keyword
https://read.qxmd.com/read/38343040/simulation-based-evaluation-of-personalized-dosing-approaches-for-anti-fgfr-klb-bispecific-antibody-fazpilodemab
#1
Kenta Yoshida, Victor Poon, Ajit Dash, Rebecca Kunder, Leslie Chinn, Matts Kågedal
Personalized dosing approaches play important roles in clinical practices to improve benefit: risk profiles. Whereas this is also important for drug development, especially in the context of drugs with narrow therapeutic windows, such approaches have not been fully evaluated during clinical development. Fazpilodemab (BFKB8488A) is an agonistic bispecific antibody which was being developed for the treatment of nonalcoholic steatohepatitis. The objective of this study was to characterize the exposure-response relationships of fazpilodemab with the purpose of guiding dose selection for a phase II study, as well as to evaluate various personalized dosing strategies to optimize the treatment benefit...
February 11, 2024: CPT: Pharmacometrics & Systems Pharmacology
https://read.qxmd.com/read/38277453/genetic-architecture-of-alcohol-consumption-identified-by-a-genotype-stratified-gwas-and-impact-on-esophageal-cancer-risk-in-japanese-people
#2
JOURNAL ARTICLE
Yuriko N Koyanagi, Masahiro Nakatochi, Shinichi Namba, Isao Oze, Hadrien Charvat, Akira Narita, Takahisa Kawaguchi, Hiroaki Ikezaki, Asahi Hishida, Megumi Hara, Toshiro Takezaki, Teruhide Koyama, Yohko Nakamura, Sadao Suzuki, Sakurako Katsuura-Kamano, Kiyonori Kuriki, Yasuyuki Nakamura, Kenji Takeuchi, Atsushi Hozawa, Kengo Kinoshita, Yoichi Sutoh, Kozo Tanno, Atsushi Shimizu, Hidemi Ito, Yumiko Kasugai, Yukino Kawakatsu, Yukari Taniyama, Masahiro Tajika, Yasuhiro Shimizu, Etsuji Suzuki, Yasuyuki Hosono, Issei Imoto, Yasuharu Tabara, Meiko Takahashi, Kazuya Setoh, Koichi Matsuda, Shiori Nakano, Atsushi Goto, Ryoko Katagiri, Taiki Yamaji, Norie Sawada, Shoichiro Tsugane, Kenji Wakai, Masayuki Yamamoto, Makoto Sasaki, Fumihiko Matsuda, Yukinori Okada, Motoki Iwasaki, Paul Brennan, Keitaro Matsuo
An East Asian-specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci ( GCKR , KLB , and ADH1B ) in wild-type homozygotes and six ( GCKR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , and GOT2 ) in heterozygotes, with five showing genome-wide significant interaction with rs671...
January 26, 2024: Science Advances
https://read.qxmd.com/read/38212977/targeting-the-fgf19-fgfr4-pathway-for-cholestatic-metabolic-and-cancerous-diseases
#3
REVIEW
Xiaokun Li, Weiqin Lu, Alexei Kharitonenkov, Yongde Luo
Human fibroblast growth factor 19 (FGF19, or FGF15 in rodents) plays a central role in controlling bile acid (BA) synthesis through a negative feedback mechanism. This process involves a postprandial crosstalk between the BA-activated ileal farnesoid X receptor and the hepatic Klotho beta (KLB) coreceptor complexed with fibrobalst growth factor receptor 4 (FGFR4) kinase. Additionally, FGF19 regulates glucose, lipid, and energy metabolism by coordinating responses from functional KLB and FGFR1-3 receptor complexes on the periphery...
