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https://www.readbyqxmd.com/read/29144435/dysregulated-collagen-homeostasis-by-matrix-stiffening-and-tgf-%C3%AE-1-in-fibroblasts-from-idiopathic-pulmonary-fibrosis-patients-role-of-fak-akt
#1
Alícia Giménez, Paula Duch, Marta Puig, Marta Gabasa, Antoni Xaubet, Jordi Alcaraz
Idiopathic pulmonary fibrosis (IPF) is an aggressive disease in which normal lung parenchyma is replaced by a stiff dysfunctional scar rich in activated fibroblasts and collagen-I. We examined how the mechanochemical pro-fibrotic microenvironment provided by matrix stiffening and TGF-β1 cooperates in the transcriptional control of collagen homeostasis in normal and fibrotic conditions. For this purpose we cultured fibroblasts from IPF patients or control donors on hydrogels with tunable elasticity, including 3D collagen-I gels and 2D polyacrylamide (PAA) gels...
November 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142410/methanolic-extract-of-costus-pictus-d-don-induces-cytotoxicity-in-liver-hepatocellular-carcinoma-cells-mediated-by-histone-deacetylase-inhibition
#2
P V Neethu, K Suthindhiran, M A Jayasri
Background: Leaves of Costus pictus D. Don, (insulin plant) are used as dietary supplement for the treatment of diabetes. Objective: The antidiabetic activity of this plant is well documented, but its activity on different cell types and mechanism remains unknown. Thus, the present study evaluates the cytotoxicity of C. pictus methanolic extract (CPME) against various cancer and normal cells. Materials and Methods: Dried leaves of C. pictus were extracted using methanol and were subjected to histone deacetylase (HDAC) inhibition and toxicity studies...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142074/stat3-controls-col1a2-enhancer-activation-cooperatively-with-junb-regulates-type-i-collagen-synthesis-post-transcriptionally-and-is-essential-for-lung-myofibroblast-differentiation
#3
Ioannis Papaioannou, Shiwen Xu, Christopher P Denton, David J Abraham, Markella Ponticos
Fibroblast differentiation is key cellular process that underlies the process of fibrosis, a deadly complication of fibrotic diseases like Scleroderma (SSc). This transition coincides with the overproduction of Collagen type I (COL1) and other extracellular matrix proteins. High level expression of the collagen type 1α2 subunit (COL1A2), requires the engagement of a far upstream enhancer, whose activation is strongly dependent on the AP1 factor JunB. We now report that STAT3 also binds the COL1A2 enhancer and is essential for RNA polymerase recruitment, without affecting JunB binding...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29140794/targeted-elimination-of-senescent-ras-transformed-cells-by-suppression-of-mek-erk-pathway
#4
Elena Y Kochetkova, Galina I Blinova, Olga A Bystrova, Marina G Martynova, Valery A Pospelov, Tatiana V Pospelova
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras-transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition...
November 14, 2017: Aging
https://www.readbyqxmd.com/read/29138212/bax-inhibiting-peptide-attenuates-bleomycin-induced-lung-injury-in-mice
#5
Kunihiro Suzuki, Toyoshi Yanagihara, Tetsuya Yokoyama, Takashige Maeyama, Saiko Ogata-Suetsugu, Masako Arimura-Omori, Hironori Mikumo, Naoki Hamada, Eiji Harada, Kazuyoshi Kuwano, Taishi Harada, Yoichi Nakanishi
Rationale: Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.Objective: The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury...
November 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29138094/foxo1-3-potential-suppressors-of-fibrosis
#6
REVIEW
Zhenlong Xin, Zhiqiang Ma, Wei Hu, Shuai Jiang, Zhi Yang, Tian Li, Fulin Chen, Guozhan Jia, Yang Yang
Fibrosis is a universally age-related disease that involves nearly all organs. It is typically initiated by organic injury and eventually results in organ failure. There are still few effective therapeutic strategy targets for fibrogenesis. Forkhead box proteins O1 and O3 (FOXO1/3) have been shown to have favorable inhibitory effects on fibroblast activation and subsequent extracellular matrix production and can ameliorate fibrosis levels in numerous organs, including the heart, liver, lung, and kidney; they are therefore promising targets for anti-fibrosis therapy...
