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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
#1
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/29765501/peroxisomal-acyl-coa-oxidase-type-1-anti-inflammatory-and-anti-aging-properties-with-a-special-emphasis-on-studies-with-lps-and-argan-oil-as-a-model-transposable-to-aging
#2
REVIEW
Joseph Vamecq, Pierre Andreoletti, Riad El Kebbaj, Fatima-Ezzahra Saih, Norbert Latruffe, M' Hammed Saïd El Kebbaj, Gérard Lizard, Boubker Nasser, Mustapha Cherkaoui-Malki
To clarify appropriateness of current claims for health and wellness virtues of argan oil, studies were conducted in inflammatory states. LPS induces inflammation with reduction of PGC1- α signaling and energy metabolism. Argan oil protected the liver against LPS toxicity and interestingly enough preservation of peroxisomal acyl-CoA oxidase type 1 (ACOX1) activity against depression by LPS. This model of LPS-driven toxicity circumvented by argan oil along with a key anti-inflammatory role attributed to ACOX1 has been here transposed to model aging...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29734515/decreased-placental-and-muscular-expression-of-the-fibroblast-growth-factor-19-in-gestational-diabetes-mellitus
#3
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/29733511/lenvatinib-inhibits-angiogenesis-and-tumor-fibroblast-growth-factor-signaling-pathways-in-human-hepatocellular-carcinoma-models
#4
Masahiro Matsuki, Taisuke Hoshi, Yuji Yamamoto, Megumi Ikemori-Kawada, Yukinori Minoshima, Yasuhiro Funahashi, Junji Matsui
Unresectable hepatocellular carcinoma (uHCC) is one of the most lethal and prevalent cancers worldwide, and current systemic therapeutic options for uHCC are limited. Lenvatinib, a multiple receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), recently demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority to sorafenib in a phase 3 study of uHCC. Here, we investigated mechanisms underlying the antitumor activity of lenvatinib in preclinical HCC models...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29717197/effects-of-ngm282-an-fgf19-variant-on-colonic-transit-and-bowel-function-in-functional-constipation-a-randomized-phase-2-trial
#5
Ibironke Oduyebo, Michael Camilleri, Alfred D Nelson, Disha Khemani, Sara Linker Nord, Irene Busciglio, Duane Burton, Deborah Rhoten, Michael Ryks, Paula Carlson, Leslie Donato, Alan Lueke, Kathline Kim, Stephen J Rossi, Alan R Zinsmeister
OBJECTIVE: NGM282 is an analog of fibroblast growth factor 19 (FGF19), a potent inhibitor of bile acid (BA) synthesis in animals and humans. In phase 2 trials in type 2 diabetes and primary biliary cholangitis, NGM282 was associated with dose-related abdominal cramping and diarrhea. We aimed to examine effects of NGM282 on colonic transit, stool frequency and consistency, hepatic BA synthesis (fasting serum C4), fecal fat, and BA in functional constipation (FC). METHODS: Two-dose NGM282 (1 and 6 mg, subcutaneously daily), parallel-group, randomized, placebo-controlled, 14-day study in patients with FC (Rome III criteria) and baseline colonic transit 24 h geometric center (GC) <3...
May 2, 2018: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/29704228/a-prospective-randomized-controlled-trial-of-the-metabolic-effects-of-sleeve-gastrectomy-with-transit-bipartition
#6
Fernanda R Azevedo, Sergio Santoro, Maria L Correa-Giannella, Marcos T Toyoshima, Daniel Giannella-Neto, Daniela Calderaro, Danielle M Gualandro, Pai C Yu, Bruno Caramelli
PURPOSE: To compare the effects of the sleeve gastrectomy with transit bipartition (SG + TB) procedure with standard medical therapy (SMT) in mildly obese patients with type II diabetes (T2D). METHODS: This is a prospective, randomized, controlled trial. Twenty male adults, ≤ 65 years old, with T2D, body mass index (BMI) > 28 kg/m2 and < 35 kg/m2 , and HbA1c level > 8% were randomized to SG + TB or to SMT. Outcomes were the remission in the metabolic and cardiovascular risk variables up to 24 months...