March 2024: Journal of Internal Medicine
https://read.qxmd.com/read/38158702/exploring-biomarkers-in-trigeminal-neuralgia-patients-operated-with-microvascular-decompression-a-comparison-with-multiple-sclerosis-patients-and-non-neurological-controls
#4
JOURNAL ARTICLE
Muataz S Lafta, Aleksandr V Sokolov, Anne-Marie Landtblom, Hans Ericson, Helgi B Schiöth, Sami Abu Hamdeh
BACKGROUND: Trigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co-occurs with multiple sclerosis (MS). METHODS: We analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro-Exploratory panel provided by SciLifeLab, Uppsala, Sweden...
December 29, 2023: European Journal of Pain: EJP
https://read.qxmd.com/read/38141848/lysine-trna-fragments-and-mir-194-5p-co-regulate-hepatic-steatosis-via-%C3%AE-klotho-and-perilipin-2
#5
JOURNAL ARTICLE
Yonat Tzur, Katarzyna Winek, Nimrod Madrer, Serafima Dubnov, Estelle R Bennett, David S Greenberg, Geula Hanin, Asaad Gammal, Joseph Tam, Isaiah T Arkin, Iddo Paldor, Hermona Soreq
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5'tRF transfer RNA fragments and microRNA miR-194-5p. METHODS: Combined use of diet induced obese mice with human-derived oleic acid-exposed Hep G2 cells revealed new NAFLD roles of LysTTT-5'tRF and miR-194-5p. RESULTS: Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5'tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis...
January 2024: Molecular Metabolism
https://read.qxmd.com/read/38117265/vertical-sleeve-gastrectomy-improves-glucose-insulin-homeostasis-by-enhancing-beta-cell-function-and-survival-via-fgf15-19
#6
JOURNAL ARTICLE
Gabriela M Soares, Sandra L Balbo, Gabriela A Bronczek, Jean F Vettorazzi, Carine Marmentini, Lucas Zangerolamo, Licio A Velloso, Everardo M Carneiro
Vertical sleeve gastrectomy (VSG) restores glucose homeostasis in obese mice and humans. In addition, the increased fibroblast growth factor (FGF)15/19 circulating level post-surgery has been implicated in this effect. However, the impact of FGF15/19 on pancreatic islets remains unclear. Using a diet-induced obese mice model, we demonstrate that VSG attenuates insulin hypersecretion in isolated pancreatic islets, likely due to morphological alterations in the endocrine pancreas such as reduction in islet, beta cell, and alpha cell mass...
December 20, 2023: American Journal of Physiology. Endocrinology and Metabolism
https://read.qxmd.com/read/37900130/identification-of-optimal-feature-genes-in-patients-with-thyroid-associated-ophthalmopathy-and-their-relationship-with-immune-infiltration-a-bioinformatics-analysis
#7
JOURNAL ARTICLE
Chao Xiong, Yaohua Wang, Yue Li, Jinhai Yu, Sha Wu, Lili Wu, Boyuan Zhang, Yunxiu Chen, Puying Gan, Hongfei Liao
BACKGROUND: Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that has a significant impact on individuals and society. The etiology of TAO is complicated and poorly understood. Thus, the goal of this study was to use bioinformatics to look into the pathogenesis of TAO and to identify the optimum feature genes (OFGs) and immune infiltration patterns of TAO. METHODS: Firstly, the GSE58331 microarray data set was utilized to find 366 differentially expressed genes (DEGs)...
2023: Frontiers in Endocrinology
https://read.qxmd.com/read/37889055/pegozafermin-is-a-potential-master-therapeutic-regulator-in-metabolic-disorders-a-review
#8
JOURNAL ARTICLE
Nadian N Bailey, Stephen J Peterson, Manish A Parikh, Kaedrea A Jackson, William H Frishman
Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues...
