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https://www.readbyqxmd.com/read/29791829/burosumab-therapy-in-children-with-x-linked-hypophosphatemia
#1
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/29789271/molecular-elements-in-fgf19-and-fgf21-defining-klb-fgfr-activity-and-specificity
#2
Archita Agrawal, Sebastian Parlee, Diego Perez-Tilve, Pengyun Li, Jia Pan, Piotr A Mroz, Ann Maria Kruse Hansen, Birgitte Andersen, Brian Finan, Alexei Kharitonenkov, Richard D DiMarchi
OBJECTIVE: To signal, FGF19 and FGF21 require co-receptor βKlotho (KLB) to act in concert with FGF receptors, and yet there is appreciable variance in the C-terminal sequences of these two novel metabolic hormones where binding is believed to be primary. We seek to determine the functional consequences for these amino acid differences and determine whether such information can be used to design high potency antagonists and agonists. METHODS: We employed a functional in vitro assay to identify C-terminal protein fragments capable of fully blocking KLB-mediated FGF19 and 21 receptor signaling...
May 11, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29786640/vitamin-d-in-vascular-calcification-a-double-edged-sword
#3
REVIEW
Jeffrey Wang, Jimmy J Zhou, Graham R Robertson, Vincent W Lee
Vascular calcification (VC) as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification...
May 22, 2018: Nutrients
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
#4
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/29784942/continuous-addition-of-progenitors-forms-the-cardiac-ventricle-in-zebrafish
#5
Anastasia Felker, Karin D Prummel, Anne M Merks, Michaela Mickoleit, Eline C Brombacher, Jan Huisken, Daniela Panáková, Christian Mosimann
The vertebrate heart develops from several progenitor lineages. After early-differentiating first heart field (FHF) progenitors form the linear heart tube, late-differentiating second heart field (SHF) progenitors extend the atrium and ventricle, and form inflow and outflow tracts (IFT/OFT). However, the position and migration of late-differentiating progenitors during heart formation remains unclear. Here, we track zebrafish heart development using transgenics based on the cardiopharyngeal gene tbx1. Live imaging uncovers a tbx1 reporter-expressing cell sheath that continuously disseminates from the lateral plate mesoderm towards the forming heart tube...
May 21, 2018: Nature Communications
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
#6
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 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777507/rankl-expression-is-increased-in-circulating-mononuclear-cells-of-patients-with-calcific-aortic-stenosis
#7
Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Roberta Buso, Massimo Puato, Mario Plebani, Martina Zaninotto, Davide Condotta, Giacomo Zoppellaro, Leopoldo Pagliani, Giuseppe Tarantini, Sabino Iliceto, Elisa Covolo, Giuseppe Faggian, Francesco Onorati, Mikhail Dodonov, Alessandro Daniotti, Paola Pantano, Zoran Olivari, Giovanni Benfari, Paolo Pauletto
We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0...
May 17, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29777011/fox-proteins-are-modular-competency-factors-for-facial-cartilage-and-tooth-specification
#8
Pengfei Xu, Bartosz Balczerski, Amanda Ciozda, Kristin Louie, Veronika Oralova, Ann Huysseune, J Gage Crump
Facial form depends on the precise positioning of cartilage, bone, and tooth fields in the embryonic pharyngeal arches. How complex signaling information is integrated to specify these cell types remains a mystery. We find that modular expression of Forkhead-domain transcription factors (Fox) in the zebrafish face arises through integration of Hh, Fgf, Bmp, Edn1, and Jagged-Notch pathways. Whereas loss of C-class Fox proteins results in reduced upper facial cartilages, loss of F-class Fox proteins results in distal jaw truncations and absent midline cartilages and teeth...
May 18, 2018: Development
https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#9
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29775757/molecular-characterization-of-physis-tissue-by-rna-sequencing
#10
Christopher R Paradise, Catalina Galeano-Garces, Daniela Galeano-Garces, Amel Dudakovic, Todd A Milbrandt, Daniel B F Saris, Aaron J Krych, Marcel Karperien, Gabriel B Ferguson, Denis Evseenko, Scott M Riester, Andre J van Wijnen, A Noelle Larson
The physis is a well-established and anatomically distinct cartilaginous structure that is crucial for normal long-bone development and growth. Abnormalities in physis function are linked to growth plate disorders and other pediatric musculoskeletal diseases. Understanding the molecular pathways operative in the physis may permit development of regenerative therapies to complement surgically-based procedures that are the current standard of care for growth plate disorders. Here, we performed next generation RNA sequencing on mRNA isolated from human physis and other skeletal tissues (e...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29771334/%C3%AE-catenin-activation-in-hair-follicle-dermal-stem-cells-induces-ectopic-hair-outgrowth-and-skin-fibrosis
#11
Yixin Tao, Qingchun Yang, Lei Wang, Jie Zhang, Xuming Zhu, Qianqian Sun, Yunbin Han, Qian Luo, Yushu Wang, Xizhi Guo, Ji Wu, Baojie Li, Xiao Yang, Lin He, Gang Ma
Hair follicle dermal sheath (DS) harbors hair follicle dermal stem cells (hfDSCs), which can be recruited to replenish DS and dermal papilla (DP). Cultured DS cells can differentiate into various cell lineages in vitro. However, it is unclear how its plasticity is modulated in vivo. Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration. Here we report that activation of β-catenin in DS generates ectopic HF outgrowth (EF) by reprogramming HF epidermal cells and DS cells themselves, and endows DS cells with hair inducing ability...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29770958/effects-of-massage-on-the-expression-of-proangiogenic-markers-in-rat-skin
#12
Katarzyna Ratajczak-Wielgomas, Krzysztof Kassolik, Jedrzej Grzegrzolka, Tomasz Halski, Aleksandra Piotrowska, Katarzyna Mieszala, Iwona Wilk, Marzenna Podhorska-Okolow, Piotr Dziegiel, Waldemar Andrzejewski
INTRODUCTION: Massage is a physiotherapeutic treatment, commonly used in both therapy and restoration of normal body functions. The aim of this work was to determine the effects of skin massage on stimulating the expression of angiogenesis-initiating factors, i.e. VEGF-A, FGF-2 (bFGF) and CD34 and on skin regeneration processes. MATERIAL AND METHODS: The study was conducted on 48 Buffalo strain rats, randomly divided into two groups. In the first group (M, the massaged group), massage was applied five times a week for 7 weeks...
