Publications by authors named "Yunfeng Ni"

21 Publications

  • Page 1 of 1

Dynamin 3 Inhibits the Proliferation of Non-small-Cell Lung Cancer Cells by Suppressing c-MET-GBR2-STAT3 Complex Formation.

Front Cell Dev Biol 2021 19;9:641403. Epub 2021 Aug 19.

The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Department of Health Statistics, School of Public Health, The Air Force Military Medical University, Xi'an, China.

Dynamin 3 (DNM3) has gained increased attention ever since its potential as a tumor suppressor was reported. However, its action in lung cancer (LC) is undefined. In this study, the role of DNM3 in LC development was investigated. DNM3 expression was found to be downregulated in tumors of patients with LC, especially those with metastasis. The DNM3 downregulation enhanced the proliferative and metastatic ability of LC cells, whereas its upregulation had the opposite effects. xenograft experiments confirmed that lung tumors with lower DNM3 expression had higher growth and metastatic abilities. Mechanistic studies revealed that DNM3 interacts with growth factor receptor-bound protein 2 (GBR2), thereby interrupting tyrosine-protein kinase Met (c-MET)-GBR2-signal transducer and activator of transcription 3 (STAT3) complex formation, which suppressed STAT3 activation. Therefore, the absence of DNM3 frees GBR2 to activate STAT3, which regulates the expression of genes related to LC proliferation and metastasis (e.g., cyclin D1 and Snail family transcriptional repressor 1). Additionally, the c-MET inhibitor crizotinib effectively suppressed LC cell proliferation and migration and , even with DNM3 depleted. Therefore, our study has demonstrated the antitumor effect of DNM3 in LC and suggests that the inhibition of c-MET might be a promising strategy for treating those LC patients with low DNM3 expression.
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http://dx.doi.org/10.3389/fcell.2021.641403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416685PMC
August 2021

CircRIP2 promotes NSCLC progression by sponging for miR-671-5p to regulate FOXM1 expression.

Histol Histopathol 2021 Jul 22:18360. Epub 2021 Jul 22.

Department of Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.

Lot of attention had been paid to the role of circular RNAs (circRNAs) in carcinogenesis recently. However, knowledge about circRNAs in NSCLC development is far from satisfactory. In this study, we aimed to provide a novel insight into the circRIP2 in NSCLC development. We used NSCLC tissues, as well as cell lines to elucidate the expression and location of circRIP2 in NSCLC. We also established the circRIP2 overexpression cells A549-circRIP2 and repression cells HCC827-shcircRIP2 for further functional and mechanism studies. The pro-tumorigenic role of circRIP2 was tested by using CCK-8, BrdU and transwell assays. The interaction between circRIP2 and miR-671-5p were validated by luciferase reporter assay, RIP assay, as well as RNA pull down assay. We showed circRIP2 is differentially expressed NSCLC, and acted as a predictor for overall survival (OS) and disease-free survival (DFS). CircRIP2 promoted NSCLC progression by acting as a miRNA sponge for miR-671-5p, thus facilitating its target gene FOXM1 expression. Targeting circRIP2 could be potentially beneficial for NSCLC patients in the future.
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http://dx.doi.org/10.14670/HH-18-360DOI Listing
July 2021

Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.

J Immunol Res 2020 15;2020:5097920. Epub 2020 Oct 15.

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

In this study, the effects of single immunoglobin IL-1 receptor-related protein (SIGIRR) on tumor necrosis factor- (TNF-) receptor-associated factor 6 (TRAF6) ubiquitination in acute lung injury (ALI) were evaluated in both alveolar epithelial cells and alveolar macrophage cells in vitro. Our results found that SIGIRR negatively regulated TRAF6 ubiquitination and such SIGIRR inhibition could enhance the TRAF6 expression in both alveolar epithelial cells (AECs) and alveolar macrophage cells (AMCs). SIGIRR knockdown may increase NF-B activity via TRAF6 regulation by the classical but not the nonclassical NF-B signaling pathway. Such modulation between TRAF6 and SIGIRR could affect cytokine secretion and exacerbate the immune response; the IL-8, NFKB1, and NFKBIA mRNA levels were reduced after SIGIRR overexpression. The current study reveals the molecular mechanisms of the negative regulatory roles of SIGIRR on the innate immune response related to the LPS/TLR-4 signaling pathway and provides evidence for strategies to clinically treat inflammatory diseases.
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http://dx.doi.org/10.1155/2020/5097920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584944PMC
July 2021