October 27, 2023: Cardiology in Review
https://read.qxmd.com/read/37789318/engineered-fgf19-%C3%AE-klb-protects-against-intrahepatic-cholestatic-liver-injury-in-anit-induced-and-mdr2-mice-model
#9
JOURNAL ARTICLE
Lu Shi, Tiantian Zhao, Lei Huang, Xiaomin Pan, Tianzhen Wu, Xin Feng, Taoli Chen, Jiamin Wu, Jianlou Niu
BACKGROUND: The major safety concern of the clinical application of wild type FGF19 (FGF19WT ) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB , which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis. RESULTS: We found that, similar to that of FGF19WT , the chronic administration of FGF19ΔKLB protects mice from cholestatic liver injury in these two models...
October 3, 2023: BMC Biotechnology
https://read.qxmd.com/read/37582861/klotho-beta-attenuates-rab8a-mediated-exosome-regulation-and-promotes-prostate-cancer-progression
#10
JOURNAL ARTICLE
Tingyu Wu, Yanshuang Zhang, Qing Han, Xin Lu, Yirui Cheng, Jiachen Chen, Jianjun Sha, Weiliang Xia
Tumor-secreted exosomes have a wide range of effects on the growth, metastasis, and drug resistance of cancer cells. However, whether and how the molecular mechanisms that regulate the secretion of exosomes could affect tumor progression remains poorly understood. Klotho beta (KLB) has been reported dysregulated in prostate cancer, but its function remains unknown. Herein, we first determined that KLB was upregulated in prostate cancer and its expression level was positively correlated with prostate cancer malignant phenotype both in vitro and in vivo...
September 2023: Oncogene
https://read.qxmd.com/read/37454120/fgf19-induces-the-cell-cycle-arrest-at-g2-phase-in-chondrocytes
#11
JOURNAL ARTICLE
Hao Chen, Jiazhou Li, Caixia Pi, Daimo Guo, Demao Zhang, Xuedong Zhou, Jing Xie
Fibroblast growth factor 19 (FGF19) has appeared as a new possible avenue in the treatment of skeletal metabolic disorders. However, the role of FGF19 on cell cycle progression in skeletal system is poorly understood. Here we demonstrated that FGF19 had the ability to reduce the proliferation of chondrocytes and cause cell cycle G2 phase arrest through its interaction with β-Klotho (KLB), an important accessory protein that helps FGF19 link to its receptor. FGF19-mediated cell cycle arrest by regulating the expressions of cdk1/cylinb1, chk1 and gadd45a...
July 15, 2023: Cell Death Discovery
https://read.qxmd.com/read/37350415/aberrant-acetylated-modification-of-fgf21%C3%A2-klb-signaling-contributes-to-hepatocellular-carcinoma-metastasis-through-the-%C3%AE-%C3%A2-catenin-pathway
#12
JOURNAL ARTICLE
Jinkun Xia, Zhengyi Zhu, Gaolin Wen, Yuyan Chen, Ran An, Senzhe Xia, Wenxian Guan, Haozhen Ren
β‑Klotho (KLB) is a vital element of the fibroblast growth factor (FGF) receptor complex and acts as a co‑receptor to facilitate the binding of FGF19 and FGF21 to the FGFRs on the target cells. The present study aimed to determine the contribution of FGF21‑KLB signaling to hepatocellular carcinoma (HCC) metastasis. KLB expression was measured in HCC tissues and cell lines using western blot and reverse transcription‑quantitative PCR. Furthermore, the proliferation, apoptosis and metastasis capacity of KLB‑knockdown Huh7 cells (human HCC cell line) were assessed by Cell Counting Kit‑8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, wound‑healing assay and Transwell assay...
