Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 70
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Aging (Albany NY) ; 12(2): 1186-1200, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958320

RESUMO

Exposure to particulate matter (PM) is associated with increased incidence of respiratory diseases. The present study aimed to investigate the roles of fibroblast growth factor 10 (FGF10) in PM-induced lung injury. Mice were intratracheally instilled with FGF10 or phosphate-buffered saline at one hour before instillation of PM for two consecutive days. In addition, the anti-inflammatory impact of FGF10 in vitro and its effect on the high-mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4) pathway was investigated. It was found that PM exposure is associated with increased inflammatory cell infiltration into the lung and increased vascular protein leakage, while FGF10 pretreatment attenuated both of these effects. FGF10 also decreased the PM-induced expression of interleukin (IL)-6, IL-8, tumor necrosis factor-α and HMGB1 in murine bronchoalveolar lavage fluid and in the supernatants of human bronchial epithelial cells exposed to PM. FGF10 exerted anti-inflammatory and cytoprotective effects by inhibiting the HMGB1-TLR4 pathway. These results indicate that FGF10 may have therapeutic values for PM-induced lung injury.

2.
World J Clin Cases ; 7(22): 3832-3837, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31799311

RESUMO

BACKGROUND: Hilar masses with stenosis of the bronchus occur mainly due to malignant diseases, such as lung cancer. Hilar masses resulting from invasive aspergillosis are extremely rare and occur mostly in severely immunosuppressed patients. CASE SUMMARY: In the current case report, we have documented a unique case of invasive aspergillosis presenting as a mass in the hilum and bronchial stenosis under bronchoscopy mimicking lung cancer in a 54-year-old man with diabetes mellitus. The histological analysis of bronchial membrane biopsy demonstrated fungal elements of 45° branching hyphae with positive Periodic Acid-Schiff and Grocott staining. After 3 mo of antifungal therapy, the symptoms, computed tomography scan and bronchoscopy manifestations all showed improvement. CONCLUSION: We highlight that clinicians should consider a diagnosis of invasive aspergillosis when radiological examination shows pseudotumor appearance in diabetes mellitus patients.

3.
Am J Transl Res ; 11(11): 6977-6988, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814901

RESUMO

Chronic respiratory disorders are some of the most frequent and severe chronic diseases in China. Epidemiological research has shown that particulate matter (PM) is a risk factor and is closely correlated to the progression of numerous respiratory diseases. Fibroblast growth factor 10 (FGF10) is a mesenchymal-epithelial signaling messenger essential for the development and environmental stability of several tissues. Nevertheless, its role in PM-induced airway inflammation remains unclear. The present study aimed to explore the mechanisms underlying the FGF10-related slowing of lung injury and inflammation in vivo and in vitro, as well as the therapeutic potential of these phenomena. Mice were intraperitoneally injected with a vehicle (PBS) or FGF10 (0.5 mg/kg) at one hour before intratracheal treatment with vehicle (PBS) or PM (4 mg/kg) for two consecutive days. Human airway epithelial BEAS-2B cells were exposed to a vehicle (PBS) or FGF10 (10 ng/ml) in vitro at one hour prior to incubation with a vehicle or PM (200 ug/ml) for 24 hours. Then, the impact on inflammatory molecules was investigated. In vivo, it was found that FGF10 diminished the inflammatory cell aggregation and reduced the apoptosis. Interestingly, in the PM group, the level of FGF10 increased in the bronchoalveolar lavage fluid (BALF). However, the pre-treatment with FGF10 markedly impaired the PM-induced increase in IL-6, IL-8, TNF-α and PGE2 levels in BALF and the cell supernatant. In conclusion, the present findings indicate that FGF10 attenuates PM-induced airway inflammation by inhibiting apoptosis and inflammation. This may be exploited for the prevention and management of PM-induced airway inflammation.

