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https://www.readbyqxmd.com/read/29791829/burosumab-therapy-in-children-with-x-linked-hypophosphatemia
#1
RANDOMIZED CONTROLLED TRIAL
Thomas O Carpenter, Michael P Whyte, Erik A Imel, Annemieke M Boot, Wolfgang Högler, Agnès Linglart, Raja Padidela, William Van't Hoff, Meng Mao, Chao-Yin Chen, Alison Skrinar, Emil Kakkis, Javier San Martin, Anthony A Portale
BACKGROUND: X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. METHODS: In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range...
May 24, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29785126/impact-of-targeting-transforming-growth-factor-%C3%AE-2-with-antisense-ot-101-on-the-cytokine-and-chemokine-profile-in-patients-with-advanced-pancreatic-cancer
#2
Osmond J D'Cruz, Sanjive Qazi, Larn Hwang, Kevin Ng, Vuong Trieu
Background: Overexpression of the cytokine - transforming growth factor-beta 2 (TGF-β2) - has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-β2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-β receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29778534/fibroblast-growth-factor-19-protects-the-heart-from-oxidative-stress-induced-diabetic-cardiomyopathy-via-activation-of-ampk-nrf2-ho-1-pathway
#3
Xin Li, Di Wu, Ye Tian
Diabetes affects cardiac structure and function, where it leads to diabetic cardiomyopathy. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of diabetic cardiomyopathy. Fibroblast growth factor (FGF) 19, an enterokine, is synthesized and released into the ileum. In the present study, we revealed that FGF19 induced an antioxidant response through stimulating the expression of nuclear erythroid factor 2 (NE-F2)-related factor 2 (Nrf2) and as well as reducing ROS production through the AMPK signaling pathway...
May 23, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29734515/decreased-placental-and-muscular-expression-of-the-fibroblast-growth-factor-19-in-gestational-diabetes-mellitus
#4
Dongyu Wang, Shuqia Xu, Wenjing Ding, Caixia Zhu, Songqing Deng, Xiwen Qiu, Zilian Wang
AIMS: Fibroblast growth factor (FGF) 19 has been shown to improve glycaemic homeostasis and lipid metabolism in animal models. In humans, decreased FGF19 level has been described in diabetes. This study aimed to investigate the expression of FGF19 in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Samples for measurement were obtained from 20 GDM women and 25 healthy controls. The mRNA and protein expression levels of FGF19, FGF21 and co-receptor β-klotho (KLB) in placenta, rectus muscle and subcutaneous fat tissues were quantified by real-time quantitative polymerase chain reaction, western-blot and immunohistochemistry, respectively...
May 7, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29621752/fibroblast-growth-factor-23-a-biomarker-of-kidney-function-decline
#5
David A Drew, Ronit Katz, Stephen Kritchevsky, Joachim H Ix, Michael G Shlipak, Anne B Newman, Andy Hoofnagle, Linda Fried, Mark J Sarnak, Orlando M Gutierrez
BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. METHODS: Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults...
2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29574933/the-association-of-serum-fgf23-and-non-alcoholic-fatty-liver-disease-is-independent-of-vitamin-d-in-type-2-diabetes-patients
#6
Xingxing He, Yun Shen, Xiaojing Ma, Lingwen Ying, Jiahui Peng, Xiaoping Pan, Yuqian Bao, Jian Zhou
Recent studies have shown that circulating fibroblast growth factor (FGF) 23 and vitamin D levels are closely correlated with insulin resistance. The aim of this study was to investigate the relationship among serum FGF 23 levels, serum 25-hydroxyvitamin D [25(OH)D] levels, and non-alcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This study enrolled 331 hospitalized T2DM patients (209 patients with NAFLD and 122 patients without NAFLD). Serum FGF23 levels were measured using a sandwich enzyme-linked immunosorbent assay...
March 25, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29558905/novel-biomarker-based-model-for-the-prediction-of-sorafenib-response-and-overall-survival-in-advanced-hepatocellular-carcinoma-a-prospective-cohort-study
#7
Hwi Young Kim, Dong Hyeon Lee, Jeong-Hoon Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
BACKGROUND: Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). METHODS: This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib...