August 2023: International Journal of Oncology
https://read.qxmd.com/read/37282749/epigenetic-regulation-of-hepatic-lipid-metabolism-by-dna-methylation
#13
JOURNAL ARTICLE
Shirong Wang, Lin Zha, Xin Cui, Yu-Te Yeh, Ruochuan Liu, Jia Jing, Huidong Shi, Weiping Chen, John Hanover, Jun Yin, Liqing Yu, Bingzhong Xue, Hang Shi
While extensive investigations have been devoted to the study of genetic pathways related to fatty liver diseases, much less is known about epigenetic mechanisms underlying these disorders. DNA methylation is an epigenetic link between environmental factors (e.g., diets) and complex diseases (e.g., non-alcoholic fatty liver disease). Here, it is aimed to study the role of DNA methylation in the regulation of hepatic lipid metabolism. A dynamic change in the DNA methylome in the liver of high-fat diet (HFD)-fed mice is discovered, including a marked increase in DNA methylation at the promoter of Beta-klotho (Klb), a co-receptor for the biological functions of fibroblast growth factor (FGF)15/19 and FGF21...
June 6, 2023: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/37260446/biological-and-pharmacological-functions-of-the-fgf19-and-fgf21-coreceptor-beta-klotho
#14
REVIEW
Alexandra S Aaldijk, Cristy R C Verzijl, Johan W Jonker, Dicky Struik
Beta klotho (KLB) is a fundamental component in fibroblast growth factor receptor (FGFR) signaling as it serves as an obligatory coreceptor for the endocrine hormones fibroblast growth factor 19 (FGF19) and fibroblast growth factor 21 (FGF21). Through the development of FGF19- and FGF21 mimetics, KLB has emerged as a promising drug target for treating various metabolic diseases, such as type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. While rodent studies have significantly increased our understanding of KLB function, current clinical trials that test the safety and efficacy of KLB-targeting drugs raise many new scientific questions about human KLB biology...
2023: Frontiers in Endocrinology
https://read.qxmd.com/read/37030441/fibroblast-growth-factor-21-is-required-for-weight-loss-induced-by-the-glucagon-like-peptide-1-receptor-agonist-liraglutide-in-male-mice-fed-high-carbohydrate-diets
#15
JOURNAL ARTICLE
Thao D V Le, Payam Fathi, Amanda B Watters, Blair J Ellis, Gai-Linn K Besing, Nadejda Bozadjieva-Kramer, Misty B Perez, Andrew I Sullivan, Jesse P Rose, Laurie L Baggio, Jacqueline Koehler, Jennifer L Brown, Michelle B Bales, Kaitlyn G Nwaba, Jonathan E Campbell, Daniel J Drucker, Matthew J Potthoff, Randy J Seeley, Julio E Ayala
OBJECTIVE: Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RA) and fibroblast growth factor-21 (FGF21) confer similar metabolic benefits. GLP-1RA induce FGF21, leading us to investigate mechanisms engaged by the GLP-1RA liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21. METHODS: Circulating FGF21 levels were measured in fasted male C57BL/6J, neuronal GLP-1R knockout, β-cell GLP-1R knockout, and liver peroxisome proliferator-activated receptor alpha knockout mice treated acutely with liraglutide...
April 7, 2023: Molecular Metabolism
https://read.qxmd.com/read/37019912/klb-and-nox4-expression-levels-as-potential-blood-based-transcriptional-biomarkers-of-physical-activity-in-children
#16
JOURNAL ARTICLE
Sebastià Galmés, Azahara I Rupérez, Juana Sánchez, Luis A Moreno, Ronja Foraita, Antje Hebestreit, Dénes Molnár, Andreu Palou, Catalina Picó
Insufficient physical activity (PA) in children is considered one of the major contributors to obesity and cardiometabolic complications later in life. Although regular exercise may contribute to disease prevention and health promotion, reliable early biomarkers are required to objectively discern people performing low PA from those who exercise enough. Here, we aimed to identify potential transcript-based biomarkers through the analysis of a whole-genome microarray in peripheral blood cells (PBC) from physically less active (n = 10) comparing with more active (n = 10) children...