4.
Cell Biol Toxicol ; 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31884678

RESUMO

Particulate matter (PM) is an environmental pollutant closely associated with human airway inflammation. However, the molecular mechanisms of PM-related airway inflammation remains to be fully elucidated. It is known that COX-2/PGE2 play key roles in the pathogenesis of airway inflammation. Filaggrin is a transmembrane protein contributing to tight junction barrier function. As such, Filaggrin prevents leakage of transported solutes and is therefore necessary for the maintenance of epithelial integrity. The objective of the present study was to investigate the regulatory mechanisms of COX-2/PGE2 and Filaggrin upon PM exposure both in vivo and in vitro. C57BL/6 mice received intratracheal instillation of PM for two consecutive days. In parallel, human bronchial epithelial cells (HBECs) were exposed to PM for 24 h. PM exposure resulted in airway inflammation together with upregulation of COX-2/PGE2 and downregulation of Filaggrin in mouse lungs. Corresponding dysregulation of COX-2/PGE2 and Filaggrin was also observed in HBECs subjected to PM. PM exposure led to the phosphorylation of ERK, JNK, and PI3K signaling pathways in a time-dependent manner, while blockade of PI3K with the specific molecular inhibitor LY294002 partially reversed the dysregulation of COX-2/PGE2 and Filaggrin. Moreover, pretreatment of HBECs with NS398, a specific molecular inhibitor of COX-2, and AH6809, a downstream PGE2 receptor inhibitor, reversed the downregulation of Filaggrin upon PM exposure. Taken together, these data demonstrated that the PI3K signaling pathway upregulated COX-2 as well as PGE2 and acted as a pivotal mediator in the downregulation of Filaggrin.

5.
Front Med ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741137

RESUMO

Regeneration carries the idea of regrowing partially or completely a missing organ. Repair, on the other hand, allows restoring the function of an existing but failing organ. The recognition that human lungs can both repair and regenerate is quite novel, the concept has not been widely used to treat patients. We present evidence that the human adult lung does repair and regenerate and introduce different ways to harness this power. Various types of lung stem cells are capable of proliferating and differentiating upon injury driving the repair/regeneration process. Injury models, primarily in mice, combined with lineage tracing studies, have allowed the identification of these important cells. Some of these cells, such as basal cells, broncho-alveolar stem cells, and alveolar type 2 cells, rely on fibroblast growth factor (FGF) signaling for their survival, proliferation and/or differentiation. While preclinical studies have shown the therapeutic benefits of FGFs, a recent clinical trial for acute respiratory distress syndrome (ARDS) using intravenous injection of FGF7 did not report the expected beneficial effects. We discuss the potential reasons for these negative results and propose the rationale for new approaches for future clinical trials, such as delivery of FGFs to the damaged lungs through efficient inhalation systems, which may be more promising than systemic exposure to FGFs. While this change in the administration route presents a challenge, the therapeutic promises displayed by FGFs are worth the effort.

6.
Int J Chron Obstruct Pulmon Dis ; 14: 2319-2329, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632001

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is recognized as a chronic lung disease with incomplete reversible airflow limitation, but its pathophysiology was still not clear. This study aimed at investigating regulatory roles of special miRNA-mRNA axis in COPD development. Methods: Differentially expressed miRNAs and downstream mRNAs were screened from the Gene Expression Omnibus (GEO) dataset by using the LIMMA package in R software. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct a co-expression network for COPD. The correlation of dysregulated miRNA(s) and COPD was analyzed, and miRNAs with significant differences were validated in peripheral blood mononuclear cells (PBMCs) from COPD patients by real-time PCR. Regulatory roles of candidate miRNAs and targeted mRNAs were investigated in vitro study. Results: Thirteen modules of co-expressed miRNAs and mRNAs were constructed from a selected cohort with WGCNA. Turquoise module with 12 differentially expressed miRNAs and 120 mRNAs was significantly correlated with COPD. The expression of hsa-miR-664a-3p, an upregulated miRNA in the module, was increased both in lung tissue and PBMCs from COPD patients, whereas that targeted four and a half LIM domains 1 (FHL1) gene was decreased and positively correlated with forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC%) (r = 0.59, p < 0.01). In vitro, luciferase activity assay revealed FHL1 as a target of hsa-miR-664a-3p and it could be directly downregulated by overexpression of hsa-miR-664a-3p. Furthermore, cigarette smoke extract could increase hsa-miR-664a-3p level and decrease FHL1 level in Beas-2B cells. Conclusion: The present study validated significant upregulation of hsa-miR-664a-3p in COPD patients, and its target gene FHL1 was downregulated and positively correlated with FEV1/FVC%; both hsa-miR-664a-3p and FHL1 could be regulated by cigarette smoke extract. Results of bioinformatic analyses and expanded validation suggest that the axis from hsa-miR-664a-3p to FHL1 might play a key role in cigarette smoke-induced COPD, and the exact mechanism should be confirmed in further studies.

