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https://www.readbyqxmd.com/read/29656465/structural-characterization-of-the-interaction-of-the-fibroblast-growth-factor-receptor-with-a-small-molecule-allosteric-inhibitor
#1
Franziska Kappert, Sridhar Sreeramulu, Hendrik R A Jonker, Christian Richter, Vladimir V Rogov, Ewgenij Proschak, Bruno Hargittay, Krishna Saxena, Harald Schwalbe
The interaction of fibroblast growth factors (FGFs) with their fibroblast growth factor receptors (FGFRs) are important in the signaling network of cell growth and development. SSR128129E (SSR)[1,2], a ligand of small molecular weight with potential anti-cancer properties, acts allosterically on the extracellular domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain of FGFR remained elusive. Here, we report the structural characterization of the interaction of SSR with one specific receptor, FGFR3 by NMR spectroscopy...
April 14, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29656442/treatment-emergent-hypertension-and-efficacy-in-the-phase-3-study-of-e7080-lenvatinib-in-differentiated-cancer-of-the-thyroid-select
#2
Lori J Wirth, Makoto Tahara, Bruce Robinson, Sanjeev Francis, Marcia S Brose, Mouhammed Amir Habra, Kate Newbold, Naomi Kiyota, Corina E Dutcus, Elton Mathias, Matthew Guo, Steven I Sherman, Martin Schlumberger
BACKGROUND: Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT)...
April 14, 2018: Cancer
https://www.readbyqxmd.com/read/29655920/suppressing-ku70-ku80-expression-elevates-homology-directed-repair-efficiency-in-primary-fibroblasts
#3
Guoling Li, Dewu Liu, Xianwei Zhang, Rong Quan, Cuili Zhong, Jianxin Mo, Yaoqiang Huang, Haoqiang Wang, Xiaofang Ruan, Zheng Xu, Enqin Zheng, Ting Gu, Linjun Hong, Zicong Li, Zhenfang Wu, Huaqiang Yang
The main DNA repair pathways, nonhomologous end joining (NHEJ) and homology-directed repair (HDR), are complementary to each other; hence, interruptions of the NHEJ pathway can favor HDR. Improving HDR efficiency in animal primary fibroblasts can facilitate the generation of gene knock-in animals with agricultural and biomedical values by somatic cell nuclear transfer. In this study, we used siRNA to suppress the expression of Ku70 and Ku80, which are the key factors in NHEJ pathway, to investigate the effect of Ku silencing on the HDR efficiency in pig fetal fibroblasts...
April 12, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29655846/telocyte-like-cells-containing-weibel-palade-bodies-in-rat-lamina-fusca
#4
C E Petrea, M C Rusu, V S Mănoiu, A D Vrapciu
Telocytes (TCs) are cells with long, thin and moniliform processes called telopodes. These cells have been found in numerous tissues, including the eye choroid and sclera. Lamina fusca (LF), an anatomical structure located at the sclera-choroid junction, has outer fibroblastic lamellae containing cells with long telopodes. The purpose of this study was to evaluate, via transmission electron microscopy, the LF for the presence of endothelial-specific ultrastructural features, such as Weibel-Palade bodies (WPBs), in the residing TCs...
April 12, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/29655694/tatanan-a-from-the-acorus-calamus-l-root-inhibited-dengue-virus-proliferation-and-infections
#5
Xingang Yao, Yun Ling, Songxin Guo, Wenyu Wu, Shijun He, Qing Zhang, Min Zou, Kutty Selva Nandakumar, Xiaoguang Chen, Shuwen Liu
BACKGROUND: Acorus calamus l. (Acoraceae) is a well-known traditional Chinese medicinal plant, whose root are historically mainly used to treat neurodegenerative diseases, and for cholera treatment. This datum strongly indicates the antimicrobial activity of A. calamus. PURPOSE: Our goal is to find the active constituents of A. calamus to treat dengue virus (DENV) infections, and to study the effects and mechanisms of these active substances. METHODS: The root of A...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655688/novel-ras-inhibitor-25-o-methylalisol-f-attenuates-epithelial-to-mesenchymal-transition-and-tubulo-interstitial-fibrosis-by-selectively-inhibiting-tgf-%C3%AE-mediated-smad3-phosphorylation
#6
Hua Chen, Tian Yang, Min-Chang Wang, Dan-Qian Chen, Yang Yang, Ying-Yong Zhao
BACKGROUND: Tubulo-interstitial fibrosis (TIF) is the common pathway in the chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) is a major contributor to the TIF by the increased myofibroblasts. Renin-angiotensin system (RAS) is critical mediator on EMT in progressive CKD. Angiotensin II (ANG) mediates EMT and causes TIF by stimulating transforming growth factor-β1 (TGF-β1). RAS activation could further activate TGF-β1. Inhibition of the RAS is one of the most powerful therapies for progressive CKD...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29653394/generation-of-duchenne-muscular-dystrophy-patient-specific-induced-pluripotent-stem-cell-line-lacking-exons-45-50-of-the-dystrophin-gene-iiti001-a
#7
Binyamin Eisen, Ronen Ben Jehuda, Ashley J Cuttitta, Lucy N Mekies, Irina Reiter, Sindhu Ramchandren, Michael Arad, Daniel E Michele, Ofer Binah
Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease caused by mutations in the dystrophin gene. We generated induced pluripotent stem cells (iPSCs) from a 13-year-old male patient carrying a deletion mutation of exons 45-50; iPSCs were subsequently differentiated into cardiomyocytes. iPSCs exhibit expression of the pluripotent markers (SOX2, NANOG, OCT4), differentiation capacity into the three germ layers, normal karyotype, genetic identity to the skin biopsy dermal fibroblasts and the patient-specific dystrophin mutation...
April 3, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29653380/fibroblast-populated-collagen-lattices-exhibit-opposite-biophysical-conditions-by-fibrin-or-hyaluronic-acid-supplementation
#8
Mario Chopin-Doroteo, Rosa M Salgado-Curiel, José Pérez-González, Benjamín M Marín-Santibáñez, Edgar Krötzsch
Fibrin and hyaluronic acid are important components of the provisional wound matrix. Through interactions with fibroblasts, they provide biophysical cues that regulate the viscoelastic properties of the extracellular matrix. To understand the roles of fibrin and hyaluronic acid in a collagenous environment, we used fibroblast populated collagen lattices (collagen, collagen-fibrin, and collagen-hyaluronic acid). Compared with collagen and collagen-hyaluronic acid cultures, collagen-fibrin cultures showed less contraction, which is correlated with increased elastic (G') and complex (|G*|) moduli, and reduced proportions of dendritic fibroblasts, despite increased αv integrin expression...
March 31, 2018: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29653196/transcription-factors-in-regulatory-and-protein-subnetworks-during-generation-of-neural-stem-cells-and-neurons-from-direct-reprogramming-of-non-fibroblastic-cell-sources
#9
Mohammad Reza Omrani, Moein Yaqubi, Abdulshakour Mohammadnia
Direct reprogramming of non-fibroblastic cells to the neuronal cell types including induced neurons (iNs) and induced neural stem cells (iNSCs) has provided an alternative approach for the direct reprogramming of fibroblasts to those cells. However, to increase the efficiency of the reprogramming process the underlaying mechanisms should be clarified. In the current study, we analyzed the gene expression profiles of five different cellular conversions to understand the most significant molecular mechanisms and transcription factors (TFs) underlying each conversion...
April 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29653185/sex-differences-in-the-development-of-hepatic-steatosis-in-cafeteria-diet-induced-obesity-in-young-mice
#10
Fabiana Rodrigues Silva Gasparin, Fernando Olinto Carreño, Juliana Moraes Mewes, Eduardo Hideo Gilglioni, Clairce Luzia Salgueiro Pagadigorria, Maria Raquel Marçal Natali, Karina Sayuri Utsunomiya, Rodrigo Polimeni Constantin, Amanda Tomie Ouchida, Carlos Curti, Ingrid C Gaemers, Ronald Petrus Johannes Oude Elferink, Jorgete Constantin, Emy Luiza Ishii-Iwamoto
The present study was planned to improve our understanding about sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar body weight gain and adiposity index, but FCaf had a more extensive steatosis than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease activity score, elevated lipid percentage area (+34%) in Sudan III staining and increased TG content (+25%) compared to MCaf...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29653143/phenotypic-characterization-of-the-sirc-statens-seruminstitut-rabbit-cornea-cell-line-reveals-a-mixed-epithelial-and-fibroblastic-nature
#11
Melania Olivieri, Martina Cristaldi, Salvatore Pezzino, Dario Rusciano, Barbara Tomasello, Carmelina Daniela Anfuso, Gabriella Lupo
The aim of the present study was to investigate, in the Statens Seruminstitut Rabbit Cornea (SIRC) cell line, the presence of epithelial and fibroblastic markers, comparing their levels with those of the human Retinal Pigmented Epithelial (ARPE-19) cell line, and the Human Keratocyte (HK) cell line, respectively. SIRC cells, often described as of epithelial origin, are used as a corneal epithelial barrier model to study the permeability of ophthalmic drugs. However, they show a morphology that is more consistent with a fibroblastic cell phenotype, similar to corneal keratocytes...
April 10, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29653141/dual-mechanism-of-type-vii-collagen-transfer-by-bone-marrow-mesenchymal-stem-cell-extracellular-vesicles-to-recessive-dystrophic-epidermolysis-bullosa-fibroblasts
#12
Jeffrey McBride, Luis Rodriguez-Menocal, Ambar Candanedo, Wellington Guzman, Marta Garcia-Contreras, Evangelos Badiavas
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease resulting from a lack of type VII collagen production. Recent clinical trials have shown efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the treatment of epidermolysis bullosa, including improved basement membrane restructuring and cutaneous wound healing. The mechanism as to how type VII collagen is transferred from donor stem cell to recipient RDEB cells has not been defined. Here, we submit the model that BM-MSC-derived extracellular vesicles serve at least two roles: 1) to help transport type VII collagen within the extracellular space; and 2) to feed RDEB fibroblasts with messenger RNA that codes for type VII collagen, resulting in COL7A1 translation and synthesis of type VII collagen alpha chain proteins by RDEB fibroblasts...
April 10, 2018: Biochimie
https://www.readbyqxmd.com/read/29653139/influence-of-zinc-oxide-quantum-dots-in-the-antibacterial-activity-and-cytotoxicity-of-an-experimental-adhesive-resin
#13
Isadora Martini Garcia, Vicente Castelo Branco Leitune, Fernanda Visioli, Susana Maria Werner Samuel, Fabrício Mezzomo Collares
OBJECTIVE: To evaluate the influence of zinc oxide quantum dots (ZnOQDs ) into an experimental adhesive resin regarding the antibacterial activity against Streptococcus mutans and the cytotoxicity against pulp fibroblasts. MATERIALS AND METHODS: ZnOQDs were synthesized by sol-gel process and were incorporated into 2-hydroxyethyl methacrylate (HEMA). An experimental adhesive resin was formulated by mixing 66.6 wt.% bisphenol A glycol dimethacrylate (BisGMA) and 33...
April 10, 2018: Journal of Dentistry
https://www.readbyqxmd.com/read/29653105/cst3-and-gdf15-ameliorate-renal-fibrosis-by-inhibiting-fibroblast-growth-and-activation
#14
Young-Im Kim, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
The final strategies to care patients with end-stage renal fibrosis rely on dialysis and kidney transplantation. Because such treatments are invasive and cause health problems eventually, it is necessary to develop new therapeutic strategies for delaying the disease progress. We here searched for cytokines showing an anti-fibrotic activity in cell-based experiments. Cystatin C (CST3) and Growth differentiation factor 15 (GDF15) were identified to have anti-fibrotic activities in a cytokine array screening. In primary fibroblasts isolated from the mouse kidneys subjected to ureteral obstruction-induced fibrosis, each cytokine induced apoptotic cell death and reduced collagen production...
April 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29653030/sex-modulates-the-association-of-fibroblast-growth-factor-21-with-end-stage-renal-disease-in-asian-people-with-type-2-diabetes-a-6-3-year-prospective-cohort-study
#15
Jian-Jun Liu, Sylvia Liu, Robin Wm Choo, Shiou Liang Wee, Aimin Xu, Su Chi Lim
AIM: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes. METHODS: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses...
