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1.
Phytother Res ; 37(4): 1260-1273, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37041670

RESUMO

Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Luteína/metabolismo , Luteína/farmacologia , Luteína/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais
2.
BMC Genomics ; 22(1): 911, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930131

RESUMO

BACKGROUND: Known as the prerequisite component for the heterosis breeding system, the male sterile line determines the hybrid yield and seed purity. Therefore, a deep understanding of the mechanism and gene network that leads to male sterility is crucial. BS366, a temperature-sensitive genic male sterile (TGMS) line, is male sterile under cold conditions (12 °C with 12 h of daylight) but fertile under normal temperature (20 °C with 12 h of daylight). RESULTS: During meiosis, BS366 was defective in forming tetrads and dyads due to the abnormal cell plate. During pollen development, unusual vacuolated pollen that could not accumulate starch grains at the binucleate stage was also observed. Transcriptome analysis revealed that genes involved in the meiotic process, such as sister chromatid segregation and microtubule-based movement, were repressed, while genes involved in DNA and histone methylation were induced in BS366 under cold conditions. MethylRAD was used for reduced DNA methylation sequencing of BS366 spikes under both cold and control conditions. The differentially methylated sites (DMSs) located in the gene region were mainly involved in carbohydrate and fatty acid metabolism, lipid metabolism, and transport. Differentially expressed and methylated genes were mainly involved in cell division. CONCLUSIONS: These results indicated that the methylation of genes involved in carbon metabolism or fatty acid metabolism might contribute to male sterility in BS366 spikes, providing novel insight into the molecular mechanism of wheat male sterility.


Assuntos
Transcriptoma , Triticum , Metilação de DNA , Pólen/genética , Temperatura , Triticum/genética
3.
J Microbiol Immunol Infect ; 54(1): 54-60, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32359943

RESUMO

BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders. METHODS: We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China. RESULTS: Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significantly elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%). CONCLUSIONS: Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection.


Assuntos
COVID-19/epidemiologia , Infecção Hospitalar/epidemiologia , Hotspot de Doença , Pessoal de Saúde , Doenças Profissionais/epidemiologia , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/terapia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/terapia , Feminino , Humanos , Controle de Infecções , Transmissão de Doença Infecciosa do Paciente para o Profissional , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neurocirurgia , Doenças Profissionais/diagnóstico , Doenças Profissionais/terapia , Estudos Prospectivos , Centro Cirúrgico Hospitalar , Tomografia Computadorizada por Raios X
4.
Pharmacol Res ; 161: 105111, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33065284

RESUMO

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia , Ativação de Macrófagos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Macrófagos Associados a Tumor/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Plasticidade Celular , Humanos , Terapia de Alvo Molecular , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Fenótipo , Transdução de Sinais , Microambiente Tumoral , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
5.
Clin Gastroenterol Hepatol ; 18(8): 1753-1759.e2, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32311512

RESUMO

BACKGROUND & AIMS: We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. METHODS: We performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR. RESULTS: Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P < .05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P < .001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P = .010), during these patients' hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P = .039). CONCLUSIONS: At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.


Assuntos
Betacoronavirus/isolamento & purificação , Portador Sadio/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diarreia/epidemiologia , Diarreia/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Adulto , Idoso , Contagem de Células Sanguíneas , Análise Química do Sangue , COVID-19 , China , Diarreia/patologia , Fezes/virologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/virologia , Pandemias , Faringe/virologia , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
6.
Planta ; 247(6): 1307-1321, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29504038

RESUMO

MAIN CONCLUSION: Transcriptome analysis was carried out for wheat seedlings and spikes from hybrid Jingmai 8 and both inbred lines to unravel mechanisms underlying heterosis. Heterosis, known as one of the most successful strategies for increasing crop yield, has been widely exploited in plant breeding systems. Despite its great importance, the molecular mechanism underlying heterosis remains elusive. In the present study, RNA sequencing (RNA-seq) was performed on the seedling and spike tissues of the wheat (Triticum aestivum) hybrid Jingmai 8 (JM8) and its homozygous parents to unravel the underlying mechanisms of wheat heterosis. In total, 1686 and 2334 genes were identified as differentially expressed genes (DEGs) between the hybrid and the two inbred lines in seedling and spike tissues, respectively. Gene Ontology analysis revealed that DEGs from seedling tissues were significantly enriched in processes involved in photosynthesis and carbon fixation, and the majority of these DEGs expressed at a higher level in JM8 compared to both inbred lines. In addition, cell wall biogenesis and protein biosynthesis-related pathways were also significantly represented. These results confirmed that a combination of different pathways could contribute to heterosis. The DEGs between the hybrid and the two inbred progenitors from the spike tissues were significantly enriched in biological processes related to transcription, RNA biosynthesis and molecular function categories related to transcription factor activities. Furthermore, transcription factors such as NAC, ERF, and TIF-IIA were highly expressed in the hybrid JM8. These results may provide valuable insights into the molecular mechanisms underlying wheat heterosis.