November 11, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29137334/the-coffee-diterpene-kahweol-enhances-sensitivity-to-sorafenib-in-human-renal-carcinoma-caki-cells-through-down-regulation-of-mcl-1-and-c-flip-expression
#7
Kyoung-Jin Min, Hee Jung Um, Jee In Kim, Taeg Kyu Kwon
Sorafenib is approved for the treatment of hepatocellular carcinoma (HCC) and advanced renal cell carcinoma (RCC). However, low tumor response and side effects have been widely reported. Therefore, to improve the efficacy of sorafenib, we investigated whether combined treatment with sorafenib and kahweol, the coffee-specific diterpene, has a synergistic effect on apoptotic cell death. Combined treatment with sorafenib and kahweol markedly induced caspase-mediated apoptosis in renal carcinoma Caki cells. Combined treatment with sorafenib and kahweol induced down-regulation of Mcl-1 and c-FLIP expression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133080/population-pharmacokinetics-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#8
Ulrike Schmid, Christiane Doege, Claudia Dallinger, Matthias Freiwald
BACKGROUND: Nintedanib is a potent intracellular inhibitor of tyrosine kinases, including the receptor kinases vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor. A previous model assessed the population pharmacokinetics of nintedanib and its main metabolite BIBF 1202 in patients with non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). The objective of this analysis was to further characterise the population pharmacokinetics of nintedanib in patients with IPF by including data from the Phase III trials...
November 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29133050/newly-designed-organotin-iv-carboxylates-with-peptide-linkage-synthesis-structural-elucidation-physicochemical-characterizations-and-pharmacological-investigations
#9
Muhammad Sirajuddin, Vickie McKee, Muhammad Tariq, Saqib Ali
Fourteen new organotin(IV) carboxylate complexes with peptide linkage of (2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid) were successfully synthesized and characterized by elemental analyses, FT-IR, NMR ((1)H, (13)C and (119)Sn) and single crystal X-ray techniques. FT-IR results of the sodium salt of 2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid and complexes showed that the coordination took place via oxygen atoms of the carboxylate group. (1)J((119)Sn-(13)C), (2)J((119)Sn-(1)H) and θ values calculated from (1)H and (13)C NMR data using Lockhart's equation reveal a trigonal bipyramidal geometry for triorganotin(IV) derivatives and an octahedral geometry for diorganotin(IV) derivatives...
November 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29133038/new-metalo-therapeutics-of-nsaids-against-human-breast-cancer-cells
#10
Christina N Banti, Constantina Papatriantafyllopoulou, Anastasios J Tasiopoulos, Sotiris K Hadjikakou
The non steroidal anti-inflammatory drugs (NSAID's)-silver(I) metallodrugs of aspirin (aspH), salicylic acid (salH2), naproxen (napH) acid or p-hydrobenzoic acid (pHbzaH) and the mitochondriotropic triphenylarsine (tpAs) with the formulae [Ag(asp)(tpAs)3] (1), [Ag(salH)(tpAs)3] (2), [Ag(nap)(tpAs)3] (3) and {[Ag(pHbza)(tpAs)3]∙(dmf)} (4) and [Ag(tpAs)3(NO3)] (5) have been synthesized and characterized by m.p., FT-IR, UV-vis and (1)H NMR, spectroscopic techniques and X-ray crystallography. The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer cells: MCF-7 (positive to estrogen receptors (ERs)) and MDA-MB-231 (negative to estrogen receptors (ERs)) was evaluated...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29131027/microrna-194-regulates-lipopolysaccharide-induced-cell-viability-by-inactivation-of-nuclear-factor-%C3%AE%C2%BA-b-pathway
#11
Fei Xie, Lei Yang, Lili Han, Bin Yue
