ß, IL-6, IL-23, or their various combinations could promote Th17 cell generation and differentiation from naive CD4(+) T cells. MPE was chemotactic for Th17 cells, and this activity was partly blocked by anti-CCL20 and/or CCL22 Abs. Our data also showed that the accumulation of Th17 cells in MPE predicted improved patient survival. It could be concluded that the overrepresentation of Th17 cells in MPE might be due to Th17 cell differentiation and expansion stimulated by pleural proinflammatory cytokines and to recruitment of Th17 cells from peripheral blood induced by pleural chemokines CCL20 and CCL22. Furthermore, the accumulation of Th17 cells in MPE predicted improved patient survival. These data provide the basis for developing immune-boosting strategies based on ridding the cancer patient of this cell population.


Assuntos
Diferenciação Celular/imunologia , Quimiotaxia de Leucócito/imunologia , Neoplasias Pulmonares/imunologia , Derrame Pleural Maligno/imunologia , Células Th17/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Separação Celular , Quimiocinas/análise , Quimiocinas/imunologia , Quimiocinas/metabolismo , Citocinas/análise , Citocinas/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imunofluorescência , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Derrame Pleural Maligno/citologia , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo
16.
Zhonghua Jie He He Hu Xi Za Zhi ; 31(12): 902-7, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19134406

RESUMO

OBJECTIVE: To explore the anti-tumor immune responses of dendritic cells (DCs) loaded with intact wild-type p53 to mice challenged with tumor cells expressing p53 genes with mutations at different sites. METHODS: Ad-p53-DC immunization function was assessed by the expression of surface molecules and allogeneic MLR. DCs derived from bone marrow were transduced with adenovirus or a human wild-type p53 containing recombinant adenovirus (Ad-DC and Ad-p53-DC) and immunized C57BL/6 mice. Splenocytes were separated and cell cytotoxicity was measured against tumor cells expressing mutant p53 (MethA, D459 and P815) in a standard 6-h(51)Cr-release assay. Effector and target cells were incubated in the presence of anti-CD(4) or anti-CD(8) antibody. Ad-p53-DC was immunized in control Ad-DC before or after mice were challenged with either D459 tumor or with MethA sarcoma cells to observe whether immune response would provide tumor protection. RESULTS: Immunization with Ad-p53-DC developed significantly higher substantial CTL responses against Ad-p53-P815, D459 and MethA cells (effectors: target cells = 50:1), (27.8 +/- 3.4)%, (23.5 +/- 2.7)%, (58.3 +/- 9.2)% than with Ad-DC (9.3 +/- 1.8)%, (4.6 +/- 1.0)%, (23.5 +/- 3.7)% (t(d) = 5.79, 3.68, 5.02, all P < 0.05). In Ad-p53-DC immunized mice, anti-CD(8) antibody blocked the cytotoxicity against Ad-p53-P815 (26.7 +/- 2.8)% or D459 (6.1 +/- 1.2)%, but not anti-CD(4) antibody [(59.8 +/- 4.6)%, (18.9 +/- 2.4)%, t(d) = 8.79 or 9.18, all P < 0.05]. Ad-p53-DC immunization provided complete tumor protection in 80% of mice challenged with D459 and in 70% of mice challenged with MethA, while none protected in Ad-DC immunization group (chi(2) = 6.72, 5.86, all P < 0.05). Treated with Ad-p53-DC after D459 inoculation subcutaneously, mice were killed due to the bulky tumor more than 2 weeks later than the mice in the Ad-DC treatment group during 7 week observation (chi(2) = 9.48, P < 0.05). CONCLUSION: DCs transfected with 100 MOI Ad-p53 induced intense CTL responses against P815, D459 and MethA. This CTL response is mediated by CD(8)(+) T cells. Treatment with Ad-p53-DC significantly developed tumor immunology and slowed the growth of established tumors.


