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https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#1
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28522899/the-metabolic-syndrome-inflammation-and-colorectal-cancer-risk-an-evaluation-of-large-panels-of-plasma-protein-markers-using-repeated-prediagnostic-samples
#2
Sophia Harlid, Robin Myte, Bethany Van Guelpen
Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#3
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#4
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401422/acetate-free-biofiltration-to-remove-fibroblast-growth-factor-23-in-hemodialysis-patients-a-pilot-study
#5
Valeria Cernaro, Silvia Lucisano, Valeria Canale, Annamaria Bruzzese, Daniela Caccamo, Giuseppe Costantino, Michele Buemi, Domenico Santoro
AIM: Serum levels of 32 kDa-phosphaturic hormone fibroblast growth factor 23 (FGF23) rise early in renal failure in order to keep phosphatemia within the normal range; however, this compensatory mechanism itself contributes to chronic kidney disease-mineral bone disorder. High FGF23 is also associated to left ventricular hypertrophy, vascular calcifications and thus increased cardiovascular risk. The aim of this pilot pre-post study was to evaluate the effects of a single hemodiafiltration session with acetate-free biofiltration (AFB) on FGF23 serum levels...
April 11, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28378806/fibroblast-growth-factor-2-drives-and-maintains-progressive-corneal-neovascularization-following-hsv-1-infection
#6
H R Gurung, M M Carr, K Bryant, A J Chucair-Elliott, D Jj Carr
Herpes simplex virus type 1 (HSV-1) infection of the cornea induces vascular endothelial growth factor A (VEGF-A)-dependent lymphangiogenesis that continues to develop well beyond the resolution of infection. Inflammatory leukocytes infiltrate the cornea and have been implicated to be essential for corneal neovascularization, an important clinically relevant manifestation of stromal keratitis. Here we report that cornea infiltrating leukocytes including neutrophils and T cells do not have a significant role in corneal neovascularization past virus clearance...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#7
REVIEW
Zhe Huang, Aimin Xu, Bernard M Y Cheung
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28326329/diagnostic-value-of-ck-18-fgf-21-and-related-biomarker-panel-in-nonalcoholic-fatty-liver-disease-a-systematic-review-and-meta-analysis
#8
REVIEW
Lei He, Linfeng Deng, Quan Zhang, Jianli Guo, Jinan Zhou, Wenjian Song, Fahu Yuan
Liver biopsy still remains the gold standard for diagnosing nonalcoholic steatohepatitis (NASH), but with limitations. There is an urgent need to develop noninvasive tests that accurately distinguish NASH from simple steatosis. The purpose of this meta-analysis was to evaluate the diagnostic value of serum biomarkers including cytokeratin 18 (CK-18), fibroblast growth factor 21 (FGF-21), and combined biomarker panel (CBP) in the diagnosis of NAFLD, especially NASH. A total of 25 studies met the inclusion criteria...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#9
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28289333/influence-of-vaginal-lactoferrin-administration-on-amniotic-fluid-cytokines-and-its-role-against-inflammatory-complications-of-pregnancy
#10
Martina Maritati, Manola Comar, Nunzia Zanotta, Silva Seraceni, Alessandro Trentini, Fabrizio Corazza, Fortunato Vesce, Carlo Contini
BACKGROUND: An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Up to this date there is no exhaustive information neither on the foetal cytokine balance nor on the best method for its modulation. We aimed to evaluate the influence of vaginal lactoferrin administration on amniotic fluid concentration of 47 cytokines, chemokines and growth factors. METHODS: Sixty women undergoing genetic amniocentesis were enrolled in an open-label clinical trial...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28249286/impact-of-fibroblast-growth-factors-19-and-21-in-bariatric-metabolism
#11
REVIEW
Ashley Patton, Farooq H Khan, Rohit Kohli
BACKGROUND: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28225059/decreased-levels-of-fibroblast-growth-factor-21-are-correlated-with-improved-hypoglycemia-in-patients-with-insulinoma
#12
Xu Li, Haoyong Yu, Jun Yin, Lianxi Li, Jian Zhou, Ming Li, Qing Li, Haibing Chen, Fang Liu, Yuqian Bao, Junfeng Han, Weiping Jia
Fibroblast growth factor-21 (FGF-21) improves insulin sensitivity and lipid metabolism in obese or diabetic animal models and has been proposed as a potential therapeutic agent for treating T2DM, obesity, and their related complications. However, little is known about the changes of FGF21 levels in response to endogenous hyperinsulinemic hypoglycemia. To explore its relationship with parameters of glucose metabolism in patients with insulinoma, eleven subjects with pathological insulinoma and twenty-two healthy subjects were recruited for this study...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106545/the-alterations-of-serum-fgf-21-levels-metabolic-and-body-composition-in-early-breast-cancer-patients-receiving-adjuvant-endocrine-therapy
#13
Murat Akyol, Ahmet Alacacioglu, Leyla Demir, Yuksel Kucukzeybek, Yasar Yildiz, Zehra Gumus, Mete Kara, Tarik Salman, Umut Varol, Halil Taskaynatan, Utku Oflazoglu, Vedat Bayoglu, Mustafa Oktay Tarhan
BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy...