The present study explored the functional role of microRNA (miR)-194 in lipopolysaccharide (LPS) induced lung cell injury, along with the underlying mechanisms and to reveal the potential role in infantile pneumonia. Human fibroblasts WI38 cells were transfected with miR-194 mimic or miR-194 inhibitor, and the transfection efficiency was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, the cells were treated with or without LPS, and then cell viability, cell apoptosis and mRNA and protein expressions of key proteins of nuclear factor kappa B (NF-κB) pathway including inhibitor of NF-κB (IκB) α, p-65, and B-cell CLL/lymphoma (Bcl) 3 were analyzed...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129520/f2-isoprostanes-can-mediate-bleomycin-induced-lung-fibrosis
#12
Beatrice Arezzini, Daniela Vecchio, Cinzia Signorini, Blerta Stringa, Concetta Gardi
F2-isoprostanes (F2-IsoPs) have been considered markers of oxidative stress in various pulmonary diseases, but little is known about their possible role in pulmonary fibrosis. In this study, we have investigated the potential key role of F2-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F2-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period. Lung F2-IsoP content nearly tripled 7 days following the intratracheal instillation of BLM, and by 28 days, the value increased about fivefold compared to the controls...
November 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29127199/the-full-length-interleukin-33-flil33-importin-5-interaction-does-not-regulate-flil33-s-nuclear-localization-but-controls-its-intracellular-degradation
#13
Andrew Clerman, Zahid Noor, Rita Fishelevich, Virginia Lockatell, Brian S Hampton, Nirav G Shah, Mariah V Salcedo, Nevins W Todd, Sergei P Atamas, Irina G Luzina
Human mature interleukin-33 (MIL33) is a member of the IL-1 family and a potent regulator of immunity through its pro-T helper cell 2 (Th2) activity. Its precursor form, full-length interleukin-33 (FLIL33), is an intranuclear protein in many cell types, including fibroblasts, and its intracellular levels can change in response to stimuli. However, the mechanisms controlling the nuclear localization of FLIL33 or its stability in cells are not understood. Here, we identified importin-5 (IPO5), a member of the importin family of nuclear transport proteins, as an intracellular binding partner of FLIL33...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29126429/rna-sequencing-analysis-of-lung-primary-fibroblast-response-to-eosinophil-degranulation-products-predicts-downstream-effects-on-inflammation-tissue-remodeling-and-lipid-metabolism
#14
Stephane Esnault, Ksenija Bernau, Elizabeth E Torr, Yury A Bochkov, Nizar N Jarjour, Nathan Sandbo
BACKGROUND: The association of eosinophils with inflammation and tissue remodeling is at least partially due to their release of toxic granule proteins and other mediators, including cytokines. Tissue remodeling and consequent functional defects are affected by activity of connective tissue fibroblasts. Exaggerated fibroblast activation, accumulation and change of phenotype may lead to fibrosis and loss of tissue function. So far, little information has been reported on how eosinophils affect inflammation and tissue remodeling via the activation of fibroblasts...
November 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29122847/human-airway-trypsin-like-protease-exerts-potent-antifibrotic-action-in-pulmonary-fibrosis
#15
Awen Menou, Pauline Flajolet, JanWillem Duitman, Aurélien Justet, Sophie Moog, Madeleine Jaillet, Laure Tabèze, Brigitte Solhonne, Marc Garnier, Hervé Mal, Pierre Mordant, Yves Castier, Aurélie Cazes, Jean-Michel Sallenave, Arnaud A Mailleux, Bruno Crestani
Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound-healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane-anchored serine protease human airway trypsin-like protease (HAT). In the present study, we show that both HAT expression and activity were up-regulated in human IPF specimens...