Restoration of the Antibiotic Susceptibility of Methicillin-Resistant and Extended-Spectrum β-Lactamases Through Combination with Chelerythrine.

Microb Drug Resist 2021 Mar 24;27(3):337-341. Epub 2020 Jul 24.

Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, People's Republic of China.

Multidrug resistance poses a severe threat to public health and urgently requires new solutions. The natural product chelerythrine (CHE) is a benzophenanthridine alkaloid with antimicrobial potential. In this study, CHE was effective against seven gram-positive bacterial strains, and the minimum inhibitory concentrations (MICs) ranged from 2 to 4 μg/mL. By contrast, CHE showed inferior antibacterial activities against 11 gram-negative strains, and the MICs varied from 16 to 256 μg/mL. We also determined the synergistic/additive effects of combining CHE with nine currently used antibiotics. CHE restored the antibacterial efficacy of the antibiotics against methicillin-resistant and extended-spectrum β-lactamases producing . This study suggests that the combination of CHE with conventional antibiotics may be a promising strategy to combat infections caused by multidrug-resistant organisms.
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http://dx.doi.org/10.1089/mdr.2020.0044DOI Listing
March 2021

SUMO1 promotes the proliferation and invasion of non-small cell lung cancer cells by regulating NF-κB.

Thorac Cancer 2019 01 4;10(1):33-40. Epub 2018 Nov 4.

Department of Thoracic Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, China.

Background: Our previous study showed that SUMO1 expression is closely related to progression in non-small cell lung cancer (NSCLC); however, the function of SUMO1 in NSCLC has not yet been well elucidated.

Methods: SUMO1 was enhanced or silenced in two NSCLC cell lines by using either forced SUMO1 expression or short hairpin RNA against SUMO1 lentiviral vectors, respectively. The biological functions of SUMO1 in NSCLC were investigated through colony-formation, cell proliferation, and invasion assays, and cell cycle analysis. NF-κB expression was detected in the overexpressed and silenced SUMO1 cell lines. Immunohistochemistry was used to detect an association between SUMO1 and NF-κB in the cancer and adjacent tissues of 168 patients with lung cancer.

Results: Overexpressed SUMO1 promoted the proliferation rate, colony formation ability, invasion, and NF-κB expression in an A549 cell line. Conversely, SUMO1 depletion inhibited the cell growth rate, colony formation ability, invasion, and NF-κB expression in a Calu-1 cell line. SUMO1 expression was significantly correlated with NF-κB expression in lung adenocarcinoma and squamous carcinoma patients (r > 0.5, P < 0.001).

Conclusion: Our results provide evidence that SUMO1 promotes the proliferation and invasion of NSCLC cells by regulating NF-κB.
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http://dx.doi.org/10.1111/1759-7714.12895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312836PMC
January 2019

PLGA-PTMC-Cultured Bone Mesenchymal Stem Cell Scaffold Enhances Cartilage Regeneration in Tissue-Engineered Tracheal Transplantation.

Artif Organs 2017 May 7;41(5):461-469. Epub 2016 Dec 7.