Assuntos
Regulação da Expressão Gênica de Plantas , Vigor Híbrido/genética , Transcriptoma , Triticum/genética , Perfilação da Expressão Gênica , Ontologia Genética , Endogamia , Inflorescência/genética , Inflorescência/fisiologia , Fotossíntese , Plântula/genética , Plântula/fisiologia , Análise de Sequência de RNA , Triticum/fisiologia
7.
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.

8.
Am J Respir Cell Mol Biol ; 56(3): 342-352, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27767332

RESUMO

Toll-like receptor (TLR) 2 has a well-known role in sensing multiple ligands that include microbial products, endotoxin, and some extracellular matrix molecules; however, its role in the development of malignant pleural effusion (MPE) remains unknown. We performed the present study to explore the impact of TLR2 signaling on the development of MPE and to define the underlying mechanisms by which TLR2 works. Development of MPE was compared between TLR2-/- and wild-type (WT) mice. The effect of TLR2 on differentiation of T helper type 17 (Th17), Th9, and Th2 cells in MPE was explored. The mechanisms of TLR2 on survival of mice bearing MPE were also investigated. MPE volume in TLR2-/- mice was lower than that in WT mice, and the survival of TLR2-/- mice bearing MPE was longer than that of WT mice. TLR2 deficiency increased, and TLR2 activation decreased, Th17 cells in MPE, whereas TLR2 signaling showed the contrary effects on Th2 cells. Th9 cells were increased in MPE of TLR2-/- mice but were not influenced by TLR2 signaling. Intraperitoneal injection of anti-IL-17 monoclonal antibody (mAb), anti-IL-9 mAb, or recombinant mouse IL-4 accelerated the death of TLR2-/- mice bearing MPE, and intraperitoneal injection anti-IL-17 mAb in TLR2-/- mice was associated with a significantly shorter survival time than in WT mice. We have demonstrated, for the first time, that TLR2 signaling promotes the development of MPE and accelerates the death of mice bearing MPE by directly suppressing Th17 cell differentiation and directly promoting Th2 cell differentiation, and also by indirectly suppressing Th9 cell differentiation via an IL-17-dependent mechanism.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Derrame Pleural Maligno/imunologia , Receptor 2 Toll-Like/metabolismo , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-17/farmacologia , Camundongos Endogâmicos C57BL , Derrame Pleural Maligno/patologia , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Receptor 2 Toll-Like/agonistas
10.
Respir Care ; 59(10): 1542-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24962223

RESUMO

BACKGROUND: Adrenomedullin (ADM) is a regulatory peptide with many biological actions, but little is known about its role in patients with COPD exacerbation. The purpose of this study was to evaluate the diagnostic and prognostic value of plasma ADM levels on hospital admission in patients with COPD exacerbation. METHODS: Consecutive subjects admitted to the hospital for COPD exacerbation were included and were followed up for 1 y; in addition, subjects with stable COPD from an out-patient clinic and healthy volunteers were recruited as controls. RESULTS: Compared with healthy subjects (145 pg/mL [interquartile range {IQR} 103-290 pg/mL]), plasma ADM levels were significantly higher in subjects with COPD exacerbation (270 pg/mL [IQR 170-510 pg/mL], P = .001) and in subjects with stable COPD (400 pg/mL [IQR 210-525 pg/mL], P < .001). In subjects with COPD exacerbation, ADM levels were significantly elevated during exacerbation (560 pg/mL [IQR 495-630 pg/mL]) compared with the recovery phase (470 pg/mL [IQR 393-553 pg/mL], P = .01) and the stable phase (200 pg/mL [IQR 143-308 pg/mL], P < .001). In receiver operating characteristic analysis, in subjects with COPD exacerbation, ADM had high diagnostic accuracy in differentiating between exacerbation and the stable phase (area under the curve 0.97, 95% CI 0.93-1.02, P < .001). In Cox regression analysis, plasma ADM was not independently associated with 1-y survival (P = .97), but it could accurately predicted the need for ICU care (hazard ratio 1.37, 95% CI 1.09-1.72, P = .008). CONCLUSIONS: Plasma ADM is a valuable biomarker to confirm COPD exacerbation; furthermore, plasma ADM independently predicts the need of ICU care, although it is not associated with long-term mortality in patients with COPD exacerbation.