7.
Mol Med Rep ; 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545412

RESUMO

Lipopolysaccharide (LPS) induces stress inflammation and apoptosis. Pulmonary epithelial cell apoptosis, which accelerates the progression of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), is the leading cause of mortality in patients with ALI/ARDS. The nephroblastoma overexpressed protein (CCN3), an inflammatory modulator, is reported to be a biomarker in ALI. Using the LPS-induced ALI model, this study investigated the expression of CCN3 and its possible molecular mechanism in lung alveolar epithelial cell inflammation and apoptosis. Our data revealed that LPS treatment greatly increased the level of CCN3 in A549 cells. The A549 cells were transfected with specific CCN3 small interfering RNA (siRNA) using transfection reagent. CCN3 siRNA not only largely attenuated the expressions of the inflammatory cytokines interleukin (IL)-1ß and transforming growth factor (TGF)-ß1, but also reduced the apoptotic rate of the AEC II cells and affected the expressions of the apoptosis-associated proteins (Bcl-2 and caspase-3). Furthermore, CCN3 knockdown greatly inhibited the activation of nuclear factor-κB p65 in A549 cells. In addition, TGF-ß/p-Smad inhibitor (TP0427736) and NF-κB inhibitor (PDTC) significantly attenuated the expression level of CCN3 in A549 cells. In conclusion, our data indicated that CCN3 siRNA affected downstream signal through TGF-ß/ p-Smad or NF-κB pathway, leading to the inhibition of cell inflammation and apoptosis in human alveolar epithelial cells.

8.
Aging (Albany NY) ; 11(18): 7805-7816, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31553308

RESUMO

We explored the effects of compound 33, a synthetic chalcone derivative with antioxidant activity, on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compound 33, dexamethasone or vehicle was administered intragastrically to mice 6 h before intratracheal instillation of LPS. After 24 h, the effects of compound 33 on alveolar structural damage were evaluated by assessing lung morphology and the wet/dry weight ratio. Protein and proinflammatory cytokine levels and superoxide dismutase activity were also examined in the cell free supernatant of bronchoalveolar lavage fluid. Additionally, we investigated the anti-inflammatory and antioxidant activity of compound 33 in vitro and its effects on the MAPK/NF-κB and Nrf2/HO-1 pathways. Pretreatment with compound 33 prevented LPS-induced structural damage, tissue edema, protein exudation, and overproduction of proinflammatory mediators. The effects of compound 33 were similar to or greater in magnitude than those of the positive control, dexamethasone. Moreover, compound 33 exerted anti-inflammatory and antioxidant effects in vitro by inhibiting the MAPK/NF-κB pathway and activating the Nrf2/HO-1 pathway. Compound 33 may therefore be a promising candidate treatment for ALI.

9.
Transl Lung Cancer Res ; 8(2): 135-143, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31106124

RESUMO

Background: Previous studies have shown that there are different methods used to detect the epidermal growth factor receptor (EGFR) mutation status in plasma cell-free DNA (cfDNA) for advanced lung adenocarcinoma patients including the ADx-Amplification Refractory Mutation System (ADx-ARMS). We explored the performance of the ADx-ARMS in detecting the EGFR mutations in cfDNA. Methods: This prospective cohort study enrolled patients who presented with advanced (stage IIIb/IV) lung adenocarcinoma. EGFR mutations in plasma cfDNA and tumor tissues by ADx-ARMS were detected. Next-generation sequencing (NGS) in plasma was performed in patients with inconsistent gene region mutations in the plasma and matched tissue samples. We calculated the clinical parameters of the ADx-ARMS for EGFR mutation status in the plasma of cfDNA, using the tumor tissues as the standard for measurement. The objective response rate (ORR) and progression-free survival (PFS) were also calculated for patients receiving first-generation EGFR-tyrosine kinase inhibitors (TKIs) therapy. Results: In total, 203 patients were included in the final analysis. Mutations were discovered in 58.6% (119/203) of the tumor tissues and 31.0% (63/203) were detected EGFR mutations in both tumor tissues and matched plasma. The sensitivity and the specificity setting for detecting the EGFR mutations in the plasma using the ADx-ARMS were configured to 52.9% and 98.8%. An ORR of 64.8% was observed among the 71 patients who were identified as being EGFR-positive in their tumor tissues, who had received treatments using Gefitinib or Icotinib. Next, the ORR was observed to be 69.0% among the 42 patients with an EGFR mutation in their plasma. The median PFS of the patients with an EGFR mutation in tumor tissues and plasma were 10.0 vs. 11.0 months (P=0.175). The median PFS of the patients with an EGFR wild-type in the plasma was 8.7 months, which was significantly shorter than the EGFR mutant-type in plasma (P=0.001). Conclusions: Using ADx-ARMS as an approach with high specificity but moderate sensitivity to detect the EGFR mutations in plasma cfDNA and EGFR mutation status in plasma cfDNA using the ADx-ARMS can predict the tumor response for EGFR-TKIs.