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

The treatment of long-segment tracheal defect requires the transplantation of effective tracheal substitute, and the tissue-engineered trachea (TET) has been proposed as an ideal tracheal substitute. The major cause of the failure of segmental tracheal defect reconstruction by TET is airway collapse caused by the chondromalacia of TET cartilage. The key to maintain the TET structure is the regeneration of chondrocytes in cartilage, which can secrete plenty of cartilage matrices. To address the problem of the chondromalacia of TET cartilage, this study proposed an improved strategy. We designed a new cell sheet scaffold using the poly(lactic-co-glycolic acid) (PLGA) and poly(trimethylene carbonate) (PTMC) to make a porous membrane for seeding cells, and used the PLGA-PTMC cell-scaffold to pack the decellularized allogeneic trachea to construct a new type of TET. The TET was then implanted in the subcutaneous tissue for vascularization for 2 weeks. Orthotopic transplantation was then performed after implantation. The efficiency of the TET we designed was analyzed by histological examination and biomechanical analyses 4 weeks after surgery. Four weeks after surgery, both the number of chondrocytes and the amount of cartilage matrix were significantly higher than those contained in the traditional stem-cell-based TET. Besides, the coefficient of stiffness of TET was significantly larger than the traditional TET. This study provided a promising approach for the long-term functional reconstruction of long-segment tracheal defect, and the TET we designed had potential application prospects in the field of TET reconstruction.
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http://dx.doi.org/10.1111/aor.12805DOI Listing
May 2017

Crocin attenuates lipopolysacchride-induced acute lung injury in mice.

Int J Clin Exp Pathol 2015 1;8(5):4844-50. Epub 2015 May 1.

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University Xi'an 710038, China.

Crocin, a representative of carotenoid compounds, exerts a spectrum of activities including radical scavenger, anti-microbial and anti-inflammatory properties. To investigate the protective effect of crocin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intragastric injection of crocin (50 mg/kg) 1 h before LPS administration. Pulmonary histological changes were evaluated by hematoxylineosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitric oxide (NO), and myeloperoxidase (MPO) activity were measured by enzymelinked immunosorbent assay. Expression of inducible nitric oxide synthase (iNOS) in lung tissues was determined by Western blot analysis. Crocin pretreatment significantly alleviated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by crocin pretreatment. Crocin pretreatment also reduced the concentrations of NO in lung tissues. Furthermore, the expression of iNOS was significantly suppressed by crocin pretreatment. Croncin potently protected against LPS-induced ALI and the protective effects of crocin may attribute partly to the suppression of iNOS expression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503048PMC
May 2016

Benign esophago-pulmonary fistula complicating achalasia: case report and literature review.

J Thorac Dis 2015 Apr;7(4):E92-6

1 Department of Thoracic Surgery, Shanxi Provincial People's Hospital, Xi'an 710068, China ; 2 Department of Thoracic surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

The achalasia, a common benign disease of esophagus, plays an important role in esophago-respiratory fistula, which has not yet been well recognized. In present study, a case is reported of a patient with benign esophago-pulmonary fistula secondary to a longstanding achalasia. To our knowledge, this is the fifth patient of English literature presenting benign esophago-pulmonary fistula associated with achalasia, we performed Heller's myotomy as well as fundoplication through trans-abdominal route and colon replacement of the esophagus through retro-sternal procedure, but with the thoracic esophageal fistula as well as the right lung left being intact. The patient is going on well in the follow up.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2015.04.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419293PMC
April 2015

Suppression of microRNA-18a expression inhibits invasion and promotes apoptosis of human trophoblast cells by targeting the estrogen receptor α gene.

Mol Med Rep 2015 Aug 4;12(2):2701-6. Epub 2015 May 4.

Department of Obstetrics and Gynecology, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.