Assuntos
Adrenomedulina/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
11.
Oncol Lett ; 8(1): 449-453, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24959294

RESUMO

Tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs) are difficult to differentiate between in certain clinical situations. Interleukin (IL)-33 is a cytokine that participates in inflammatory responses and may have a role in pleural effusions. The present study aimed to investigate the concentrations and potential differential significance of IL-33 in patients with TPE and MPE. IL-33 levels in pleural effusion and serum samples were detected using sandwich enzyme-linked immunosorbent assay in 23 patients with TPE and 21 patients with MPE. The concentration of IL-33 (mean ± standard deviation) in the TPE patients (22.962±0.976 ng/l) was significantly higher than that in the MPE patients (12.603±5.153 ng/l; P<0.001; z=-4.572); however, there was no significant difference in the serum level of IL-33 in the patients with TPE compared with those with MPE (P>0.05). The concentration of IL-33 in the pleural effusions was positively correlated with that in the serum samples in each group (TPE: r=0.563, P=0.05; MPE: r=0.535, P<0.05). The cut-off value of pleural IL-33 for TPE was 19.86 ng/l, which yielded a sensitivity of 0.869, a specificity of 0.905 and an area under the corresponding receiver operating characteristic curve of 0.903. The present study identified that the level of pleural IL-33 is significantly increased in TPEs and may serve as a novel biomarker to differentiate between patients with TPE and MPE.

12.
J Huazhong Univ Sci Technolog Med Sci ; 33(1): 27-32, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23392703

RESUMO

Both T helper IL-17-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in malignant pleural effusion (MPE). However, the possible imbalance between Th17 cells and Tregs, as well as the association of Th17/Treg and Th1/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as Th1/Th2 balance in MPE. The number of Th17, Tregs, Th1, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Th17, Tregs, Th1, and Th2 cells was explored. It was found that the number of Th17, Tregs, Th1, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Th17 cells was correlated negatively with Tregs in MPE, but not in blood. Th17 cells and Th17/Treg ratio were positively, and Tregs were negatively, correlated with Th1 cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Th17 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Th17/Treg imbalance exists in MPE.


Assuntos
Derrame Pleural Maligno/imunologia , Derrame Pleural Maligno/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Ying Yong Sheng Tai Xue Bao ; 24(8): 2197-204, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-24380338

RESUMO

Taking two winter wheat cultivars Ji' nan 17 and Shannong 8355 as test materials, this paper measured the superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and the malondialdehyde (MDA) and soluble protein contents in the functional leaves and sheaths of the tillers at different positions at stem elongation stage under low temperature stress, and then, the freezing resistance of the tillers was comprehensively evaluated by the methods of principal component analysis and cluster analysis. The results showed that under low temperature stress, the SOD, POD, and CAT activities in the functional leaves and sheaths of each tiller at stem elongation stage increased, but the MDA and soluble protein contents increased or decreased to some extent. By using principal component analysis and cluster analysis, the tillers of each cultivar were grouped into three kinds of freezing resistance type. For Ji' nan 17, the main stem, tiller I, and tiller II belonged to high freezing resistance type, the tiller III, tiller IV, and tiller I p belonged to medium freezing resistance type, and the tiller II p belonged to low freezing resistance type. For Shannong 8355, the main stem, tiller I, tiller II, and tiller III belonged to high freezing resistance type, the tiller IV and tiller I p belonged to medium freezing resistance type, and the tiller II p belonged to low freezing resistance type. It was concluded that the freezing resistance of the winter wheat tillers at different positions at stem elongation stage differed, with the lower position tillers being more resistant than the higher position tillers.