10.
Biochim Biophys Acta Gen Subj ; 1863(6): 1079-1087, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954526

RESUMO

The endothelial cell (EC) barrier disruption has been implicated in vascular leakage and pulmonary edema. Many reports have shown that the EC barrier dysfunction is regulated by the sphingosine-1-phophate (S1P)/S1P receptor-1 (S1PR1) axis. Identifying downstream effectors for the S1P/S1PR1 axis in pulmonary vasculature has been limited by mixed populations in vitro cultures that do not retain physiological EC phenotype and complex of tedious proteomics. In this study, we used a combination of in vivo biotinylation and liquid chromatograph tandem mass spectrometry on three mouse models of S1pr1 expression, namely normal, knockout (KO) and high, to identify EC membrane proteins whose cell-surface expression is S1pr1-dependent. EC-specific KO of S1pr1 caused severe pulmonary vascular disruption and reduction of many membrane proteins on ECs. Using the MaxQuant software we were able to identify novel membrane targets of S1pr1, for instance, Cd105 and Plvap, by comparison with their membrane expressions among the three EC model systems. Moreover, regulation of Cd105 and Plvap by S1pr1 were validated with Western blot and immunostaining in vivo and in vitro. Our data suggest that S1pr1 dictates cell-surface localization of several apical membrane proteins in ECs. Our results are insightful for development of novel therapeutics to specifically target EC barrier function.


Assuntos
Membrana Celular/metabolismo , Endoglina/metabolismo , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Modelos Biológicos , /metabolismo , Animais , Linhagem Celular , Membrana Celular/genética , Endoglina/genética , Células Endoteliais/citologia , Camundongos , Camundongos Knockout , /genética
11.
Am J Emerg Med ; 37(6): 1215.e1-1215.e4, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31023584

RESUMO

Pleural trichomonosis is clinically rare, and very few cases of trichomonal empyema have been reported so far. A rare case of an 81-year-old woman with pyopeumothorax presenting with recurrent fever and macroscopic pyuria was present. Microscopic examination of the pleural effusion showed mobile flagellated protozoa which molecular methods identified as Tetratrichomonas. In addition, Streptococcus anginosus was discovered in pleural fluid cultures. Treatment with imipenem/cilastatin and metronidazole successfully eliminated the pathogens and led to relief of clinical symptoms. In the context of a review of the relevant literature, the clinical application of molecular methods in the diagnosis of pleural trichomonosis is underlined.


Assuntos
Empiema Pleural/parasitologia , Derrame Pleural/parasitologia , Pneumotórax/parasitologia , Trichomonadida/isolamento & purificação , Tricomoníase/diagnóstico , Idoso de 80 Anos ou mais , Antiprotozoários/uso terapêutico , Cilastatina/uso terapêutico , Empiema Pleural/diagnóstico , Empiema Pleural/microbiologia , Feminino , Humanos , Imipenem/uso terapêutico , Metronidazol/uso terapêutico , Derrame Pleural/microbiologia , Pneumotórax/diagnóstico , Pneumotórax/microbiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus anginosus/isolamento & purificação , Tricomoníase/tratamento farmacológico
12.
Cell Mol Life Sci ; 76(14): 2817-2832, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30887098

RESUMO

The respiratory epithelium arises from alveolar epithelial progenitors which differentiate into alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. AT2 cells are stem cells in the lung critical for the repair process after injury. Mechanisms regulating AT1 and AT2 cell maturation are poorly defined. We report that the activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased AT2 marker Sftpc and decreased miR-142 expression. Using miR-142 KO mice, we demonstrate an increase in the AT2/AT1 cell number ratio. Overexpression of miR-142 in alveolar progenitor cells in vivo led to the opposite effect. Examination of the KO lungs at E18.5 revealed enhanced expression of miR-142 targets Apc, Ep300 and Kras associated with increased ß-catenin and p-Erk signaling. Silencing of miR-142 expression in lung explants grown in vitro triggers enhanced Sftpc expression as well as increased AT2/AT1 cell number ratio. Pharmacological inhibition of Ep300-ß-catenin but not Erk in vitro prevented the increase in Sftpc expression triggered by loss of miR-142. These results suggest that the glucocorticoid-miR-142-Ep300-ß-catenin signaling axis controls pneumocyte maturation.