April 27, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29701901/no-gut-no-gain-enteral-bile-acid-treatment-preserves-gut-growth-but-not-parenteral-nutrition-associated-liver-injury-in-a-novel-extensive-short-bowel-animal-model
#7
Gustavo Villalona, Amber Price, Keith Blomenkamp, Chandrashekhara Manithody, Saurabh Saxena, Thomas Ratchford, Matthew Westrich, Vindhya Kakarla, Shruthika Pochampally, William Phillips, Nicole Heafner, Niraja Korremla, Jose Greenspon, Miguel A Guzman, Ajay Kumar Jain
BACKGROUND: Parenteral nutrition (PN) provides nutrition intravenously; however, this life-saving therapy is associated with significant liver disease. Recent evidence indicates improvement in PN-associated injury in animals with intact gut treated with enteral bile acid (BA), chenodeoxycholic acid (CDCA), and a gut farnesoid X receptor (FXR) agonist, which drives the gut-liver cross talk (GLCT). We hypothesized that similar improvement could be translated in animals with short bowel syndrome (SBS)...
April 27, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29699061/expression-of-fibroblast-growth-factor-21-and-%C3%AE-klotho-regulates-hepatic-fibrosis-through-the-nuclear-factor-%C3%AE%C2%BAb-and-c-jun-n-terminal-kinase-pathways
#8
Kyong Joo Lee, Yoon Ok Jang, Seung-Kuy Cha, Moon Young Kim, Kyu-Sang Park, Young Woo Eom, Soon Koo Baik
Background/Aims: Fibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver. Methods: Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells...
April 27, 2018: Gut and Liver
https://www.readbyqxmd.com/read/29622814/nash-successful-phase-ii-trial-of-fgf19-analogue
#9
Iain Dickson
No abstract text is available yet for this article.
April 6, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29615519/fgf21-acts-as-a-negative-regulator-of-bile-acid-synthesis
#10
Michelle M Chen, Clarence Hale, Shanaka Stanislaus, Jing Xu, Murielle M Véniant
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid homeostasis in vivo ; its most closely related subfamily member, FGF19, is known to be a critical negative regulator of bile acid synthesis. To delineate whether FGF21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native FGF21 and long-acting FGF21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary hepatocytes and in rodent and monkey models...
May 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29582208/update-on-bile-acid-malabsorption-finally-ready-for-prime-time
#11
REVIEW
Priya Vijayvargiya, Michael Camilleri
PURPOSE OF REVIEW: To provide an update on the prevalence, pathophysiology, disease associations, and treatment options for bile acid malabsorption (BAM). RECENT FINDINGS: •Molecular mechanisms-BAs prevent water reabsorption and increase water secretion by intracellular mediators, increasing aquaporin channels and intracellular permeability. •Inflammatory bowel disease-new molecular mechanisms of BAM are identified in patients without ileal disease, including changes in expression of ileal BA transporter and nuclear receptors involved in BA homeostasis...
March 26, 2018: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29557750/interrupting-the-fgf19-fgfr4-axis-to-therapeutically-disrupt-cancer-progression
#12
Liwei Lang, Austin Y Shull, Yong Teng
Coordination between amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho have been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers...
March 18, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29552326/research-progress-on-the-forkhead-box-c1
#13
REVIEW
Jinhua Wang, Wan Li, Xiangjin Zheng, Xiaocong Pang, Guanhua Du
FOXC1 is a vital member of FOX families which play important roles in biological processes including proliferation, differentiation, apoptosis, migration, invasion, metabolism, and longevity. Here we are focusing on roles of FOXC1 and their mechanisms in cancers. FOXC1 promoted progress of many cancers, such as breast cancer (especially basal-like breast cancer), hepatocellular carcinoma, gastric cancer and so on. FOXC1 was also found to be associated with drug resistance of cancers. FOXC1 promoted metastasis of cancers by increasing expression of MMP7, NEDD9 and Snail...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29546316/cd36-modulates-fasting-and-preabsorptive-hormone-and-bile-acid-levels
#14
Cyndya A Shibao, Jorge E Celedonio, Robyn Tamboli, Reem Sidani, Latisha Love-Gregory, Terri Pietka, Yanhua Xiong, Yan Wei, Naji N Abumrad, Nada A Abumrad, Charles Robb Flynn
Context: Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism, but whether it has similar actions in humans is unknown. We examined the impact of a coding single-nucleotide polymorphism in CD36 on postprandial hormone and bile acid (BA) responses. Objective: To examine whether the minor allele (G) of coding CD36 variant rs3211938 (G/T), which reduces CD36 level by ∼50%, influences hormonal responses to a high-fat meal (HFM)...