The purpose of the present study was to gain further understanding of the function of microRNA-18a (miR-18a) expression in the JEG-3 human trophoblast cell line. JEG-3 cells were transfected with pre-miR-18a mimics or miR-18a inhibitors. The effects of miR-18a on trophoblast cell invasion and apoptosis, and on the expression of estrogen receptor α (ESRα) were analyzed using a Transwell invasion assay, flow cytometry, reverse transcription-polymerase chain reaction, western blot analysis and a luciferase assay. The results of the present study suggested that miR-18a expression suppression led to a decrease in JEG-3 cell invasion and an increase in JEG-3 cell apoptosis, by inducing ESRα expression. The present study provides evidence for the involvement of miR-18a in the pathogenesis of pre-eclamptic pregnancies.
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http://dx.doi.org/10.3892/mmr.2015.3724DOI Listing
August 2015

MicroRNA-33a inhibits lung cancer cell proliferation and invasion by regulating the expression of β-catenin.

Mol Med Rep 2015 May 24;11(5):3647-51. Epub 2014 Dec 24.

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

MicroRNAs (miRNAs) are short, non‑coding RNAs that are aberrantly expressed in tumors. miRNA‑33a (miR‑33a) is closely associated with cholesterol metabolism and is essential for cellular growth. The aim of the present study was to explore the role of miR‑33a and identify its clinical significance in lung cancer cells. miR‑33a was observed to be overexpressed in the lung cancer cell lines A549 and NCI‑H460. MTT assay results demonstrated that the overexpression of miR‑33a significantly inhibited the proliferation of A549 cells, and similar results were obtained from the colony formation assay. This suggests that transfection of miR‑33a may suppress the growth of lung cancer cells. Overexpression of miR‑33a was also observed to result in marked G1/S phase cell cycle arrest in A549 and NCI‑H460 cell lines using fluorescence‑activated cell sorting analysis. Western blot analysis revealed that overexpression of miR‑33a significantly reduced the expression of β‑catenin in A549 and NCI‑H460 cells, suggesting a direct or indirect regulation of β‑catenin by miR‑33a in lung cancer cells. In conclusion, the current study may provide strategies for the treatment of lung cancer and clarify the mechanism of its progression.
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http://dx.doi.org/10.3892/mmr.2014.3134DOI Listing
May 2015

Sea-urchin-like Au nanocluster with surface-enhanced raman scattering in detecting epidermal growth factor receptor (EGFR) mutation status of malignant pleural effusion.

ACS Appl Mater Interfaces 2015 Jan 26;7(1):359-69. Epub 2014 Dec 26.

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University , Xi'an, Shaanxi 710038, China.

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are common in patients with lung adenocarcinomas and are associated with sensitivity to the small-molecule tyrosine kinase inhibitors (TKIs). For 10%-50% of the patients who experienced malignant pleural effusion (MPE), pathological diagnosis might rely exclusively on finding lung cancer cells in the MPE. Current methods based on polymerase chain reaction were utilized to test EGFR mutation status of MPE samples, but the accuracy of the test data was very low, resulting in many patients losing the chance of TKIs treatment. Herein, we synthesized the sea-urchin-like Au nanocluster (AuNC) with an average diameter of 92.4 nm, composed of 15-nm nanopricks. By introducing abundant sharp nanopricks, the enhancement factor of AuNC reached at 1.97 × 10(7). After capped with crystal violet (CV), polyethylene glycol, and EGFR mutation specific antibody, the AuNC-EGFR had excellent surface-enhanced Raman scattering (SERS) activity and EGFR mutation targeted recognition capability in lung cancer cells. Characteristic SERS signal at 1617 cm(-1) of CV was linear correlation with the number of H1650 cells, demonstrating the minimum detection limit as 25 cells in a 1-mL suspension. The gold mass in single H1650 cells exposed to AuNC-E746_750 for 2 h ranged from 208.6 pg to 231.4 pg, which approximately corresponded to 56-62 AuNCs per cell. Furthermore, SERS was preclinically utilized to test EGFR mutation status in MPE samples from 35 patients with lung adenocarcinoma. Principal component analysis (PCA) and the support vector machine (SVM) algorithm were constructed for EGFR mutation diagnostic analysis, yielding an overall accuracy of 90.7%. SERS measurement based on sea-urchin-like AuNC was an efficient method for EGFR mutation detection in MPE, and it might show great potential in applications such as predicting gene typing of clinical lung cancer in the near future.
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http://dx.doi.org/10.1021/am508122eDOI Listing
January 2015

Evaluation of Raman spectroscopy for diagnosing EGFR mutation status in lung adenocarcinoma.