Assuntos
Células Epiteliais Alveolares/citologia , Linhagem da Célula , Pulmão/crescimento & desenvolvimento , MicroRNAs/genética , Organogênese , Mucosa Respiratória/citologia , Células Epiteliais Alveolares/metabolismo , Animais , Células Cultivadas , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Mucosa Respiratória/fisiologia
13.
Front Genet ; 10: 178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30923534

RESUMO

Members of the PEA3 transcription factors are emerging as bone fide targets for fibroblast growth factor (FGF) signaling. Among them, ETV4 and ETV5 appear to mediate FGF10 signaling during early embryonic lung development. In this paper, recently obtained Tg(Etv4-GFP) and Etv5 CreERT2-RFP fluorescent reporter lines were generally characterized during early embryonic development and in the context of FGF10 signaling, in particular. We found that both Tg(Etv4-GFP) and Etv5 CreERT2-RFP were primarily expressed in the epithelium of the lung during embryonic development. However, the expression of Etv5 CreERT2-RFP was much higher than that of Tg(Etv4-GFP), and continued to increase during development, whereas Tg(Etv4-GFP) decreased. The expression patterns of the surrogate fluorescent protein GFP and RFP for ETV4 and ETV5, respectively, agreed with known regions of FGF10 signaling in various developing organs, including the lung, where ETV4-GFP was seen primarily in the distal epithelium and to a lesser extent in the surrounding mesenchyme. As expected, ETV5-RFP was restricted to the lung epithelium, showing a decreasing expression pattern from distal buds to proximal conducting airways. FGF10 inhibition experiments confirmed that both Etv4 and Etv5 are downstream of FGF10 signaling. Finally, we also validated that both fluorescent reporters responded to FGF10 inhibition in vitro. In conclusion, these two reporter lines appear to be promising tools to monitor FGF10/FGFR2b signaling in early lung development. These tools will have to be further validated at later stages and in other organs of interest.

14.
Int Immunopharmacol ; 71: 100-108, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30884345

RESUMO

BACKGROUND: Chalcone, a natural product, has a wide range of biological activities. L2H17, a chalcone derivative, was synthesized and screened in our previous study and exhibited excellent anti-inflammatory property in vitro. This study investigated the therapeutic potential of L2H17 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of heme oxygenase-1 (HO-1). MATERIALS AND METHODS: An ALI animal model was induced by LPS (10 mg/kg) intratracheal instillation. The effect of L2H17 on LPS-induced structural damage was determined using hematoxylin and eosin (HE) staining, and tissue edema extent was examined. Bronchoalveolar lavage fluid (BALF) was harvested to assess the levels of related cytokines by enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity was also assessed. HO-1 expression was determined using immunohistochemistry and western blotting. The effects of L2H17 on LPS stimulation in RAW 264.7 and the involvement of the HO-1 pathway were investigated. RESULTS: L2H17 alleviated the histopathological manifestations and tissue edema. Moreover, L2H17 decreased the production of pro-inflammatory factors in BALF and increased SOD activity. In vitro, L2H17 significantly reduced pro-inflammatory cytokine production. Additionally, L2H17 improved the expression of HO-1 in LPS-treated lung tissue and RAW 264.7. We also found that the inhibitory effect of L2H17 on the inflammatory responses was attenuated by an inhibitor of HO-1 activity, Tin protoporphyrin IX (SnPP). CONCLUSION: Our data confirmed that L2H17 can exert protective effect on ALI in vitro and in vivo by inhibiting inflammatory responses and modulating the HO-1 pathway.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Chalconas/uso terapêutico , Heme Oxigenase-1/metabolismo , Inflamação/tratamento farmacológico , Pulmão/patologia , Macrófagos/imunologia , Proteínas de Membrana/metabolismo , Animais , Anti-Inflamatórios/química , Chalcona/análogos & derivados , Chalconas/química , Modelos Animais de Doenças , Regulação da Expressão Gênica , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/genética , Humanos , Lipopolissacarídeos/imunologia , Pulmão/efeitos dos fármacos , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Metaloporfirinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Protoporfirinas/farmacologia , Células RAW 264.7
15.
J Cell Mol Med ; 23(1): 556-567, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30467960