November 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29122839/fgf-receptors-control-alveolar-elastogenesis
#16
Rongbo Li, John C Herriges, Lin Chen, Robert P Mecham, Xin Sun
Alveologenesis is the final step of lung development characterized by the formation of millions of alveolar septa which constitute the vast gas-exchange surface area. The genetic network driving alveologenesis is poorly understood compared to those in earlier steps of lung development. Fibroblast Growth Factor (FGF) signaling through the FGF receptors, Fgfr3 and Fgfr4 (hereafter Fgfr3;4), is critical for alveologenesis. However, the mechanisms through which they mediate this process remain unclear. Here we show that in Fgfr3;4 global mutant mice, alveolar simplification is first observed at the onset of alveologenesis at postnatal day (P) 3...
November 9, 2017: Development
https://www.readbyqxmd.com/read/29121325/basic-fibroblast-growth-factor-protects-against-influenza-a-virus-induced-acute-lung-injury-by-recruiting-neutrophils
#17
Keyu Wang, Chengcai Lai, Tieling Li, Cheng Wang, Wei Wang, Bing Ni, Changqing Bai, Shaogeng Zhang, Lina Han, Hongjing Gu, Zhongpeng Zhao, Yueqiang Duan, Xiaolan Yang, Li Xing, Lingna Zhao, Shanshan Zhou, Min Xia, Chengyu Jiang, Xiliang Wang, Penghui Yang
Influenza virus (IAV) infection is a major cause of severe respiratory illness that affects almost every country in the world. IAV infections result in respiratory illness and even acute lung injury and death, but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated. In this study, the basic fibroblast growth factor 2 (FGF2) level was markedly increased in H1N1 virus-infected humans and mice. FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFκB signaling pathway...
November 7, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29118902/inhibitory-effects-of-thalidomide-on-bleomycin-induced-pulmonary-fibrosis-in-rats-via-regulation-of-thioredoxin-reductase-and-inflammations
#18
Xiaoying Dong, Xin Li, Minghui Li, Ming Chen, Qian Fan, Wei Wei
In this study, the potential clinical effects of thalidomide on bleomycin-induced pulmonary fibrosis were investigated. A Sprague-Dawley rats' model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin was adopted. The rats in thalidomide treated groups were intraperitoneally injected with thalidomide (10, 20, 50 mg/kg) daily for 28 days, while the rats in control and bleomycin treated groups were injected with a saline solution. The effects of thalidomide on pulmonary injury were evaluated by the lung wet/dry weight ratios, cell counts, and histopathological examination...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118338/sialidase-inhibitors-attenuate-pulmonary-fibrosis-in-a-mouse-model
#19
Tejas R Karhadkar, Darrell Pilling, Nehemiah Cox, Richard H Gomer
Fibrosis involves increasing amounts of scar tissue appearing in a tissue, but what drives this is unclear. In fibrotic lesions in human and mouse lungs, we found extensive desialylation of glycoconjugates, and upregulation of sialidases. The fibrosis-associated cytokine TGF-β1 upregulates sialidases in human airway epithelium cells, lung fibroblasts, and immune system cells. Conversely, addition of sialidases to human peripheral blood mononuclear cells induces accumulation of extracellular TGF-β1, forming what appears to be a sialidase - TGF-β1 - sialidase positive feedback loop...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116098/chemodrug-delivery-using-integrin-targeted-plga-chitosan-nanoparticle-for-lung-cancer-therapy
#20
Anish Babu, Narsireddy Amreddy, Ranganayaki Muralidharan, Gopal Pathuri, Hariprasad Gali, Allshine Chen, Yan D Zhao, Anupama Munshi, Rajagopal Ramesh
In this study, we report the efficacy of RGD (arginine-glycine-aspartic acid) peptide-modified polylactic acid-co-glycolic acid (PLGA)-Chitosan nanoparticle (CSNP) for integrin αvβ3 receptor targeted paclitaxel (PTX) delivery in lung cancer cells and its impact on normal cells. RGD peptide-modified chitosan was synthesized and then coated onto PTX-PLGA nanoparticles prepared by emulsion-solvent evaporation. PTX-PLGA-CSNP-RGD displayed favorable physicochemical properties for a targeted drug delivery system...
November 7, 2017: Scientific Reports
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