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Trigonelline mitigates bleomycin-induced idiopathic pulmonary fibrosis in mice

Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 391-400,I0008-I0291页

作者： Swapnil Gavhane Chandrakant Gawli Sachin Kumar Biswajit Das Gayatri Marathe Vishal S.Patil Harun M.Patel Basavaraj Bommanahalli Chanakya Nath Kundu Chandragouda R.Patil R.C.Patel Institute of Pharmaceutical Education and Research Karwand NakaShirpurMaharashtra 425405India Department of Pharmacology Delhi Pharmaceutical Sciences and Research UniversityNew Delhi 110017India School of Biotechnology Kalinga Institute of Industrial TechnologyBhubaneshwar 751024India Gadag Institute of Medical Sciences GadagKarnataka 582103India

Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network ***:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th *** IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were *** alterations in lung tissues were also ***,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of ***:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of ***,trigonelline alleviated bleomycin-induced histological alterations in lung *** pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and ***:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating *** may be considered an antifibrotic agent for further clinical development.

关键词： Trigonelline Idiopathic pulmonary fibrosis Antifibrotic bleomycin Network pharmacology

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Investigating the mechanism of action of Bu-Yang-Huan-Wu decoction in treating bleomycin-Induced pulmonary fibrosis through the epithelial-mesenchymal transition pathway

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Toxicology Advances 2024年第1期6卷 10-15页

作者： Yu-Ming Wang Han-Zhou Li Huan-Tian Cui Yu-Hong Bian Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China College of Integrated Traditional Chinese and Western Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China The First Affiliated Hospital Yunnan University of Chinese MedicineKunming 650500China

Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in ***:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu *** fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg *** the control group,mice were given a solitary intratracheal administration of a comparable volume of *** began on the first day after the successful model establishment and lasted for 21 *** survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total *** wet/dry weight ratio of lung tissue and hydroxyproline were *** tissue pathology was observed using hematoxylin and eosin staining and Masson *** mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western ***:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline *** pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and ***:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.

关键词： pulmonary fibrosis Bu-Yang-Huan-Wu decoction epithelial-mesenchymal transition bleomycin

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Studies on the Electrochemical Behavior of bleomycin at a Co/GC Ion Implantation Modified Electrode and Its Application

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Chemical Research in Chinese Universities 2001年第4期17卷 362-367页

作者： HU Jing-bo LI Qi-long Department of Chemistry Beijing Normal UniversityBeijing 100875P.R.China

In a 0. 10 mol/L HAc-NaAc buffer solution (pH = 4. 59), a sensitive reduction peak of bleomycin was observed by linear sweep voltammetry at a Co/GC ion implantation modified electrode. The peak potential was-0. 73 V(iw. SCE). The peak current was proportional to the concentration of bleomycin over the range of 5.0 × 10-8-1.0× 10-6 and 1.0× 10-6-1. 0 × 10-5 mol/L with a detection limit of 2.0 × 10-8 mol/L. The electrochemical behavior of the reduction peak of bleomycin at the Co/GC modified electrode was studied by linear sweep and cyclic voltammetry and applied to the determination of bleomycin in urine. This method is simple, rapid and reliable. The reduction process is quasi-reversible. The experiments of AES and XPS showed that Co was surely implanted into the surface of GCE and the depth distribution of Co was in good agreement with Gooses normal distribution; the implanted Co at GCE improved the electrocatalytic activity.

关键词： Co/GC ion implantation modified electrode Electrochemical behavior Linear sweep voltammetry bleomycin

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Remarkable enhancement of bleomycin production through precise amplification of its biosynthetic gene cluster in Streptomyces verticillus

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Science China(Life Sciences) 2022年第6期65卷 1248-1256页

作者： Hong Li Wenyan Gao Yifan Cui Yuanyuan Pan Gang Liu State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China The Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100864China

Amplification of biosynthetic gene clusters is important to increase secondary metabolite ***,the copy number of amplified gene clusters is difficult to control *** this study,the tandem amplification of a 70 kb bleomycin biosynthetic gene cluster was precisely regulated through the combined strategy of a Zou A-dependent DNA amplification system and double-reporter-guided recombinant selection in Streptomyces verticillus *** production of bleomycin in the recombinant strain containing six copies of the bleomycin gene cluster was 9.59-fold higher than that in the wild-type *** combined strategy used in this study is powerful and applicable for precisely regulating the amplification of gene clusters and improving the corresponding secondary metabolite production.