March 20, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29549243/effects-of-supplemented-isoenergetic-diets-varying-in-cereal-fiber-and-protein-content-on-the-bile-acid-metabolic-signature-and-relation-to-insulin-resistance
#8
Martin O Weickert, John G Hattersley, Ioannis Kyrou, Ayman M Arafat, Natalia Rudovich, Michael Roden, Peter Nowotny, Christian von Loeffelholz, Silke Matysik, Gerd Schmitz, Andreas F H Pfeiffer
Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX)...
March 7, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29519501/fgf-19-agonism-for-nash-a-short-study-of-a-long-disease
#9
Michael Charlton
No abstract text is available yet for this article.
March 24, 2018: Lancet
https://www.readbyqxmd.com/read/29468415/the-ileal-fgf15-19-to-hepatic-fgfr4-axis-regulates-liver-regeneration-after-partial-hepatectomy-in-mice
#10
Qiang Li, Qiang Zhao, Chuanzhao Zhang, Peng Zhang, Anbin Hu, Longjuan Zhang, Paul M Schroder, Yi Ma, Zhiyong Guo, Xiaofeng Zhu, Xiaoshun He
Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling...
February 22, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29467286/viral-insulin-like-peptides-activate-human-insulin-and-igf-1-receptor-signaling-a-paradigm-shift-for-host-microbe-interactions
#11
Emrah Altindis, Weikang Cai, Masaji Sakaguchi, Fa Zhang, Wang GuoXiao, Fa Liu, Pierre De Meyts, Vasily Gelfanov, Hui Pan, Richard DiMarchi, C Ronald Kahn
Viruses are the most abundant biological entities and carry a wide variety of genetic material, including the ability to encode host-like proteins. Here we show that viruses carry sequences with significant homology to several human peptide hormones including insulin, insulin-like growth factors (IGF)-1 and -2, FGF-19 and -21, endothelin-1, inhibin, adiponectin, and resistin. Among the strongest homologies were those for four viral insulin/IGF-1-like peptides (VILPs), each encoded by a different member of the family Iridoviridae VILPs show up to 50% homology to human insulin/IGF-1, contain all critical cysteine residues, and are predicted to form similar 3D structures...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29409758/regulation-of-natriuretic-peptides-postprandially-in-vivo-and-of-their-receptors-in-adipocytes-by-fatty-acids-in-vitro
#12
Andreas Schmid, Jens Albrecht, Judith Brock, Maria Koukou, Efthymia Arapogianni, Andreas Schäffler, Thomas Karrasch
BACKGROUND AND AIM: Natriuretic peptides (NPs) and their receptors gain attention regarding adipocyte function. It was the aim to investigate the expression of natriuretic peptide receptors NPR-A, NPR-B and NPR-C during adipocyte differentiation (AD), upon stimulation with fatty acids (FA), and in murine and human adipose tissue depots (AT) of patients undergoing bariatric surgery (n = 44). PATIENTS, MATERIAL AND METHODS: The postprandial regulation of NT-proANP and NT-proBNP levels was measured by ELISA and was studied in two cohorts of healthy individuals undergoing an oral glucose tolerance test (OGTT) (n = 100) and an oral lipid tolerance test (OLTT) (n = 100)...
January 31, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29376143/bevacizumab-injection-in-patients-with-neovascular-age-related-macular-degeneration-increases-angiogenic-biomarkers
#13
Thiago Cabral, Luiz H Lima, Luiz Guilherme M Mello, Júlia Polido, Éverton P Correa, Akiyoshi Oshima, Jimmy Duong, Pedro Serracarbassa, Caio V Regatieri, Vinit B Mahajan, Rubens Belfort
Purpose: To evaluate the expression of 19 angiogenic biomarkers in the aqueous humor before and after intravitreal bevacizumab injection (IVB) in eyes with neovascular age-related macular degeneration (AMD). Design: Prospective, noncomparative, interventional case series. Participants: Twenty-three eyes of 23 treatment-naïve patients with choroidal neovascularization (CNV) secondary to neovascular AMD. Methods: Eyes were diagnosed with CNV secondary to neovascular AMD and were treated with 3 monthly IVBs...