Analyst 2014 Jan;139(2):455-63

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, No 1, Xinsi Road, Xi'an, Shaanxi Province 710038, China. (X.L.) (Y.N.).

Somatic mutations in the epidermal growth factor receptor (EGFR) gene were associated with sensitivity to small molecule tyrosine kinase inhibitors for patients with lung adenocarcinomas. In this research, EGFR mutation status was analyzed by DNA sequencing in 153 lung adenocarcinoma tissues. Of these, 75 samples carried EGFR mutations, including 29 with E19del mutation, 33 with L858R mutation, 7 with T790M mutation, and 6 with multiple mutations. Then, 30 samples including 10 with wild type (wt)-EGFR, 10 with L858R and 10 with E19del mutations were selected for Raman and immunohistochemistry (IHC) analyses. After removing the spectra from normal and non-mutated regions, 441 spectra were found appropriate for Raman analysis: 149 from wt-EGFR, 135 from L858R and 157 from E19del mutations. The Raman peaks at 675, 1107, 1127 and 1582 cm(-1) were significantly increased in wt-EGFR tissues which can be attributed to specific amino acids and DNA. The Raman peaks at 1085, 1175 and 1632 cm(-1) assigned to arginine were slightly increased in L858R tissues. The overall intensity of E19del tissues was weaker than others due to exon 19 deletion that removes residues 746-750 of the expressed protein. Principal component analysis (PCA) and support vector machine (SVM) were applied for final prediction. The PCA/SVM algorithm yielded an overall accuracy of 87.8% for diagnosing L858R or E19del from wt-EGFR tissues. Finally, RS provides a simple, rapid and low-cost procedure based upon the molecular signatures for predicting EGFR mutation status.
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http://dx.doi.org/10.1039/c3an01381bDOI Listing
January 2014

Spontaneous pneumomediastinum due to paralytic rabies.

Braz J Infect Dis 2013 Jan-Feb;17(1):94-6. Epub 2013 Jan 3.

Department of Thoracic Surgery, Tangdou Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.

Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.
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http://dx.doi.org/10.1016/j.bjid.2012.04.003DOI Listing
July 2013

Isolated Crohn's disease of the esophagus with esophago-mediastinal fistula formation.

World J Surg Oncol 2012 Oct 3;10:208. Epub 2012 Oct 3.

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, PR China.

Isolated Crohn's disease of the esophagus is rare, and accurate diagnosis and treatment in its early course are difficult. Most cases are often found very late, when severe strictures or other complications have occurred. We report the case of a male 60-year-old patient with complaints of progressive dysphagia for more than two months and the sudden appearance of heartburn for seven consecutive days. Clinical examination revealed severe esophageal stricture with a suspected fistula and mediastinitis. The patient received a successful esophagectomy. The resected specimen and pathological results confirmed a deep linear ulcer, chronic and noncaseating granulomatous inflammation, as well as a circular stricture of the esophagus with fistula into the mediastinum due to isolated esophageal Crohn's disease.
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http://dx.doi.org/10.1186/1477-7819-10-208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499212PMC
October 2012

A case report of para-esophageal bronchogenic cyst with esophageal communication.

J Cardiothorac Surg 2012 Sep 26;7:94. Epub 2012 Sep 26.

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, PR China.

