ABSTRACT
We proposed an optical frequency domain reflectometry based on a multilayer perceptron. A classification multilayer perceptron was applied to train and grasp the fingerprint features of Rayleigh scattering spectrum in the optical fiber. The training set was constructed by moving the reference spectrum and adding the supplementary spectrum. Strain measurement was employed to verify the feasibility of the method. Compared with the traditional cross-correlation algorithm, the multilayer perceptron achieves a larger measurement range, better measurement accuracy, and is less time-consuming. To our knowledge, this is the first time that machine learning has been introduced into an optical frequency domain reflectometry system. Such thoughts and results would bring new knowledge and optimization to the optical frequency domain reflectometer system.
ABSTRACT
Pulmonary fibrosis (PF) is an end-stage change in lung disease characterized by fibroblast proliferation, massive extracellular matrix (ECM) aggregation with inflammatory damage, and severe structural deterioration. PD29 is a 29-amino acid peptide which has the potential to alleviate PF pathogenesis via three mechanisms: anti-angiogenesis, inhibition of matrix metalloproteinase activities, and inhibition of integrins. In this study, fibrotic lung injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administered 7.5, 5, or 2.5 mg/kg PD29 daily for 30 days. BLM induced-syndromes including structure distortion, excessive deposition of ECM, excessive inflammatory infiltration, and pro-inflammatory cytokine release were used to evaluate the protective effect of PD-29. Oxidative stress damage in lung tissues was attenuated by PD29 in a dose-dependent manner. The expression of TGF-ß1 and the phosphorylation of Smad-2/-3-its downstream targets-were enhanced by BLM and weakened by PD29. In vitro, PD29 inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and transformation in A549 cells and mouse primary fibroblasts into myofibroblasts. In summary, PD29 reversed EMT and transformation of fibroblasts into myofibroblasts in vitro and prevented PF in vivo possibly by suppressing the TGF-ß1/Smad pathway.
Subject(s)
Lung/drug effects , Pulmonary Fibrosis/drug therapy , Signal Transduction/drug effects , A549 Cells , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Bleomycin , Drug Evaluation, Preclinical , Humans , Lung/metabolism , Matrix Metalloproteinases/metabolism , Mice , Primary Cell Culture , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Rats, Sprague-Dawley , Smad Proteins/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: HM-3 is a polypeptide inhibiting angiogenesis. Recent reports suggest that the antitumor effect of angiogenesis inhibitors administered alone might be limited. Cancer stem cells can survive the lack of oxygen and nutrients. To achieve better anti-tumor effect, HM-3 was administered in combination with the attenuated Salmonella typhimurium VNP20009 transformed with a shRNA construct against sex determining region Y-box 2 (Sox2). METHODS: Cell invasion assay and soft agar colony formation assay were used to assess the migration and growth capability of A549 cells once Sox2 was knocked down with the shRNA construct. The shRNA construct targeting Sox2 was transformed into VNP20009. After the mouse xenograft model of A549 was established, HM-3 was co-administered with VNP20009 carrying the shRNA construct. The growth of tumor was checked to compare the effectiveness of different therapies. Western blotting assay and immunohistochemistry staining of the tumor tissue were used to measure the levels of proteins associated with the apoptosis pathway. RESULTS: Sox2 was necessary for the migration and growth of A549 cells. The expression of Sox2 was down regulated in the tumor tissue of the combined treatment group of HM-3 with VNP20009 carrying the Sox2 shRNA construct. Together with the accumulation of salmonella in tumor and the inhibition of angiogenesis by HM-3, more tumor cells went through cell apoptosis with increased expression of Bax, cleaved Caspase 3 and decreased expression of Bcl2. CONCLUSIONS: The results suggest the combination of antiangiogenesis agent HM-3 with gene therapy targeting Sox2 delivered by salmonella as a promising strategy for the treatment of lung cancer.