关键词： bleomycin precise regulation amplification of gene cluster strain improvement

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Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation

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Journal of Molecular Cell Biology 2014年第6期8卷 506-515页

作者： Tao Cheng Qingbo Liu Rui Zhang Ying Zhang Jianfeng Chen Ronghuan Yu Gaoxiang Ge State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031 China Department of Respiratory Medicine Shanghai Xu-Hui Central Hospital Shanghai 200031 China Cancer Research Center Shanghai Xu-Hui Central Hospital Shanghai Clinical Center Chinese Academy of Sciences Shanghai 200031 China

Enzymes involved in collagen biosynthesis, including lysyl oxidase （LOX）, have been proposed as potential therapeutic targets for idio- pathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin （BLM）-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory ceU infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expres- sion of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subse- quent fibrosis process after lung injury.

关键词： lysyl oxidase lung fibrosis inflammation bleomycin animal models extracellular matrix

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Pyunkang-hwan (Pyunkang-Tang) ameliorates air pollutant-induced inflammatory hypersecretion of airway mucus and bleomycin-induced pulmonary fibrosis in rats

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Journal of Traditional Chinese Medicine 2016年第5期36卷 663-670页

作者： Hyo-Seok Seo Hyun Jae Lee Choong Jae Lee Department of Pharmacology School of Medicine Chungnam National University Department of Health Management Sahmyook University

OBJECTIVE: To investigate the effect of Pyunkanghwan(Pyunkang-tang) extract(PGT) on secretion of airway mucin in an experimental animal model involving hyperplasia of goblet cells and mucus hypersecretion, and to test its effects on bleomycin(BLM)-induced pulmonary fibrosis in ***: The protective activity of orally administered PGT was assessed in two rat pulmonary disease models. Effects on hypersecretion of pulmonary mucin in sulfur dioxide(SO_2)-induced bronchitis in rats were assessed by quantifying the amount of mucus secreted and examining histopathology in the tracheal epithelium. In a rat model for BLMinduced pulmonary fibrosis, toxicity to the pulmonary system was examined by measuring levels of malondialdehyde and hydroxyproline,indicators of lipid peroxides and collagen,respectively, in lung tissue 28 days post-BLM treatment. Serial sections of lung tissue were stained with Masson trichrome to visualize collagen deposition. Effects of PGT on collagen synthesis were also assessed in vitro, in a cell culture ***: PGT inhibited mucin secretion and normalized SO_2-induced increased muco- substances in goblet cells. In the BLM- induced model,PGT decreased the characteristic histopathological features of lung fibrosis and inhibited fibrotic lesions, as indicated by decreased hydroxyproline content. PGT also inhibited the BLM-induced increase in malondialdehyde levels, demonstrating its protective effect against lipid peroxidation in cell membranes of the lung. In MLg 2908 mouse lung fibroblast cells, PGT decreased transforming growth factor(TGF)-β-stimulated type I collagen ***: PGT can inhibit both hypersecretion of airway mucins and pulmonary fibrosis.

关键词： Pyunkang-hwan(Pyunkang-tang) Air pollutants bleomycin Pulmonary fibrosis Airway mucin

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Cyclophosphamide abrogates the expansion of CD4^(+)Foxp3^(+) regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas

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Cancer Biology & Medicine 2021年第4期18卷 1010-1020页

作者： Ping Li Fengyang Chen Jingbin Zheng Yang Yang Yuan Li Yifei Wang Xin Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical ScienceUniversity of MacaoMacao 999078China

Objective:Promotion of the proliferative expansion of CD4^(+)Foxp3^(+)regulatory T cells(Tregs)is one of the side effects that limits the use of bleomycin(BLM)in the treatment of *** this study,we examined the hypothesis that cyclophosphamide(CY),a chemotherapeutic agent with the capacity to eliminate tumor infiltrating Tregs,abrogated BLM-induced expansion of Tregs and consequently resulted in a better anti-tumor ***:The in vitro effects of BLM,with or without mafosfamide(MAF,the active metabolite of CY),on both TGF-β-induced differentiation of Tregs(iTregs),and TNF-induced expansion of naturally occurring Tregs(nTregs)were *** in vivo effect of low doses of BLM and CY on tumor-infiltrating Tregs,as well as on the growth of mouse B16-F10 melanomas,was also ***:In vitro treatment with BLM promoted the differentiation of iTregs,as well as TNF-induced expansion of *** effects of BLM were completely abrogated by ***,in the mouse B16-F10 melanoma model,treatment with low doses of BLM increased the number of tumor-infiltrating Tregs,and this effect of BLM was also abrogated by ***,combination therapy with low doses of BLM and CY showed synergistic anti-tumor ***:CY abrogated the effect of BLM on the expansion of *** combination of these 2 chemotherapeutic agents may represent a safer and more effective therapy in the treatment of cancer patients,and thus merits future clinical evaluation.