Assuntos
Células Dendríticas/imunologia , Neoplasias Experimentais/terapia , Linfócitos T Citotóxicos/imunologia , Proteína Supressora de Tumor p53/genética , Adenoviridae/genética , Animais , Células da Medula Óssea , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Vetores Genéticos , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Transfecção
17.
Am J Chin Med ; 35(6): 1011-20, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18186587

RESUMO

Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-gamma in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-gamma and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.


Assuntos
Anti-Inflamatórios/farmacologia , Asma/metabolismo , Fator de Transcrição GATA3/metabolismo , Interferon gama/metabolismo , Interleucina-4/metabolismo , Pirazinas/farmacologia , Proteínas com Domínio T/metabolismo , Animais , Asma/induzido quimicamente , Asma/patologia , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Eosinófilos/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ovalbumina , Ratos , Células Th1/efeitos dos fármacos , Células Th1/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/metabolismo
18.
Artigo em Chinês | MEDLINE | ID: mdl-16188099

RESUMO

OBJECTIVE: To investigate the effect of AP-1 Decoy on matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1) imbalance induced by bleomycin-A5 (BLM-A5) in pulmonary fibroblasts. METHODS: Pulmonary fibroblasts were primary cultured, and transferred with AP-1 Decoy before treated with BLM-A5. MMPs activity in medium was determined by gelatin zymography. Protein content of TIMP-1 in medium was detected by ELISA. Expression of MMP-2 mRNA and TIMP-1 mRNA were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: BLM-A5 induced the increase in activity of MMP-2 at 12 h [A: (0.77 +/- 0.08) vs (0.65 +/- 0.07) P < 0.05], but it was suppressed by AP-1 Decoy [A: (0.68 +/- 0.05)]. BLM-A5 up-regulated the expression of protein and mRNA of TIMP-1 after 12 h, and 24 h [(39.3 +/- 4.3), (46.3 +/- 4.8) ng/ml vs (28.9 +/- 2.7), (31.6 +/- 2.4) ng/ml] and [Absorbance ratio to beta-actin: (0.94 +/- 0.13, 1.08 +/- 0.06) vs (0.76 +/- 0.07, 0.75 +/- 0.08)] (P < 0.05 or P < 0.01) but AP-1 Decoy modulated the up-regulation. All these indexes in AP-1 Decoy group had no significant difference in contrast to the normal group. Mutant AP-1 Decoy had not the same function as AP-1 Decoy on the expression of MMP-2 and TIMP-1 in pulmonary fibroblasts. CONCLUSION: AP-1 Decoy inhibits the increase in MMP-2 activity and the up-regulation of TIMP-1 induced by BLM-A5 in pulmonary fibroblasts.


Assuntos
Fibroblastos/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Transcrição AP-1/metabolismo , Bleomicina/análogos & derivados , Bleomicina/farmacologia , Fibroblastos/efeitos dos fármacos , Humanos , Pulmão/citologia , Pulmão/metabolismo , Fibrose Pulmonar/metabolismo
19.
Sheng Li Xue Bao ; 57(4): 493-7, 2005 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-16094498