Paraesophageal bronchogenic cyst was one of common mediastinal congenital cystic lesions of foregut origin. Because of an intimate embryologic relationship with the esophagus, they were usually found intramural (intramural esophageal bronchogenic cysts) with the local esophageal mucosa being intact and the paraesophageal bronchogenic cysts were rarely communicated with esophageal lumen. We report a case of para-esophageal bronchogenic cyst communicating to the esophageal lumen thorough a pedicle of canal, which looked liked a diverticulum on X-ray. During the operation, a communication of paraesophageal bronchogenic cyst with esophageal was found and the pathology diagnosis were made then. The symptoms of chest pain and dysphagia were relieved immediately after operation. The follow-up was well 2 years after the surgery.
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http://dx.doi.org/10.1186/1749-8090-7-94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599576PMC
September 2012

Asterosaponin 1 induces endoplasmic reticulum stress-associated apoptosis in A549 human lung cancer cells.

Oncol Rep 2011 Oct 23;26(4):919-24. Epub 2011 Jun 23.

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.

Asterosaponin 1, a new cytostatic agent from starfish, possesses several bioactivities including an antitumor effect. The aim of this study was to investigate the potential anti-proliferative and pro-apoptotic activity of asterosaponin 1 in A549 human lung cancer cells, as well as the potential mechanisms. The results showed that asterosaponin 1 inhibited the proliferation of A549 cells in a dose-dependent manner, and the cytostatic activity resulted from the induction of apoptotic cell death. Asterosaponin 1 increased ER dilation and cytosolic Ca2+ concentration, and enhanced the expression of the ER molecular chaperones GRP78 and GRP94 in a dose- and time-dependent manner. In addition, asterosaponin 1 treated A549 cells exerted increased expression and activity of CHOP, caspase-4 and JNK, three essential ER-associated apoptotic molecules. In summary, these results demonstrated that asterosaponin 1 inhibits the proliferation of A549 cells through induction of ER stress-associated apoptosis, making asterosaponin 1 a candidate new anticancer drug for lung cancer therapy.
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http://dx.doi.org/10.3892/or.2011.1358DOI Listing
October 2011

Single immunoglobulin IL-1 receptor-related protein attenuates the lipopolysaccharide-induced inflammatory response in A549 cells.

Chem Biol Interact 2010 Feb 3;183(3):442-9. Epub 2009 Dec 3.

Department of Thoracic Surgery, Tangdu Hospital, The Forth Military Medical University. Xi'an, Shaanxi, China.

The lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4) signaling pathway in alveolar epithelial cells plays an important role in many pathologic processes such as acute lung injury (ALI). The single immunoglobulin IL-1 receptor-related protein (SIGIRR) is an inhibitor of LPS-TLR4 signaling, but its expression and function in alveolar epithelial cells are still unknown. In this study, we examined the expression of SIGIRR in normal human lung tissue using immunohistochemistry, reverse transcription-PCR (RT-PCR) and Western blot and found that SIGIRR was expressed in alveolar epithelial cells. Treatment of an alveolar epithelial cell line, A549, with LPS and we observed a downregulation of SIGIRR mRNA, which returned to normal levels 24h after LPS exposure. A549 cells were then transfected with a SIGIRR eukaryotic expression vector to over-express SIGIRR or, as a control, with an empty vector. Following LPS exposure, the transcriptional activity of NF-kappaB was measured using a dual-luciferase reporter assay system, and the concentration of IL-1beta, TNF-alpha and IL-6 was determined by ELISA, and cell proliferation was measured by MTT. In A549 cells that over-expressed SIGIRR, LPS treatment resulted in a significant decrease in the transcriptional activity of NF-kappaB and cell growth inhibition ratio, as well as lower levels of secreted IL-1beta, TNF-alpha and IL-6. In conclusion, SIGIRR in A549 cells inhibits the transcriptional activity of NF-kappaB and reduces the amount cytokines produced, protecting these cells from acute LPS-induced damage.
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http://dx.doi.org/10.1016/j.cbi.2009.11.022DOI Listing
February 2010

Bone morphogenetic protein-2 stimulation of cartilage regeneration in canine tracheal graft.

