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Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
Hamit Yasar Ellidag, Necat Yilmaz, Fatma Kurtulus, Ozgur Aydin, Esin Eren, Ayca Inci, Suleyman Dolu, Fatma Demet Arslan Ince, Özlem Giray, Aylin Yaman
BACKGROUND: The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP). PURPOSE: This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients. METHODS: Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38...
September 2016: Annals of Neurosciences
Bas C J Majoor, Natasha M Appelman-Dijkstra, M Fiocco, Michiel A J van de Sande, P D Sander Dijkstra, Neveen A T Hamdy
INTRODUCTION: McCune-Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies and café-au-lait patches. FD patients have been shown to respond favourably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long-term. METHODS: We evaluated the biochemical (bone turnover markers; BTMs) and clinical (pain reduction) outcome of bisphosphonate therapy in eleven patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range 2-25)...
September 20, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Zhouzheng Ren, Daniel E Bütz, Jordan M Sand, Mark E Cook
Novel means to reduce phosphate input into poultry feeds and increase its retention would preserve world phosphate reserves and reduce environmental impact of poultry production. Here we show that a maternally derived antibody to a fibroblast growth factor-23 (FGF-23) peptide (GMNPPPYS) alleviated phosphorus deficiency in chicks fed low non-phytate phosphorus (nPP) diets. White Leghorn laying hens were vaccinated with either an adjuvant control or the synthetic FGF-23 peptide, and chicks with control or anti-FGF-23 maternal antibodies were fed a diet containing either 0...
September 19, 2016: Poultry Science
Sukka Santosh Reddy, Parul Chauhan, Preeti Maurya, Deepika Saini, Prem Prakash Yadav, Manoj Kumar Barthwal
Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide...
October 15, 2016: Toxicology and Applied Pharmacology
Donal J Sexton, M W O'Reilly, P Geoghegan, S M Kinsella, P J Moran, A W O'Regan
BACKGROUND: Serum fibroblastic growth factor (FGF) 23 has recently been established as a major physiological regulator of phosphate homeostasis and may have a causal role in adverse cardiovascular and bone outcomes. However its role in states of disordered phosphate homeostasis and normal kidney function is as yet under characterised. AIMS: To investigate whether this biomarker of vascular calcification and adverse bone outcomes is detectable in patients with sarcoidosis...
2016: Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG
A Zittermann, J B Ernst
AIMS: Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH)2D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non-pharmacological measures for targeting these hormones. DATA SYNTHESIS: The role of 1,25(OH)2D in the regulation of calcium and phosphate homeostasis is central...
June 28, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Sanae Ito, Hiromi Ishida, Kazuhiro Uenishi
Phosphorus homeostasis is determined by dietary intake, intestinal absorption, and renal tubular reabsorption of phosphorus. Serum fibroblast growth factor-23 (FGF-23) is considered to be a sensitive early biomarker of disordered phosphorus metabolism in both patients with chronic kidney diseases and healthy subjects. However, the number of studies evaluating serum FGF-23 concentrations in healthy subjects is limited. The objective of this cross-sectional study was to examine the relationship between serum FGF-23 concentrations and phosphorus related factors in 182 young Japanese women (mean age, 19...
2016: Asia Pacific Journal of Clinical Nutrition
Ge Song, Xiao-Xia Shao, Qing-Ping Wu, Zeng-Guang Xu, Ya-Li Liu, Zhan-Yun Guo
We recently developed novel bioluminescent binding assays for several protein/peptide hormones to study their interactions with receptors using the so far brightest NanoLuc reporter. To validate the novel bioluminescent binding assay using a variety of protein/peptide hormones, in the present work we applied it to the fibroblast growth factor (FGF) family using the prototype member FGF2 as an example. A fully active recombinant FGF2 retaining a unique exposed cysteine (Cys) residue was chemically conjugated with an engineered NanoLuc carrying a unique exposed Cys residue at the C-terminus via formation of an intermolecular disulfide linkage...
2016: PloS One
E Du, L Xiao, M M Hurley
High molecular weight FGF2 transgenic mice (HMWTg) phenocopy the Hyp mouse, homolog of human X-linked hypophosphatemic rickets with phosphate wasting and abnormal fibroblast growth factor (FGF23), fibroblast growth factor receptor (FGFR), Klotho and mitogen activated protein kinases (MAPK) signaling in kidney. In this study, we assessed whether short-term (24 h) in vivo administration of FGF23 neutralizing antibody (FGF23Ab) could rescue hypophosphatemia and impaired FGFR signaling in kidneys of HMWTg male mice...
June 16, 2016: Journal of Cellular Physiology
Diana R Mager, Stephanie T Jackson, Michelle R Hoffmann, Kailash Jindal, Peter A Senior
BACKGROUND: Adults with diabetes (DM) and chronic kidney disease (CKD) are at risk for vitamin D (vitD) insufficiency, suboptimal bone health and reduced quality of life (QoL) due to limited sunlight exposure, poor vitD intake and CKD. AIMS: This open-labeled, randomized clinical trial, compared the impact of daily (2000 IU/D) verses monthly (40,000 IU/month) vitD3 supplementation over six months on markers of vitD status, bone health and QoL in adults with DM and CKD (stages: 1-4)...
June 2, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Kimitaka Nakamura, Masanobu Ohishi, Tomoya Matsunobu, Yasuharu Nakashima, Akio Sakamoto, Akira Maekawa, Yoshinao Oda, Yukihide Iwamoto
We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion...