Assuntos
Adaptação Fisiológica/fisiologia , Agricultura/métodos , Temperatura Baixa , Triticum/fisiologia , China , Ecossistema , Folhas de Planta/metabolismo , Caules de Planta/metabolismo , Caules de Planta/fisiologia , Estações do Ano , Estresse Fisiológico/fisiologia , Superóxido Dismutase/metabolismo , Triticum/metabolismo
14.
Am J Respir Crit Care Med ; 186(11): 1168-79, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23065014

RESUMO

RATIONALE: IL-9-producing CD4(+) T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated. OBJECTIVES: To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells. METHODS: Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated. MEASUREMENTS AND MAIN RESULTS: The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers. CONCLUSIONS: Our data revealed that Th9 cells were increased in MPE and that Th9 cells exerted an important immune regulation on lung cancer cells in human tumor environment.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Neoplasias Pulmonares/imunologia , Derrame Pleural Maligno/imunologia , Células Th1/imunologia , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-17/imunologia , Interleucina-17/metabolismo , Interleucina-9/imunologia , Interleucina-9/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/citologia , Derrame Pleural Maligno/patologia , Prognóstico , Sensibilidade e Especificidade , Transdução de Sinais , Células Th1/metabolismo , Células Tumorais Cultivadas
15.
Cancer Lett ; 326(1): 23-32, 2012 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-22809567

RESUMO

Th22 cells have been reported to be involved in human cancers. However, differentiation and immune regulation of Th22 cells in malignant pleural effusion (MPE) remain unknown. We noted that Th22 cell numbers were increased in MPE, and that IL-22 substantially promoted the proliferation and migratory activity of A549 cells. Moreover, IL-22 could strongly facilitate intercellular adhesion of A549 cells to pleural mesothelial cell monolayers. Our data revealed that the increase in Th22 cells in MPE was due to pleural cytokines and chemokines, and that Th22 exerted an important immune regulation on cancer cells in human pleural malignant environment.


Assuntos
Interleucinas/metabolismo , Neoplasias Pulmonares/imunologia , Derrame Pleural Maligno/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto , Animais , Adesão Celular , Diferenciação Celular , Linhagem Celular Tumoral , Quimiotaxia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Interleucina 22
16.
PLoS One ; 7(7): e40450, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22792330

RESUMO

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.


Assuntos
Interleucinas/metabolismo , Neoplasias Pulmonares/diagnóstico , Linfócitos/metabolismo , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Células Cultivadas , Diagnóstico Diferencial , Exsudatos e Transudatos/metabolismo , Feminino , Humanos , Interleucinas/sangue , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural/metabolismo , Derrame Pleural/patologia , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Curva ROC , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/patologia , Adulto Jovem
17.
PLoS One ; 7(4): e35629, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22539986

RESUMO

Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor which has been used in conjunction with other anti-cancer agents in the treatment of patients with many cancers. It remains controversial whether bevacizumab can prolong survival in cancer patients. This meta-analysis was therefore performed to evaluate effect of bevacizumab on survival in cancer patients. PubMed, EMBASE, and Web of Science databases were searched for English-language studies of randomized controlled trials comparing bevacizumab with control therapy published through February 8, 2012. Progression-free survival, overall survival, and one-year survival rate were analyzed using random- or fixed-effects model. Thirty one assessable randomized controlled trials were identified. A significant improvement in progression-free survival in cancer patients was attributable to bevacizumab compared with control therapy (hazard ratio, 0.72; 95% confidence interval, 0.68 to 0.76; p<0.001). Overall survival was also significantly longer in patients were treated with bevacizumab (hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.91; p<0.001). The significant benefit in one-year survival rate was further seen in cancer patients receiving bevacizumab (odds ratio, 1.30; 95% confidence interval, 1.20 to 1.41; p<0.001). Current evidences showed that bevacizumab prolong progression-free survival and overall survival, and increase one-year survival rate in cancer patients as compared with control therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias/mortalidade , Bevacizumab , Bases de Dados Factuais , Humanos , Neoplasias/tratamento farmacológico , Razão de Chances , Modelos de Riscos Proporcionais , Taxa de Sobrevida
18.
PLoS One ; 7(2): e31710, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22363712