J Heart Lung Transplant 2009 Mar;28(3):285-9

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Background: Graft stenosis is among the most serious post-surgical complications that can occur after tracheal transplantation. Typically, stenosis is caused by resorption of tracheal cartilage. Bone morphogenetic protein-2 (BMP-2) is efficient at stimulating bone or cartilage regeneration. In this study, BMP-2 is tested for its effects on stimulation of cartilage regeneration in tracheal transplantation.

Methods: For tracheal autotransplantation, 24 mongrel dogs were divided equally into four groups and BMP-2 was injected between the cartilage rings at doses of 1, 3, 5 or 7 mg. For tracheal allotransplantation, 12 mongrel dogs were divided equally into two groups. One group received 5 mg of BMP-2 per graft, and the other received collagen only as a control. The grafts were harvested after 4 weeks and subjected to pathologic analysis. The diameter of the graft lumen and areas of new cartilage regeneration were measured.

Results: Regenerated cartilage areas were found in both the injected area and around the perichondrium. The areas of regenerated cartilage, as well as the diameter of the tracheal lumen, increased significantly with increasing concentrations of BMP-2. Five milligrams per milliliter was the most effective dose of BMP-2 in this study.

Conclusions: BMP-2 can significantly stimulate cartilage regeneration in tracheal grafts and also can be used to prevent stenosis after tracheal transplantation.
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http://dx.doi.org/10.1016/j.healun.2008.12.013DOI Listing
March 2009

Lung cancer A549 cells migrate directionally in DC electric fields with polarized and activated EGFRs.

Bioelectromagnetics 2009 Jan;30(1):29-35

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Endogenous direct-current electric fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials. A variety of cells respond to dcEFs by migrating directionally, and this is termed galvanotaxis. The mechanism by which dcEFs direct cell movement, however, is not yet understood, and the effects on lung cancer cells are entirely unknown. We demonstrated that cultured human lung adenocarcinoma A549 cells migrate toward the cathode in applied dcEFs at 3 V/cm. Fluorescence microscopy showed that both epidermal growth factor receptors (EGFRs) and F-actin are polarized to the cathode. EGFR inhibitors, cetuximab and AG1478, reduced the migration rate and directed motility in dcEFs. Western blots showed that ERK and AKT signaling pathways were prominently promoted by dcEFs. EGFR inhibitors could reduce this promotion but not completely. These data suggest that polarization of EGFRs and the activation of their downstream signals play an important role in the galvanotaxis of A549 cells in dcEFs.
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http://dx.doi.org/10.1002/bem.20436DOI Listing
January 2009

[The Effect of dcEFs on migration behavior of A549 cells and Integrin beta1 expression.].

Zhongguo Fei Ai Za Zhi 2008 Apr;11(2):178-82

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xian, Shanxi 710038, China.

Background: The effect of direct-current electric fields (dcEFs) on cells attracted extensive attention. Moreover the metastasis and its potential are considered to be related to dcEFs. The aim is to study the effect of dcEFs on migration behavior of A549 cells, Integrin beta1 and its signal pathways.

Methods: According to exposure to 5 V/cm dcEFs or not and the time of exposure, the A549 cells were divided into 4 groups. Images were taken per 5 min within 2 h to recode the migration of the cells. The data of results were analyzed statistically.

Results: Most of A549cells exposed to the dcEFs aligned and elongated perpendicularly to the electric field lines and migrated to the cathode continually during 2 h. On the contrary, cells unexposed to dcEFs showed slightly random movements. Immunofluorescence showed that Integrin beta1 on plasma membrane polarized to the cathode of the dcEFs. Western blot showed that Integrin beta1 downstream signal pathways p-FAK and p-ERK were overexpressed in the dcEFs.

Conclusions: A549 cells have a galvanotatic feature of cathodal directed migration while exposed to the dcEFs. The polarization of Integrin beta1 and the promotion of its downstream signal pathways may play an important roles in the galvanotaxis of A549 cells.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2008.02.028DOI Listing
April 2008
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