RESUMO

To investigate the role of found in inflammatory zone 1 (FIZZ1) protein in the pathogenesis of experimental pulmonary fibrosis, 48 male Sprague-Dawley rats were randomly divided into two groups, the pulmonary fibrosis group and the control group. Rat pulmonary fibrosis was reproduced by an intratracheal injection of bleomycin (5 mg/kg body weight). Normal saline (1 ml/kg body weight) was given intratracheally injection in the control group. There were 24 rats in each group, and 6 animals were separately killed on the 7th, 14th, 21th and 28th day after treated with bleomycin or normal saline. Then the following tests were undertaken: (1) HE and Masson staining of lung section;(2) Determination of lung tissue hydroxyproline (HYP);(3) Immunohistochemical staining of protein of FIZZ1 in the lung;(4) In situ hybridization of FIZZ1 mRNA in the lung. The results showed: (1) There were full of inflammatory cells in the lung, the interval of alveoli enlarged and many alveolar spaces disappeared on the 7th day after treated with bleomycin in the fibrosis group. Collagen began to proliferate after 14 d. The pulmonary fibrosis was stably established on the 28th day, full of green fibers in the Masson staining of lung section. (2) The expression of FIZZ1 protein in the lung increased after 7 d in bleomycin-treated animals (3.013+/-0.326 vs 0.473+/-0.056, P<0.01 vs control), but was slightly decreased on the 14th day (2.124+/-0.197) and expensively decreased on the 21st day (1.760+/-0.105) and the 28th day (0.691+/-0.081). (3) The expression of FIZZ1 mRNA in the lung also increased after 7 d by treated with bleomycin (3.795+/-0.338 vs 0.678+/-0.087, P<0.01 vs control), but decreased on the 14th day (1.276+/-0.104) and further decreased on the 28th day (0.896+/-0.084). The expression of FIZZ1 protein and mRNA in fibrosis group was higher than that in the control group (P<0.05 or P<0.01). The results suggest that FIZZ1 protein and FIZZ1 mRNA are dynamically changed in the lung with experimental pulmonary fibrosis, which may contribute to the pathogenesis of pulmonary fibrosis.

20.
Zhonghua Yi Xue Za Zhi ; 83(13): 1169-72, 2003 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-12921638

RESUMO

OBJECTIVE: To explore the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the growth of human lung cancer cell lines and its possible mechanism. METHODS: Human non-small cell lung cancer (NSCLC) cells of the A549 line and human small cell lung cancer (SCLC) of the LTEP-P line were cultured and were divided into 3 groups respectively: control group, 15d-PGJ(2) group (15d-PGJ(2), a PPAR-gamma activator, was added), and ciglitazone group (ciglitazone, am antidiabetic drug, was added). Twenty-four, forty-eight, and seventy-two hours later, nested RT-PCR was used to detect t the expression of PPAR-gamma mRNA, Western blotting technique was used to detect the expression of PPAR-gamma protein, MTT staining was used to observe the proliferation of cells induced by PPAR-gamma agonists, TUNEL method was used to observe the apoptosis of cells affected by the ligands of PPAR-gamma, the expressions of bax, and bcl-2 mRN and proteins were examined by in situ hybridization and immunohistochemistry, and the expression of caspase-3 was detected by immunohistochemistry. RESULTS: PPAR-gamma was expressed in the two lung cancer cell lines. The cell proliferation was inhibited by 15d-PGJ(2) and ciglitazone, especially the former, in dose-dependent and time-dependent manners. The apoptosis rates were (1.9 +/- 0.5)%, (9.8 +/- 1.5)%, and (5.6 +/- 1.1)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a significant difference between ant 2 groups (all P < 0.05). The expression rate of bax were (9,2 +/- 1.5)%, (63 +/- 10)%, and (31 +/- 6)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a very significant difference between ant 2 groups (all P < 0.01). he expression rate of bcl-2 were (18 +/- 3)%, (36 +/- 9)%, and (33 +/- 7)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a very significant difference between the control group and any of the agonist-treated groups (all P < 0.01) and without significant difference between the two treated groups. The expression rates of caspase-3 were (6.5 +/- 1.0)%, (65 +/- 11)%, and (40 +/- 7)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a significant difference between any 2 group (all P < 0.01). The caspase-3 level was positively correlated with the level of apoptosis. CONCLUSION: Activated by ligands, PPAR-gamma remarkably inhibits the growth of human lung cancer cells through inducing apoptosis. Caspase-3 and bax/bcl-2 play a role in this process, PPAR-gamma is so important in the pathogenesis and/or progression of lung cancer that it may be a novel therapeutical target against lung cancer.


Assuntos
Apoptose , Prostaglandina D2/análogos & derivados , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3 , Caspases/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Prostaglandina D2/farmacologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/genética , Tiazolidinedionas/farmacologia , Fatores de Tempo , Fatores de Transcrição/agonistas , Fatores de Transcrição/genética , Proteína X Associada a bcl-2
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