RESUMO

Angiogenesis has a great impact on human health, owing to its participation in development, wound healing and the pathogenesis of several diseases. It has been reported that let-7a is a tumour suppressor, but whether it plays a role in angiogenesis is unclear. Here we showed that let-7a, a microRNA conserved in vertebrates, regulated angiogenesis by concomitantly down-regulating TGFBR3. Overexpression of let-7a or knockdown of TGFBR3 in cell culture inhibited the tube formation and reduced migration rate. Moreover, xenograft experiments showed that overexpression of let-7a or knockdown of TGFBR3 had smaller tumour size. Downstream genes, such as VEGFC and MMP9, were also down-regulated in let-7a overexpression or TGFBR3 knockdown groups. Therefore, our results revealed a novel mechanism that let-7a regulate angiogenesis through post-transcriptional regulation of TGFBR3.

16.
Respiration ; 97(5): 416-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554211

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a leading cause of morbidity and mortality in China, with tobacco smoke, air pollution, and occupational biohazards being the major risk factors. OBJECTIVES: The REACH trial is a multicenter, prospective, randomized controlled trial undertaken in China to assess the safety and effectiveness of the Spiration® Valve System (SVS) compared to standard medical care in COPD patients with severe emphysema. METHODS: Patients with severe airflow obstruction, hyperinflation, and severe dyspnea with interlobar fissure integrity were evaluated for enrollment. A total of 107 subjects were randomized in a 2: 1 allocation ratio to either the treatment group (SVS valves and medical management) or the control group (medical management alone). RESULTS: The 3-month primary endpoint showed statistically significant improvement in forced expiratory volume in 1 s in the treatment group compared to the control group (0.104 ± 0.18 vs. 0.003 ± 0.15 L, p = 0.001), with the difference being durable through 6 months. Statistically significant target lobe volume reduction was achieved at 3 months (mean change 684.4 ± 686.7 mL) and through 6 months (757.0 ± 665.3 mL). Exercise function and quality of life measures improved in the treatment group, but showed a deterioration in the control group. The serious adverse event (SAE) rate was 33% in the treatment group and 24.2% in the control group. The predominance of SAEs were acute exacerbations of COPD in both groups. There was 1 death in the control group and no deaths in the treatment group. CONCLUSION: The SVS represents a novel approach for the treatment of severe emphysema with a clinically acceptable risk-benefit profile.

17.
BMC Pulm Med ; 18(1): 192, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30526587

RESUMO

BACKGROUND: The optimal procedure for maximizing the diagnostic yield and minimizing the procedural complexity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is controversial. We conducted a prospective randomized controlled trial to determine the optimal procedure of EBUS-TBNA for mediastinal and hilar lymphadenopathy, with a particular focus on the roles of the inner-stylet and suction. METHODS: Consecutive patients with enlarged mediastinal and hilar lymph nodes (LNs), detected by computed tomography (CT) or positron emission tomography-CT (PET-CT), who underwent EBUS-TBNA were included. Each LN was sampled with three needle passes using suction-stylet, suction-no stylet, and stylet-no suction procedures. The samples were smeared onto glass slides for cytological evaluation. A single, blinded cytopathologist evaluated each set of slides. The primary outcomes were cytological specimen adequacy rate and diagnostic yield of malignant LNs. The secondary outcomes were tissue-core acquisition rate, procedural time, and the amount of bleeding. RESULTS: This study evaluated 97 patients with a total of 255 LNs. The final LN diagnosis was benign in 144, malignant in 104, and inadequate in 7 cases. There were no significant differences among the suction-stylet, suction-no stylet, and stylet-no suction groups in specimen adequacy rate (87.1, 88.2, 85.9%, respectively) or diagnostic yield of malignancy (32.2, 31.8, 31.0%, respectively). However, the use of suction was associated with an increase in tissue-core acquisition rate (P <  0.001). The no-stylet procedure decreased the average procedural time by 14 s (P <  0.001). There was no significant difference in the amount of bleeding among the procedures. CONCLUSIONS: The use of suction or non-use of an inner-stylet does not make a significant difference in cytological specimen adequacy or diagnostic yield when performing EBUS-TBNA. While omitting the stylet can simplify the procedure, applying suction can increase the tissue-core acquisition rate. These findings may assist endoscopic physicians in determining the optimal EBUS-TBNA procedure and warrant clinical verification in a future multicentre study. TRIAL REGISTRATION: Trial registration: ( ChiCTR-IOR-17010616 ). Retrospective registered date: 12th February, 2017.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfonodos/patologia , Linfadenopatia , Neoplasias/patologia , Manejo de Espécimes/métodos , Idoso , Precisão da Medição Dimensional , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Humanos , Linfadenopatia/diagnóstico , Linfadenopatia/patologia , Masculino , Mediastino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
18.
Front Genet ; 9: 545, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30487814