May 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29519502/ngm282-for-treatment-of-non-alcoholic-steatohepatitis-a-multicentre-randomised-double-blind-placebo-controlled-phase-2-trial
#15
Stephen A Harrison, Mary E Rinella, Manal F Abdelmalek, James F Trotter, Angelo H Paredes, Hays L Arnold, Marcelo Kugelmas, Mustafa R Bashir, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Rohit Loomba
BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA...
March 24, 2018: Lancet
https://www.readbyqxmd.com/read/29499231/elucidation-of-possible-molecular-mechanisms-underlying-the-estrogen-induced-disruption-of-cartilage-development-in-zebrafish-larvae
#16
Hanliang He, Chunqing Wang, Qifeng Tang, Fan Yang, Youjia Xu
Estrogen can affect the cartilage development of zebrafish; however, the mechanism underlying its effects is not completely understood. Four-day-old zebrafish larvae were treated with 0.8 μM estrogen, the 5 days post fertilization (dpf) zebrafish larvae did not demonstrate obvious abnormalities during development; however, the 6 dpf and 7 dpf larvae exhibited abnormal craniofacial bone development along with craniofacial bone degradation. RNA deep sequencing was performed to elucidate the mechanism involved...
June 1, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29468415/the-ileal-fgf15-19-to-hepatic-fgfr4-axis-regulates-liver-regeneration-after-partial-hepatectomy-in-mice
#17
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/29460642/novel-targeted-therapy-strategies-for-biliary-tract-cancers-and-hepatocellular-carcinoma
#18
Thomas T DeLeon, Daniel H Ahn, James M Bogenberger, Panos Z Anastasiadis, Mansi Arora, Ramesh K Ramanathan, Bashar A Aqel, George Vasmatzis, Mark J Truty, Rahmi Oklu, Tanios S Bekaii-Saab, Mitesh J Borad
Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement...
March 2018: Future Oncology
https://www.readbyqxmd.com/read/29446652/developmental-regulation-of-the-intestinal-fgf19-system-in-domestic-pigs
#19
Aleix Gavaldà-Navarro, Jose J Pastor, Alessandro Mereu, Francesc Villarroya, Ignacio R Ipharraguerre
Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in the regulation of bile acid homeostasis and energy metabolism in rodents and humans. In pigs, however, the FGF19 system remains largely unexplored. This study was designed to investigate the developmental regulation of the FGF19 system in domestic pigs. Samples of intestinal sections, liver, and plasma were collected from 24 pigs (n = 6) at four developmental stages (birth, pre-weaning, post-weaning, and adulthood). In the intestine, expression of the farnesoid X receptor (FXR) and FGF19 showed a congruent time- and region-dependent regulation, beginning soon after birth to achieve maximal expression in ileum during adulthood...
February 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29438906/alteration-in-the-serum-concentrations-of-fgf19-fgfr4-and-%C3%AE-klotho-in-patients-with-thyroid-cancer
#20
Ewelina Motylewska, Tomasz Stępień, Magdalena Borkowska, Krzysztof Kuzdak, Agnieszka Siejka, Jan Komorowski, Henryk Stępień, Hanna Ławnicka
INTRODUCTION: βKlotho (βKL) is known to act as co-receptor for fibroblast growth factor receptor 4 (FGFR4) which is the main cognate receptor for fibroblast growth factor 19 (FGF19). Dysregulation of this FGF19/FGFR4/βKL signaling axis has been implicated in the pathogenesis of several cancers. However, its role in the pathogenesis of thyroid cancer has not been determined. MATERIALS AND METHODS: The aim of this study was to assess FGF19, FGFR4 and βKL concentrations in a group of 36 patients with papillary thyroid cancer (PTC), 11 patients with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and a group of 19 subjects with multinodular nontoxic goiter (MNG)...
May 2018: Cytokine
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