January 2018: Ophthalmology Retina
https://www.readbyqxmd.com/read/29367522/low-plasma-levels-of-fibroblast-growth-factor-21-in-patients-with-peripheral-artery-disease
#14
Yoshichika Miyazaki, Emi Saita, Yoshimi Kishimoto, Susumu Ibe, Toshiki Seki, Kotaro Miura, Norie Suzuki-Sugihara, Yukinori Ikegami, Reiko Ohmori, Kazuo Kondo, Yukihiko Momiyama
AIM: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated. METHODS: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening...
January 24, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29325128/relationship-between-12-adipocytokines-and-distinct-components-of-the-metabolic-syndrome
#15
Thomas Ebert, Claudia Gebhardt, Markus Scholz, Tobias Wohland, Dorit Schleinitz, Mathias Fasshauer, Matthias Blüher, Michael Stumvoll, Peter Kovacs, Anke Tönjes
Objective: Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related to metabolic and cardiovascular traits, it is unknown which adipocytokine or adipocytokine clusters serve as meaningful markers of metabolic syndrome (MS) components. Therefore, this study investigated the associations of 12 adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29226620/comparative-potency-of-obeticholic-acid-and-natural-bile-acids-on-fxr-in-hepatic-and-intestinal-in-vitro-cell-models
#16
Yuanyuan Zhang, Carl LaCerte, Sanjay Kansra, Jonathan P Jackson, Kenneth R Brouwer, Jeffrey E Edwards
Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR-mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich-cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29190740/correlation-of-serum-cytokines-chemokines-growth-factors-and-enzymes-with-periodontal-disease-parameters
#17
Jeneen Panezai, Ambereen Ghaffar, Mohammad Altamash, Karl-Gösta Sundqvist, Per-Erik Engström, Anders Larsson
BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects. MATERIALS & METHODS: Periodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14)...
2017: PloS One
https://www.readbyqxmd.com/read/29174027/association-of-serum-fibroblast-growth-factor-19-levels-with-visceral-fat-accumulation-is-independent-of-glucose-tolerance-status
#18
X Hu, Q Xiong, Y Xu, X Zhang, X Pan, X Ma, Y Bao, W Jia
BACKGROUND AND AIMS: Recent studies suggested that circulating fibroblast growth factor (FGF) 19 levels might be associated with the fat content and distribution, and varied with different glucose tolerance status. This study aimed to investigate the association of serum FGF19 levels with obesity and visceral fat accumulation in a Chinese population with differing glucose tolerance status. METHODS AND RESULTS: The 2383 participants were divided into subgroups of glucose tolerance status: normal glucose tolerance (NGT, n = 1754), impaired glucose regulation (IGR, n = 499), and newly diagnosed diabetes mellitus (DM, n = 130)...
February 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29102744/modulating-bile-acid-pathways-and-tgr5-receptors-for-treating-liver-and-gi-diseases
#19
REVIEW
Harmeet Malhi, Michael Camilleri
Bile acids are central signals in enterohepatic communication and also integrate microbiota-derived signals into this signaling axis. Discovery of the tissue distribution and signaling pathways activated by the natural receptors for bile acids, farnesoid X receptor and G protein-coupled bile acid receptor 1 (GPBAR1) also known as TGR5, and bile acid transporters has led to the development of therapeutic agents that target these molecules. Obeticholic acid, a selective FXR agonist, and NGM282, a non-mitogenic FGF-19 analog, are two of the agents in this pipeline...
December 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29096734/endocrine-adiponectin-fgf15-19-axis-in-ethanol-induced-inflammation-and-alcoholic-liver-injury
#20
Min You, Zhou Zhou, Michael Daniels, Alvin Jogasuria
Alcoholic liver disease (ALD) is the most prevalent form of liver diseases, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades and exert similar beneficial functions...
November 2, 2017: Gene Expression
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