RESUMO

During organogenesis and pathogenesis, fibroblast growth factor 10 (Fgf10) regulates mesenchymal cell differentiation in the lung. Different cell types reside in the developing lung mesenchyme. Lineage tracing in vivo was used to characterize these cells during development and disease. Fgf10-positive cells in the early lung mesenchyme differentiate into multiple lineages including smooth muscle cells (SMCs), lipofibroblasts (LIFs) as well as other cells, which still remain to be characterized. Fgf10 signaling has been reported to act both in an autocrine and paracrine fashion. Autocrine Fgf10 signaling is important for the differentiation of LIF progenitors. Interestingly, autocrine Fgf10 signaling also controls the differentiation of pre-adipocytes into mature adipocytes. As the mechanism of action of Fgf10 on adipocyte differentiation via the activation of peroxisome proliferator-activated receptor gamma (Pparγ) signaling is quite well established, this knowledge could be instrumental for identifying drugs capable of sustaining LIF differentiation in the context of lung injury. We propose that enhanced LIF differentiation could be associated with improved repair. On the other hand, paracrine signaling is considered to be critical for the differentiation of alveolar epithelial progenitors during development as well as for the maintenance of the alveolar type 2 (AT2) stem cells during homeostasis. Alveolar myofibroblasts (MYFs), which are another type of mesenchymal cells critical for the process of alveologenesis (the last phase of lung development) express high levels of Fgf10 and are also dependent for their formation on Fgf signaling. The characterization of the progenitors of alveolar MYFs as well the mechanisms involved in their differentiation is paramount as these cells are considered to be critical for lung regeneration. Finally, lineage tracing in the context of lung fibrosis demonstrated a reversible differentiation from LIF to "activated" MYF during fibrosis formation and resolution. FGF10 expression in the lungs of idiopathic pulmonary fibrosis (IPF) vs. donors as well as progressive vs. stable IPF patients supports our conclusion that FGF10 deficiency could be causative for IPF progression. The therapeutic application of recombinant human FGF10 is therefore very promising.

19.
J Thorac Dis ; 10(3): E194-E198, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29707372

RESUMO

Upper tracheal stenosis is considered as a potentially life-threatening condition. Silicone stenting is an attractive treatment option for patients with upper tracheal stenosis. However, its use has been compromised by a major complication, stent migration. In the report, we introduced a novel external fixation of silicone stent which only needed one puncture site and involved a silicon chip as an anchoring device. All equipment and materials including the silicon chip were available in routine bronchoscopy suite. The method had been successfully performed in three patients with upper tracheal stenosis at our institution. And the patients were monitored for over 20 months after the intervention, and no spontaneous stent migration occurred. Therefore, we believe this is a simple and reliable approach for improving the outcome of silicone stenting in patients with upper tracheal stenosis and should be introduced in clinical practice.

20.
Cell Biol Toxicol ; 34(1): 39-49, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28638955

RESUMO

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells. Our data illustrated that the expression levels of CCN1 and IL-6 in bronchoalveolar lavage fluid (BALF) in a lipopolysaccharide (LPS)-induced ALI mouse model were significantly elevated and the pulmonary expression of CCN1 was restricted to bronchial epithelial cells. Interestingly, both endogenous and exogenous CCN1 stimulated IL-6 production in vitro. Furthermore, LPS-induced IL-6 production in a bronchial epithelial cell line was blocked by CCN siRNA whereas CCN1 induced by LPS was sensitive to PI3K inhibition. Together, our data indicate a linear signal pathway, LPS-CCN1-IL-6, existing in bronchial epithelial cells after LPS exposure. This finding may represent an additional mechanism and a novel target for development of therapy and biomarker on ALI/ARDS.


Assuntos
Brônquios/citologia , Proteína Rica em Cisteína 61/biossíntese , Células Epiteliais/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Células Epiteliais/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA