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https://www.readbyqxmd.com/read/28813681/uncoupling-the-mitogenic-and-metabolic-functions-of-fgf1-by-tuning-fgf1-fgf-receptor-dimer-stability
#1
Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J Conklin, Thomas A Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1(ΔHBS)) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1(ΔHBS) exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#2
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28805978/obeticholic-acid-a-selective-farnesoid-x-receptor-agonist-regulates-bile-acid-homeostasis-in-sandwich-cultured-human-hepatocytes
#3
Yuanyuan Zhang, Jonathan P Jackson, Robert L St Claire, Kimberly Freeman, Kenneth R Brouwer, Jeffrey E Edwards
Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805233/analytic-and-dynamic-secretory-profile-of-patient-derived-cytokine-induced-killer-cells
#4
Giulia Mesiano, Roberta Zini, Giulia Montagner, Nicoletta Bianchi, Rossella Manfredini, Antonella Chillemi, Massimo Aglietta, Giovanni Grignani, Ilaria Lampronti, Erika Fiorino, Fabio Malavasi, Dario Sangiolo, Roberto Gambari, Davide Ferrari
Adoptive immunotherapy with Cytokine Induced Killer (CIK) cells has shown antitumor activity against several kinds of cancers in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHC-unrestricted antitumor activity. Literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points (day 1, day 14 and day 21) of CIK cells expansion...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28804438/green-tea-extract-induces-genes-related-to-browning-of-white-adipose-tissue-and-limits-weight-gain-in-high-energy-diet-fed-rat
#5
Li-Han Chen, Yi-Wen Chien, Chung-Tiang Liang, Ching-Hung Chan, Meng-Han Fan, Hui-Yu Huang
Background: A wealth of research has reported on the anti-obesity effects of green tea extract (GTE). Although browning of white adipose tissue (WAT) has been reported to attenuate obesity, no study has disclosed the effects of GTE on browning in Sprague Dawley rats. Objectives: The aims of the study were to investigate the effects of GTE on anti-obesity and browning, and their underlying mechanisms. Methods: Four groups of rats (n=10/group) were used including a normal diet with vehicle treatment, and a high-energy diet (HED) with vehicle or GTE by oral gavage at 77...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28803689/sun-exposure-influences-the-prognostic-power-of-components-of-mineral-metabolism-in-patients-with-coronary-artery-disease
#6
A Aceña, J A Franco-Peláez, C Gutierrez-Landaluce, A M Pello, C Cristóbal, N Tarín, A Huelmos, R Carda, M L Martín-Mariscal, J Alonso, E González-Parra, M L González-Casaus, Ó Lorenzo, L López Bescos, J Egido, J Tuñón
BACKGROUND AND AIM: Calcidiol (vitamin D metabolite) plasma levels vary with sun exposure (SE). However, it is not known if SE influences its prognostic ability. We have studied the effect of SE on plasma levels of the components of mineral metabolism (calcidiol, fibroblast growth factor-23 [FGF-23], parathormone [PTH], and phosphate [P]) and on their prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: We studied prospectively 704 patients with stable CAD...
June 15, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28797724/the-effect-of-newly-synthesized-progesterone-derivatives-on-apoptotic-and-angiogenic-pathway-in-mcf-7-breast-cancer-cells
#7
Shaymaa M M Yahya, Abdou O Abdelhamid, Mervat M Abd-Elhalim, Ghada H Elsayed, Emad F Eskander
Due to its high potency and selectivity, anticancer agents consisting of combined molecules have gained great interests. The current study introduces newly synthesized progesterone derivatives of promising anticancer effect. Moreover, the pro-apoptotic and anti-angiogenic effects of these compounds were studied extensively. Several thiazole, pyridine, pyrazole, thiazolopyridine and pyrazolopyridine progesterone derivatives were synthesized. The structure of the novel progesterone derivatives was elucidated and confirmed using the analytical and spectral data...
August 8, 2017: Steroids
https://www.readbyqxmd.com/read/28792535/occurrence-and-severity-of-non-occlusive-mesenteric-ischemia-nomi-after-cardiovascular-surgery-correlate-with-preoperatively-assessed-fgf-23-levels
#8
Jonas Stroeder, Matthias Klingele, Hagen Bomberg, Stefan Wagenpfeil, Arno Buecker, Hans-Joachim Schaefers, Marcus Katoh, Peter Minko
PURPOSE: To evaluate the value of preoperatively assessed fibroblast growth factor 23 (FGF-23) levels and to correlate FGF-23 with angiographic findings in non-occlusive mesenteric (NOMI) ischemia using a standardized scoring system. MATERIALS AND METHODS: Between 2/2011 and 3/2012 a total of 865 patients (median age: 67 years) underwent cardiovascular surgery during this ethics committee approved, prospective study. 65 of these patients had clinical suspicion of NOMI and consequently underwent catheter angiography of the superior mesenteric artery...
2017: PloS One
https://www.readbyqxmd.com/read/28792088/the-anti-proliferation-effects-of-oleanolic-acid-on-a7r5-cells-role-of-ucp2-and-downstream-fgf-2-p53-tsp-1
#9
Yantao Han, Qixiao Jiang, Yu Wang, Wenqian Li, Min Geng, Zhiwu Han, Xuehong Chen
Vascular smooth muscle cell (VSMC) proliferation is a major contributor to atherosclerosis. This study investigated the inhibitatory effects of oleanolic acid (OA) against oxidized low density lipoprotein (ox-LDL) induced VSMC proliferation in A7r5 cells and explored underlying molecular mechanism. The cell proliferation was quantified with cell counting kit-8 (CCK-8), in which ox-LDL significantly increased A7r5 cells proliferation, while OA pretreatment effectively alleviated such changes without inducing overt cytotoxicity, as indicated by lactate dehydrogenase (LDH) assay...
August 9, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28791365/fgf8-promotes-cell-proliferation-and-resistance-to-egfr-inhibitors-via-upregulation-of-egfr-in-human-hepatocellular-carcinoma-cells
#10
Yuanmin Pei, Xueling Sun, Xiwei Guo, Huashan Yin, Le Wang, Fugu Tian, Hongxi Jing, Xiaobo Liang, Jun Xu, Pengcheng Shi
Fibroblast growth factor 8 (FGF8), a member of the fibroblast growth factor (FGF) family, is upregulated in several human cancers, including HCC (HCC). Previous studies have demonstrated that FGF8 increased cell growth and invasion of tumor cells. In the present study we investigated whether FGF8 is involved in the cell proliferation and resistance to several drugs in human HCC cells. We stably overexpressed FGF8 by lentiviral transfection. In addition, we also added recombinant FGF8 instead of stably overexpressing FGF8 in human HCC cells...
August 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28791357/synergistic-effects-of-fibroblast-growth-factor-2-and-bone-morphogenetic-protein-2-on-bone-induction
#11
Rongying Song, Dingding Wang, Rong Zeng, Ju Wang
The present study investigated the synergistic effect of co‑administering fibroblast growth factor‑2 (FGF‑2) and bone morphogenetic protein‑2 (BMP‑2) on osteoblastic differentiation in C2C12 cells and in rats. C2C12 murine myoblast cells represent a well‑accepted in vitro model system to study the ability of BMP‑2 to alter cell lineage from the myogenic to the osteogenic phenotype. The osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) and Alizarin red S staining...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28781254/-fibroblast-growth-factors-and-their-effects-in-pancreas-organogenesis
#12
REVIEW
D A Gnatenko, E P Kopantzev, E D Sverdlov
Fibroblast growth factors (FGF) - growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we will summarize current information about the involvement of FGFs in the pancreas organogenesis. Pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue. This orchestrates the activation of various regulator genes at specific stages, determining the specification of progenitor cells...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28774557/fibroblast-growth-factor-21-plays-an-inhibitory-role-in-vascular-calcification-in-vitro-through-opg-rankl-system
#13
Fangying Cao, Xiaoxiao Liu, Xiangrong Cao, Shaoping Wang, Kun Fu, Yejing Zhao, Fang Shen, Jinghua Liu
Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased...
July 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28771625/inhibition-of-dipeptidyl-peptidase-4-ameliorates-cardiac-ischemia-and-systolic-dysfunction-by-up-regulating-the-fgf-2-egr-1-pathway
#14
Masayoshi Suda, Ippei Shimizu, Yohko Yoshida, Yuka Hayashi, Ryutaro Ikegami, Goro Katsuumi, Takayuki Wakasugi, Yutaka Yoshida, Shujiro Okuda, Tomoyoshi Soga, Tohru Minamino
Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine...
2017: PloS One
https://www.readbyqxmd.com/read/28768168/what-s-so-special-about-fgf19-unique-effects-reported-on-skeletal-muscle-mass-and-function
#15
David J Glass
In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective.
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28765932/fgf18-inhibits-mc3t3%C3%A2-e1-cell-osteogenic-differentiation-via-the-erk-signaling-pathway
#16
Feng Zhai, Na Song, Jisheng Ma, Weiyue Gong, Haishan Tian, Xiaokun Li, Chao Jiang, Haijun Wang
Fibroblast growth factor (FGF) 18 is a member of the FGF family and serves a key role in skeletal growth and development. The present study investigated the effect of FGF18 on pre‑osteoblast MC3T3-E1 cells and the signaling pathways involved by performing an alkaline phosphatase (ALP) assay and reverse transcription‑quantitative polymerase chain reaction. MC3T3‑E1 cells incubated in a culture medium supplemented with FGF18 exhibited increased viability when compared with the untreated control cells. In addition, ALP activity was decreased in MC3T3‑E1 cells treated with FGF18 plus an osteogenic medium (OM) for 7 and 14 days when compared with untreated and OM‑treated controls...
July 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28760345/dynamics-of-actinotrichia-regeneration-in-the-adult-zebrafish-fin
#17
Désirée König, Lionel Page, Bérénice Chassot, Anna Jaźwińska
The skeleton of adult zebrafish fins comprises lepidotrichia, which are dermal bones of the rays, and actinotrichia, which are non-mineralized spicules at the distal margin of the appendage. Little is known about the regenerative dynamics of the actinotrichia-specific structural proteins called Actinodins. Here, we used immunofluorescence analysis to determine the contribution of two paralogous Actinodin proteins, And1/2, in regenerating fins. Both proteins were detected in the secretory organelles in the mesenchymal cells of the blastema, but only And1 was detected in the epithelial cells of the wound epithelium...
July 29, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28759185/serum-fgf21-in-girls-with-anorexia-nervosa-comparison-to-normal-weight-and-obese-female-adolescents
#18
(no author information available yet)
BACKGROUND: Fibroblast growth factor 21 (FGF21) is a hepatokine, myokine and adipokine of a potent influence to energy homeostasis. Data according its serum concentrations in AN are contradictory. OBJECTIVES: Analysis of serum FGF21 in girls with acute anorexia nervosa and comparison the results with normal weight and obese female adolescents considering their nutritional status, carbohydrate and lipid metabolism. METHODS: Serum FGF21 concentrations were evaluated using commercially available ELISA kit in 32 Polish girls with restrictive AN (AN), 29 girls with obesity (O) and 21 healthy controls (C)...
July 31, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28757146/regulation-of-receptor-binding-specificity-of-fgf9-by-an-autoinhibitory-homodimerization
#19
Yang Liu, Jinghong Ma, Andrew Beenken, Lakshmi Srinivasan, Anna V Eliseenkova, Moosa Mohammadi
The epithelial fibroblast growth factor 9 (FGF9) subfamily specifically binds and activates the mesenchymal "c" splice isoform of FGF receptors 1-3 (FGFR1-3) to regulate organogenesis and tissue homeostasis. The unique N and C termini of FGF9 subfamily ligands mediate a reversible homodimerization that occludes major receptor binding sites within the ligand core region. Here we provide compelling X-ray crystallographic, biophysical, and biochemical data showing that homodimerization controls receptor binding specificity of the FGF9 subfamily by keeping the concentration of active FGF9 monomers at a level, which is sufficient for a normal FGFR "c" isoform binding/signaling, but is insufficient for an illegitimate FGFR "b" isoform binding/signaling...
July 11, 2017: Structure
https://www.readbyqxmd.com/read/28756207/pregnane-x-receptor-pxr-deficiency-improves-high-fat-diet-induced-obesity-via-induction-of-fibroblast-growth-factor-15-fgf15-expression
#20
Li-Yang Zhao, Jia-Yi Xu, Zhe Shi, Neal A Englert, Shu-Yun Zhang
Obesity has become a significant global health problem, and is a high risk factor for a variety of metabolic diseases. Fibroblast growth factor (FGF) 15 plays an important role in the regulation of metabolism. Xenobiotic-sensing nuclear receptors pregnane X receptor (PXR/NR1I2) and constitutive androstane receptor (CAR/NR1I3) play important roles in xenobiotic detoxification and metabolism, and also are involved in the regulation of energy metabolism. However, the effects that PXR and CAR have on the regulation of FGF15 are unknown...
July 26, 2017: Biochemical Pharmacology
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