المؤلفون: Jiunn-Liang Ko, Ko-Haung Lue, Yu-Tzu Lee, Chia-Ta Wu, Peng-Jung Chen

المصدر: Journal of Microbiology, Immunology and Infection. 49(5):625-635

مصطلحات موضوعية: 0301 basic medicine, Lactobacillus rhamnosus GG, Allergy, Anti-Inflammatory Agents, Immunoglobulin E, Mice, 0302 clinical medicine, Medicine, Immunology and Allergy, Lung, Sensitization, Methacholine Chloride, Mice, Inbred BALB C, biology, medicine.diagnostic_test, Lacticaseibacillus rhamnosus, General Medicine, respiratory system, medicine.anatomical_structure, Infectious Diseases, Matrix Metalloproteinase 9, Cytokines, Female, medicine.symptom, Bronchoalveolar Lavage Fluid, medicine.drug, Microbiology (medical), airway hyper-responsiveness, Ovalbumin, Inflammation, 03 medical and health sciences, Lactobacillus rhamnosus, Immunology and Microbiology(all), Animals, General Immunology and Microbiology, business.industry, Probiotics, biology.organism_classification, medicine.disease, Asthma, respiratory tract diseases, Disease Models, Animal, 030104 developmental biology, Bronchoalveolar lavage, 030228 respiratory system, Immunology, biology.protein, Methacholine, business

الوصف: Background Asthma is a common allergic disease. In previous studies, probiotics improved the balance of intestinal microbes, reduced inflammation, and promoted mucosal tolerance. This study investigated whether oral administrations of Lactobacillus rhamnosus GG (LGG) inhibited allergen (ovalbumin or OVA)-induced airway inflammation in a mouse asthma model. Methods The allergy/asthma animal model in this study was sensitization with OVA. After intranasal challenge with OVA, the airway inflammation and hyper-responsiveness were determined by a Buxco system, bronchoalveolar lavage fluid analysis with Liu stain, and enzyme-linked immunosorbent assay. Histopathologic changes in the lung were detected by hematoxylin and eosin staining and immunohistochemistry staining. Results Both pre- and post-treatment with LGG suppressed the airway hyper-responsiveness to methacholine and significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid and serum compared with the OVA-sensitized mice. In addition, LGG reduced OVA-specific IgE levels in serum. Oral LGG decreased matrix metalloproteinase 9 expression in lung tissue and inhibited inflammatory cell infiltration. Conclusion LGG had an anti-inflammatory effect on OVA-induced airway inflammation and might be an additional or supplementary therapy for allergic airway diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::40f04ff031b6f5ac9346613566575e91Test

المؤلفون: Jiunn-Liang Ko, Gwo-Tarng Sheu, Yang Ty, Chi Jy, Hsin Il, Chiu Ly, Wen-Wei Sung, Jinghua Tsai Chang

المصدر: Oncogene

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Vinca, Epithelial-Mesenchymal Transition, Lung Neoplasms, MAP Kinase Signaling System, Pemetrexed, Pharmacology, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Line, Tumor, Genetics, medicine, Animals, Humans, Epithelial–mesenchymal transition, Lung cancer, Molecular Biology, Vinca Alkaloids, A549 cell, biology, Cancer, Zinc Finger E-box-Binding Homeobox 1, biology.organism_classification, medicine.disease, Prognosis, Xenograft Model Antitumor Assays, Vinblastine, Up-Regulation, Gene Expression Regulation, Neoplastic, 030104 developmental biology, A549 Cells, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer cell, Original Article, Tumor Suppressor Protein p53, medicine.drug

الوصف: High thymidylate synthase (TS) level in cancer tissue is considered to result in resistance to pemetrexed therapy for advanced stages of nonsquamous non-small cell lung cancers. To further investigate the mechanism of pemetrexed resistance and potential prognostic outcomes in lung cancer, we established pemetrexed-resistant lung adenocarcinoma cell sublines from CL1 harboring a mutated TP53 gene (R248W) and A549 harboring wild-type TP53. We found the TS expression is upregulated in both pemetrexed-resistant sublines and the reduced TS level achieved through shRNA inhibition resulted in higher pemetrexed sensitivity. We also demonstrated that the acquisitions of pemetrexed resistance enhances epithelial-mesenchymal transition (EMT) in vivo with a mice animal model and in vitro with CL1 and A549 sublines, which was associated with upregulation of ZEB1 which, in turn, downregulates E-cadherin and upregulates fibronectin. When ERK1/2 phosphorylation was reduced by an inhibitor (U0126) or siRNA inhibition, both pemetrexed-resistant sublines reduced their migration and invasion abilities. Therefore, the ERK-mediated pathways induce apoptosis with pemetrexed treatment, and may in turn mediate EMT when cancer cells are resistant to pemetrexed. We further demonstrated that the growth of pemetrexed-resistant tumors could be inhibited by vinblastine in vivo and vincristine in vitro. Our data indicate that pemetrexed resistance could be relieved by non-cross-resistant chemotherapeutic drugs such as vinca alkaloids and might be independent to TP53 status. Furthermore, the phosphorylation of ERK was reduced by vincristine. This finding provides a new insight for overcoming pemetrexed resistance and metastasis by application of vinca alkaloids.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab0e172f305f6bb915bd0bbe34da3165Test
https://pubmed.ncbi.nlm.nih.gov/27270426Test