关键词： bleomycin cyclophosphamide tumor necrosis factor Tregs TNFR2

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(5R)-5-hydroxytriptolide (LLDT-8) protects against bleomycin-induced lung fibrosis in mice

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Acta Pharmacologica Sinica 2007年第4期28卷 518-525页

作者： Yong-xin REN,Ru ZHOU~2,Wei TANG~2,Wen-hai WANG~2,Yuan-chao LI~3,Yi-fu YANG~2,Jian-ping ZUO~(2,4)~2Laboratory of Immunopharmacology and ~3Laboratory of Chemistry,State Key Laboratory of Drug Research,Shanghai Institute of MateriaMedica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203 China Laboratory of Immunopharmacology State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Laboratory of Chemistry State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To study the protective effects of a triptolide-derived,novel compound,(5R)-5-hydroxytriptolide (LLDT-8),on bleomycin-induced lung ***:C57BL/6 mice received an intratracheal injection of bleomycin and were then treatedwith LLDT-8 (0.5,1,2 mg/kg,ip) once daily for 7 or 14 consecutive *** bodyweight loss and lung index augmentation was observed;the inflammatory re-sponse including differential cells counts of neutrophils,macrophages,and lym-phocytes in the bronchoalveolar lavage fluid (BALF),superoxide dismutase (SOD),and malondialdehyde (MDA) level in the lung homogenates was detected,andthe fibrosis extent was evaluated by hydroxyproline content and histopathologi-cal changes in the *** addition,the pro-inflammatory and pro-fibroticcytokines,tumor necrosis factor-α(TNF-α),interleukin-4 (IL-4),and transforminggrowth factor-α (TGF-α) production in the lungs were ***:LLDT-8alleviated the body weight loss and lung index increase caused by bleomycin,reduced neutrophils and lymphocytes in the BALF,promoted SOD activity,decreased MDA production,and inhibited the hydroxyproline level and the amelio-ration of lung tissue histological ***,LLDT-8 suppressed TNF-α,1L-4,and TGF-β production in the lung ***:LLDT-8 showedprotective effects against bleomycin-induced lung fibrosis,and the resultssuggested the potential role of LLDT-8 in the treatment of this disease.

关键词： (5R)-5-hydroxytriptolide bleomycin lung fibrosis cytokines

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The Electrochemical Behavior of bleomycin at A Co/GC Ion Implantation Modified Electrode

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Chinese Chemical Letters 1999年第10期10卷 855-856页

作者： Jing Bo HU Qi Long LI (Department of Chemistry, Beijing Normal University, Beijing 100875) Department of Chemistry Beijing Normal University Beijing 100875 China

In 0.10 mol/L HOAc-NaOAc buffer solution (pH 4.59). a sensitive reduction peak of bleomycin is obtained by linear sweep voltammetry at Co/GC ion implantation modified electrode. Its electrochemical behavior has been studied. The experiments of AES and XPS show that Co is surely implanted into the surface of GCE and improved the electrocatalytic activity.

关键词： ion implantation electrochemical behavior bleomycin

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Studies on Electrochemical Behavior of bleomycin and Its Interaction with DNA at a Co/GC Ion Implantation Modified Electrode

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Chinese Journal of Chemistry 2002年第3期20卷 267-271页

作者：胡劲波李启隆尚军 Department of Chemistry Beijing Normal University Beijing 100875 China

Electrochemical investigation of bleomycin (BLM) and its interaction with DNAat a Co/GC ion implantation modified electrode was reported for the first time. The electrochemicalbehavior of BLM at Co/GC modified electrode has been studied by linear sweep and cyclicvoltammetry, The reaction of BLM with DNA formed an electrochemically nonactive complex, whichresulted in a decrease in the BLM equilibrium concentration and its reduction current. The decreasein peak current was proportional to DNA concentration and could be used to determination DNAconcentration. The equilibrium constant of DNA-BLM complex β was determined to be 5.16 x 10^(16).The experiments of AES and XPS showed that Co was surely implanted into the surface of GCE( glassycarbon electrode) and the depth distribution of Co was in good agreement with Gaussian normaldistribution; the implanted Co at GCE improved the electrocatalytic activity.

关键词： Co/GC ion implantation modified electrode linear sweep voltammetry bleomycin DNA

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