RESUMO

Newly discovered IL-9-producing CD4(+) helper T cells (Th9 cells) have been reported to contribute to tissue inflammation and immune responses, however, differentiation and immune regulation of Th9 cells in tuberculosis remain unknown. In the present study, our data showed that increased Th9 cells with the phenotype of effector memory cells were found to be in tuberculous pleural effusion as compared with blood. TGF-ß was essential for Th9 cell differentiation from naïve CD4(+) T cells stimulated with PMA and ionomycin in vitro for 5 h, and addition of IL-1ß, IL-4 or IL-6 further augmented Th9 cell differentiation. Tuberculous pleural effusion and supernatants of cultured pleural mesothelial cells were chemotactic for Th9 cells, and this activity was partly blocked by anti-CCL20 antibody. IL-9 promoted the pleural mesothelial cell repairing and inhibited IFN-γ-induced pleural mesothelial cell apoptosis. Moreover, pleural mesothelial cells promoted Th9 cell differentiation by presenting antigen. Collectively, these data provide new information concerning Th9 cells, in particular the collaborative immune regulation between Th9 cells and pleural mesothelial cells in human M. tuberculosis infection. In particular, pleural mesothelial cells were able to function as antigen-presenting cells to stimulate Th9 cell differentiation.


Assuntos
Diferenciação Celular , Células Epiteliais/imunologia , Interleucina-9/imunologia , Ativação Linfocitária/imunologia , Pleura/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Tuberculose/imunologia , Adulto , Apresentação de Antígeno/efeitos dos fármacos , Apresentação de Antígeno/imunologia , Antígenos de Bactérias/imunologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Quimiocina CCL20/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Humanos , Interferon gama/farmacologia , Interleucina-4/farmacologia , Ionomicina/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/fisiologia , Fenótipo , Derrame Pleural/imunologia , Derrame Pleural/microbiologia , Derrame Pleural/patologia , Receptores de Quimiocinas/metabolismo , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Tuberculose/microbiologia , Tuberculose/patologia , Cicatrização/efeitos dos fármacos , Adulto Jovem
19.
Am J Respir Crit Care Med ; 185(6): 660-9, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22199006

RESUMO

RATIONALE: IL-22-producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown. OBJECTIVES: To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space. METHODS: The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed. MEASUREMENTS AND MAIN RESULTS: Th22 cells were significantly higher in TPE than in blood. IL-1ß, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4(+) T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen. CONCLUSIONS: The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation.


Assuntos
Imunidade Celular , Interleucinas/biossíntese , Ativação Linfocitária/imunologia , Pleura/patologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Tuberculose Pleural/imunologia , Células Apresentadoras de Antígenos/metabolismo , Diferenciação Celular , Epitélio/imunologia , Epitélio/metabolismo , Epitélio/patologia , Humanos , Pleura/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Tuberculose Pleural/patologia , Interleucina 22
20.
Huan Jing Ke Xue ; 31(3): 821-7, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20358849

RESUMO

A bacterial strain, able to efficiently degrade benzene, toluene, ethyl benzene, and o-xylene ( BTEX) compounds, was isolated by acclimating and enriching the activated sludge from the aeration tank in refinery wastewater treatment plant using BTEX as the sole carbon source. Based on the morphological characteristics, physiological and biochemical characteristics, sequence analysis of 16S rDNA,and Biolog identification system,the isolate was identified as Mycobacterium cosmeticum which was a newly discovered species able to degrade BTEX. The optimal conditions for the growth of the strain were at 30 degrees C and pH 7.0. The order of BTEX degradation by this isolate is benzene,toluene, ethyl benzene,and o-xylene. The specific oxygen utilization rates (SOUR) of the strain degrading benzene,toluene, ethyl benzene, and o-xylene were 165.3, 170.5, 49.3 and 57.4 mg x (min x mg)(-1), respectively. The degrading process of the strain followed the Haldane kinetic model. The maximum specific degradation rate degrading benzene, toluene, ethyl benzene,and o-xylene were 0.518, 0.491, 0.443 and 0.422 h(-1), respectively. Accordingly,the maximum specific growth rate 0.352, 0.278, 0.172 and 0.136 h(-1), respectively.


Assuntos
Derivados de Benzeno/isolamento & purificação , Benzeno/isolamento & purificação , Poluentes Ambientais/isolamento & purificação , Mycobacterium/isolamento & purificação , Tolueno/isolamento & purificação , Benzeno/metabolismo , Derivados de Benzeno/metabolismo , Biodegradação Ambiental , Poluentes Ambientais/metabolismo , Mycobacterium/classificação , Mycobacterium/metabolismo , Tolueno/metabolismo , Xilenos/isolamento & purificação , Xilenos/metabolismo
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