May 17, 2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29770125/fgf23-actions-on-target-tissues-with-and-without-klotho
#13
REVIEW
Beatrice Richter, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769399/dissecting-and-culturing-animal-cap-explants
#14
Kevin S Dingwell, James C Smith
The animal cap explant is a simple but adaptable tool available to developmental biologists. The use of animal cap explants in demonstrating the presence of mesoderm-inducting activity in the Xenopus embryo vegetal pole is one of many elegant examples of their worth. Animal caps respond to a range of growth factors (e.g., Wnts, FGF, TGF-β), making them especially useful for studying signal transduction pathways and gene regulatory networks. Explants are also suitable for examining cell behavior and have provided key insights into the molecular mechanisms controlling vertebrate morphogenesis...
May 16, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29768539/evaluation-of-prophylactic-and-therapeutic-effects-of-sildenafil-on-acute-radiation-proctitis-in-rats
#15
Erkan Yavuz, Gulcin Ercan, Onur Olgac Karagulle, Busra Yaprak Bayrak, Aytac Biricik, Candas Ercetin, Berk Gokcek, Hakan Yigitbas, Ramazan Kusaslan, Atilla Celik, Osman Bilgin Gulcicek
PURPOSE: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). METHODS: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. RESULTS: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group...
April 2018: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29764921/fibroblast-growth-factor-23-and-risks-of-cardiovascular-and-noncardiovascular-diseases-a-meta-analysis
#16
Amarnath Marthi, Killian Donovan, Richard Haynes, David C Wheeler, Colin Baigent, Christopher M Rooney, Martin J Landray, Sharon M Moe, Jun Yang, Lisa Holland, Romina di Giuseppe, Annet Bouma-de Krijger, Borislava Mihaylova, William G Herrington
Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43-74 RU/ml and 38-47 pg/ml in 17 general population cohorts; 102-392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79-4212 RU/ml and 2526-5555 pg/ml in eight cohorts of patients on dialysis...
May 15, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29763898/fgfr4-links-glucose-metabolism-and-chemotherapy-resistance-in-breast-cancer
#17
Min Xu, Shuzheng Chen, Weibin Yang, Xue Cheng, Yani Ye, Jianting Mao, Xulu Wu, Li Huang, Jiansong Ji
BACKGROUND/AIMS: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. METHODS: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR)...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29758290/proteome-response-of-dental-pulp-cells-to-exogenous-fgf8
#18
Rozaliya Tsikandelova, Petko Mladenov, Sébastien Planchon, Silvia Kalenderova, Maria Dragneva, Zornitsa Mihaylova, Pavel Stanimirov, Vanyo Mitev, Jenny Renaut, Nikolay Ishkitiev
FGF8 specifies early tooth development by directing the migration of the early tooth founder cells to the site of tooth emergence. To date the effect of the FGF8 in adult dental pulp has not been studied. We have assessed the regenerative potential of FGF8 by evaluating changes in the proteome landscape of dental pulp following short- and long-term exposure to recombinant FGF8 protein. In addition, we carried out qRT PCR analysis to determine extracellular/adhesion gene marker expression and assessed cell proliferation and mineralization in response to FGF8 treatment...
May 11, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29754168/acromegaly-is-associated-with-high-fibroblast-growth-factor-21-levels
#19
B S Yurekli, N O Kutbay, M Aksit, A Suner, I Y Simsir, S Seckiner, G U Kocabas, G Bozkaya, F Saygili
PURPOSE: Fibroblast growth factor-21 (FGF-21) is a member of fibroblast growth factor family. Both growth hormone (GH) and FGF-21 take place in the regulation of glucose and lipid metabolism. We aimed to investigate FGF-21 levels in acromegaly which is characterized by excess GH levels and is associated with comorbidities and altered body composition. METHODS: We studied 43 subjects (21 females and 22 males, mean age of 50.0 ± 12.8) with acromegaly. The control group consisted of 40 gender- and age-matched subjects (25 females and 15 males, mean age of 48...
May 12, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29754009/dietary-nitrogen-and-calcium-modulate-cyp27b1-expression-in-young-goats
#20
M R Wilkens, K Elfers, M Schmicke, G Breves, A S Muscher-Banse
In livestock, feeding a reduced nitrogen (N) diet is favored for economic and ecological reasons. Ruminants cope more easily with a reduced N diet than monogastric species. However, changes in mineral homeostasis such as a reduction in 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ) concentrations, calcium (Ca), and IGF1 levels were observed in goats kept on a reduced N diet. The decrease in 1,25-(OH)2 D3 occurred even during a simultaneous reduction in dietary N and Ca, whereas a solitary Ca reduction stimulated 1,25-(OH)2 D3 synthesis...
April 3, 2018: Domestic Animal Endocrinology
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