2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#14
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
March 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28069899/lps-infusion-suppresses-serum-fgf21-levels-in-healthy-adult-volunteers
#15
Esben S Lauritzen, Nikolaj Rittig, Ermina Bach, Niels Møller, Mette Bjerre
CONTEXT: During the inflammatory acute phase response, plasma glucose and serum triglycerides are increased in humans. Fibroblast growth factor (FGF) 21 has plasma glucose and lipid-reducing actions, but its role in the acute inflammatory response in human is unknown. OBJECTIVE: To investigate circulating levels of FGF21 after lipopolysaccharide (LPS) infusion. DESIGN: Two randomized, single-blinded, placebo-controlled crossover trials were used...
January 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28060761/identification-of-micrornas-associated-with-glioma-diagnosis-and-prognosis
#16
Xinyun Ye, Wenjin Wei, Zhengyu Zhang, Chunming He, Ruijin Yang, Jinshi Zhang, Zhiwu Wu, Qianliang Huang, Qiuhua Jiang
The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#17
Jun Zhang, Jamila Gupte, Yan Gong, Jennifer Weiszmann, Yuan Zhang, Ki Jeong Lee, William G Richards, Yang Li
Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28039838/fibroblast-growth-factor-21-and-its-novel-association-with-oxidative-stress
#18
REVIEW
Miguel Ángel Gómez-Sámano, Mariana Grajales-Gómez, Julia María Zuarth-Vázquez, Ma Fernanda Navarro-Flores, Mayela Martínez-Saavedra, Óscar Alfredo Juárez-León, Mariana G Morales-García, Víctor Manuel Enríquez-Estrada, Francisco J Gómez-Pérez, Daniel Cuevas-Ramos
Fibroblast growth factor 21 (FGF21) is an endocrine-member of the FGF family. It is synthesized mainly in the liver, but it is also expressed in adipose tissue, skeletal muscle, and many other organs. It has a key role in glucose and lipid metabolism, as well as in energy balance. FGF21 concentration in plasma is increased in patients with obesity, insulin resistance, and metabolic syndrome. Recent findings suggest that such increment protects tissue from an increased oxidative stress environment. Different types of physical stress, such as strenuous exercising, lactation, diabetic nephropathy, cardiovascular disease, and critical illnesses, also increase FGF21 circulating concentration...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28017785/hepatic-lipid-metabolism-and-non-alcoholic-fatty-liver-disease-in-aging
#19
Zhenwei Gong, Emir Tas, Shoshana Yakar, Radhika Muzumdar
Aging is associated with dysregulation of glucose and lipid metabolism. Various factors that contribute to the dysregulation include both modifiable (e.g. obesity, insulin resistance) and non-modifiable risk factors (age-associated physiologic changes). Although there is no linear relationship between aging and prevalence of non-alcoholic fatty liver disease, current data strongly suggests that advanced age leads to more severe histological changes and poorer clinical outcomes. Hepatic lipid accumulation could lead to significant hepatic and systemic consequences including steatohepatitis, cirrhosis, impairment of systemic glucose metabolism and metabolic syndrome, thereby contributing to age-related diseases...
December 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28005535/ectopic-adipose-tissue-storage-in-the-left-and-the-right-renal-sinus-is-asymmetric-and-associated-with-serum-kidney-injury-molecule-1-and-fibroblast-growth-factor-21-levels-increase
#20
Gita Krievina, Peteris Tretjakovs, Ilze Skuja, Vija Silina, Laura Keisa, Daiga Krievina, Guntis Bahs
OBJECTIVE: A potential mechanism by which obesity could promote hypertension and kidney diseases is through accumulation of adipose tissue in the renal sinus (RS). The aim of the study was to quantify RS and abdominal adipose tissue volumes and to evaluate serum kidney injury molecule (sKIM)-1 and fibroblast growth factor (FGF)-21 association with different adipose tissue compartments. METHODS: The cross-sectional study included 280 and follow-up study-40 asymptomatic participants; aged 38...
November 2016: EBioMedicine
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