April 5, 2023: Scientific Reports
https://read.qxmd.com/read/36915160/fgf19-increases-mitochondrial-biogenesis-and-fusion-in-chondrocytes-via-the-ampk%C3%AE-p38-mapk-pathway
#17
JOURNAL ARTICLE
Shiyi Kan, Caixia Pi, Li Zhang, Daimo Guo, Zhixing Niu, Yang Liu, Mengmeng Duan, Xiahua Pu, Mingru Bai, Chenchen Zhou, Demao Zhang, Jing Xie
Fibroblast growth factor 19 (FGF19) is recognized to play an essential role in cartilage development and physiology, and has emerged as a potential therapeutic target for skeletal metabolic diseases. However, FGF19-mediated cellular behavior in chondrocytes remains a big challenge. In the current study, we aimed to investigate the role of FGF19 on chondrocytes by characterizing mitochondrial biogenesis and fission-fusion dynamic equilibrium and exploring the underlying mechanism. We first found that FGF19 enhanced mitochondrial biogenesis in chondrocytes with the help of β Klotho (KLB), a vital accessory protein for assisting the binding of FGF19 to its receptor, and the enhanced biogenesis accompanied with a fusion of mitochondria, reflecting in the elongation of individual mitochondria and the up-regulation of mitochondrial fusion proteins...
March 13, 2023: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/36905134/short-term-semaglutide-treatment-improves-fgf21-responsiveness-in-primary-hepatocytes-isolated-from-high-fat-diet-challenged-mice
#18
JOURNAL ARTICLE
Jia Nuo Feng, Weijuan Shao, Tianru Jin
Metabolic functions of GLP-1 and its analogues have been extensively investigated. In addition to acting as an incretin and reducing body weight, we and others have suggested the existence of GLP-1/fibroblast growth factor 21 (FGF21) axis in which liver mediates certain functions of GLP-1 receptor agonists. In a more recent study, we found with surprise that four-week treatment with liraglutide but not semaglutide stimulated hepatic FGF21 expression in HFD-challenged mice. We wondered whether semaglutide can also improve FGF21 sensitivity or responsiveness and hence triggers the feedback loop in attenuating its stimulation on hepatic FGF21 expression after a long-term treatment...
March 2023: Physiological Reports
https://read.qxmd.com/read/36764073/fluoride-regulates-the-differentiation-and-atrophy-through-fgf21-erk-signaling-pathway-in-c2c12-cells
#19
JOURNAL ARTICLE
Lan Ma, Chengmei Zhang, Yu Gui, Tingling Zou, Shuhua Xi, Xiaoying Guo
Excess intake of fluoride leads to a serious health issue called fluorosis. Fluorosis patients exhibit the symptom of muscle damage, but the specific mechanism remains unclear. Fibroblast growth factor 21 (FGF21) is a novel myokine that is involved in the regulation of myogenic differentiation, but whether fluoride induces skeletal muscle damage via FGF21 signaling has not been reported yet. In the current study, C2C12 cells were used to investigate the impact of fluoride on myogenic development and the involved regulatory role of FGF21/ERK signaling pathway...
February 8, 2023: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/36742836/-an-observational-study-on-association-of-clinical-diagnosis-of-diphtheria-with-smear-and-culture-test-a-tertiary-care-hospital-jaipur
#20
JOURNAL ARTICLE
Saket Kumar Jammar, Tanmaya Kataria, Sunita Agarwal, Shraddha Sharma, Ramlakhan Meena, Shashank Nath Singh, Rekha Harshvardhan, Ajay Gupta
Diphtheria is an acute infectious upper respiratory tract disease caused by toxigenic strains of Corynebacterium diphtheria and can lead to significant morbidity and mortality in all the age groups. Most of the time diagnosis of diphtheria is clinical. There may be a dirty white patch covering one or both tonsils on examination for which throat swabs are collected for Kleb's-Loeffler's Bacillus (KLB) by direct microscopy and for culture and sensitivity of the organism. To find out the association between clinical diagnosis of diphtheria with smear and culture positivity...
December 2022: Indian Journal of Otolaryngology and Head and Neck Surgery
keyword
keyword
88481
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.