May 4, 2016: Modern Rheumatology
Chien-Kuo Han, Yun-Chen Tien, Dennis Jine-Yuan Hsieh, Tsung-Jung Ho, Chao-Hung Lai, Yu-Lan Yeh, Cecilia Hsuan Day, Chia-Yao Shen, Hsi-Hsien Hsu, Jing-Ying Lin, Chih-Yang Huang
Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. LPS was previously found to dramatically upregulate expression of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 in primary cardiac fibroblasts. MMPs are capable of denaturing and degrading fibrillar collagens and other components of the extracellular matrix (ECM). Studies have shown that dysregulation of expression of MMPs is associated with development of myocardial extracellular matrix remodeling and cardiac fibrosis, which contribute to progression of heart failure...
April 20, 2016: Environmental Toxicology
N A Mukhin, Yu S Milovanov, L V Kozlovskaya, I A Dobrosmyslov, L Yu Milovanova
AIM: To study whether the excessive production of serum fibroblast growth factor 23 (FGF-23) may be reduced with phosphate-binding agents to treat hyperphosphatemia in patients with Stage VD chronic kidney disease (CKD). MATERIALS AND METHODS: The investigation enrolled 25 patients with Stage VD CKD on regular hemodialysis (HD) (12 patients with chronic glomerulonephritis, 8 with tubulointerstitial nephritis, and 5 with hypertensive nephrosclerosis); among them there were 15 men and 10 women at the age of 21 to 65 years; their mean age at inclusion in the study was 43±4...
2016: Terapevticheskiĭ Arkhiv
Yusuke Minematsu, Masafumi Yamato, Yuta Ikemiya, Takahito Ito
BACKGROUND: The most frequent cause of acute kidney injury (AKI) needing renal replacement therapy is sepsis, with the prognosis of patients with septic AKI worse than for other causes of this disease. Recent studies have shown that fibroblast growth factor-23 (FGF-23) levels, one of the phosphaturic and prognostic factors in chronic kidney disease, are also elevated in patients with AKI and correlate with an increased risk of death or a need for dialysis. In addition, FGF-23 was found to inhibit the extra-renal synthesis of 1,25-dihydroxyvitamin D by human monocytes...
2016: Clinical Laboratory
Masafumi Yamato, Kaori Takaori, Yoko Tomiyama, Ryuta Fujimura, Chisako Yokobatake, Akira Wada, Takahito Ito
BACKGROUND: Plasma PTH levels are normally high during the night and early morning and lowest at approximately 10 am (the PTH circadian rhythm). Our objective was to examine the relationship between the PTH circadian rhythm and calcium-phosphorus metabolism in non-dialyzed, chronic kidney disease (CKD) patients. METHODS: The characteristics of twenty-eight subjects comprised: male, 23; diabetic patients, 16; mean age, 71.1 +/- 10.5 years; mean eGFR, 18.3 +/- 8.1 mL/min/1...
2016: Clinical Laboratory
Shennin N Yuen, Holly Kramer, Amy Luke, Pascal Bovet, Jacob Plange-Rhule, Terrence Forrester, Vicki Lambert, Myles Wolf, Pauline Camacho, Regina Harders, Lara Dugas, Richard Cooper, Ramon Durazo-Arvizu
CONTEXT: Compensatory increases in fibroblast growth factor 23 (FGF23) with increasing phosphate intake may adversely impact health. However, population and clinical studies examining the link between phosphate intake and FGF23 levels have focused mainly on populations living in highly industrialized societies in which phosphate exposure may be homogenous. OBJECTIVE: The objective of the study was to contrast dietary phosphate intake, urinary measures of phosphate excretion, and FGF23 levels across populations that differ by the level of industrialization...
May 2016: Journal of Clinical Endocrinology and Metabolism
Javad Baharara, Elaheh Amini, Marzieh Mousavi
BACKGROUND: Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. METHODS: The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR...
April 2015: Reports of Biochemistry & Molecular Biology
Lizhen Chen, Man Jiang, Yongning Xin, Jian Wang, Yang Liu, Xiangjun Jiang, Shiying Xuan
OBJECTIVE: To investigate the role and mechanism of action of fibroblast growth factor-21 (FGF-21) in reducing triglyceride (TG) in the in vitro and in vivo models of nonalcoholic fatty liver disease (NAFLD). METHODS: (1) A mixture of free fatty acids was used to establish a model of steatosis in L02 cells, and the cells were treated with various concentrations of FGF-21 or fenofibrate. Twenty-four hours later, oil red O staining was performed to observe the degree of steatosis, and intracellular TG content was determined...
February 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Virginia Rider, Alex Talbott, Anuradha Bhusri, Zach Krumsick, Sierra Foster, Joshua Wormington, Bruce F Kimler
Preparation of mammalian uterus for embryo implantation requires a precise sequence of cell proliferation. In rodent uterus, estradiol stimulates proliferation of epithelial cells. Progesterone operates as a molecular switch and redirects proliferation to the stroma by down-regulating glycogen synthase kinase-3β (GSK-3β) and stimulating β-catenin accumulation in the periluminal stromal cells. In this study, the WNT signal involved in the progesterone-dependent proliferative switch was investigated. Transcripts of four candidate Wnt genes were measured in the uteri from ovariectomized (OVX) rats, progesterone-pretreated (3 days of progesterone, 2mg/daily) rats, and progesterone-pretreated rats given a single dose (0...
May 2016: Journal of Endocrinology
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