April 13, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29652844/gga-mir-451-negatively-regulates-mycoplasma-gallisepticum-hs-strain-induced-inflammatory-cytokine-production-via-targeting-ywhaz
#16
Yabo Zhao, Kang Zhang, Mengyun Zou, Yingfei Sun, Xiuli Peng
Mycoplasma gallisepticum (MG) is the most economically significant mycoplasma pathogen of poultry that causes chronic respiratory disease (CRD) in chickens. Although miRNAs have been identified as a major regulator effect on inflammatory response, it is largely unclear how they regulate MG-induced inflammation. The aim of this study was to investigate the functional roles of gga-miR-451 and identify downstream targets regulated by gga-miR-451 in MG infection of chicken. We found that the expression of gga-miR-451 was significantly up-regulated during MG infection of chicken embryo fibroblast cells (DF-1) and chicken embryonic lungs...
April 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29652658/bcl-xl-and-mcl-1-upregulation-by-calreticulin-promotes-apoptosis-resistance-of-fibroblast-like-synoviocytes-via-activation-of-pi3k-akt-and-stat3-pathways-in-rheumatoid-arthritis
#17
Yachong Jiao, Hongmei Ding, Shanshan Huang, Yixin Liu, Xuguo Sun, Wei Wei, Jun Ma, Fang Zheng
OBJECTIVES: Fibroblast-like synoviocytes (FLS) play key roles in synovium hyperplasia and pannus formation in rheumatoid arthritis (RA). The present study was undertaken to explore the mechanisms that calreticulin (CRT) promoted anti-apoptosis of RA FLS. METHODS: The expression of CRT and anti-apoptotic proteins Bcl-XL and Mcl-1 in RA synovium were detected by immunohistochemistry. The expression of Bcl-XL and Mcl-1 in RA FLS by CRT were determined. The phosphorylation of Akt and STAT3 was detected by western blot...
April 13, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29652619/circulating-cytokine-chemokine-concentrations-respond-to-ionizing-radiation-doses-but-not-radiation-dose-rates-granulocyte-colony-stimulating-factor-and-interleukin-18
#18
Juliann G Kiang, Joan T Smith, Sara R Hegge, Natalia I Ossetrova
Exposure to ionizing radiation is a crucial life-threatening factor in nuclear and radiological incidents. It is known that ionizing radiation affects cytokine/chemokine concentrations in the blood of B6D2F1 mice. It is not clear whether radiation dose rates would vary the physiological response. Therefore, in this study we utilized data from two experiments using B6D2F1 female mice exposed to six different dose rates ranging from low to high rates. In one experiment, mice received a total dose of 8 Gy (LD0/30 ) of 60 Co gamma radiation at four dose rates: 0...
April 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29652546/ataxia-telangiectasia-mutated-kinase-deficiency-impairs-autophagic-response-early-during-myocardial-infarction
#19
Patsy R Thrasher, Stephanie L C Scofield, Suman Dalal, Claire C Crawford, Mahipal Singh, Krishna Singh
Ataxia-telangiectasia mutated kinase (ATM) is activated in response to DNA damage. We have previously shown that ATM plays a critical role in myocyte apoptosis and cardiac remodeling following myocardial infarction (MI). Here, we tested the hypothesis that ATM deficiency results in autophagic impairment in the heart early during MI. MI was induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery (LAD). Structural and biochemical parameters of the heart were measured 4 hours following LAD ligation...
April 13, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29652518/discoidin-domain-receptor-2-signaling-regulates-fibroblast-apoptosis-through-pdk1-akt
#20
Shijing Jia, Manisha Agarwal, Jibing Yang, Jeffrey C Horowitz, Eric S White, Kevin K Kim
Progressive fibrosis is a complication of many chronic diseases and collectively, organ fibrosis is the leading cause of death in the US. Fibrosis is characterized by accumulation of activated fibroblasts and excessive deposition of extracellular matrix proteins, especially type I collagen. Extensive research has supported a role for matrix signaling in propagating fibrosis but type I collagen itself is often considered an end product of fibrosis rather than an important regulator of continued collagen deposition...
April 13, 2018: American Journal of Respiratory Cell and Molecular Biology
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