Article
Biochemistry & Molecular Biology
Laura Vila, Nuria Cabedo, Carlos Villarroel-Vicente, Ainhoa Garcia, Alvaro Bernabeu, Nathalie Hennuyer, Bart Staels, Xavier Franck, Bruno Figadere, Maria-Jesus Sanz, Diego Cortes
Summary: The study synthesized three new series of prenylated benzopyrans containing different numbers of isoprenoid units and explored their hPPAR transactivation activity and structure activity relationships. The results demonstrated that 2-prenylated benzopyrans with seven-carbon and nine-carbon side chains are good lead compounds for preventing cardiovascular diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Juliette Lambert, Joseph Saliba, Carolina Calderon, Karine Sii-Felice, Mohammad Salma, Valerie Edmond, Jean-Claude Alvarez, Marc Delord, Caroline Marty, Isabelle Plo, Jean-Jacques Kiladjian, Eric Soler, William Vainchenker, Jean-Luc Villeval, Philippe Rousselot, Stephane Prost
Summary: Myelofibrosis is a myeloproliferative neoplasm associated with poor outcomes, and current treatments have limited effectiveness. Research has shown that PPAR gamma agonists have the potential to target and treat myelofibrosis by reducing myeloproliferation, modulating inflammation, and protecting bone marrow stroma.Activation of PPAR gamma presents a promising therapeutic target for myelofibrosis, with the possibility of using PPAR gamma agonists in clinical practice.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Gastroenterology & Hepatology
Sarra Smati, Arnaud Polizzi, Anne Fougerat, Sandrine Ellero-Simatos, Yuna Blum, Yannick Lippi, Marion Regnier, Alexia Laroyenne, Marine Huillet, Muhammad Arif, Cheng Zhang, Frederic Lasserre, Alain Marrot, Talal Al Saati, JingHong Wan, Caroline Sommer, Claire Naylies, Aurelie Batut, Celine Lukowicz, Tiffany Fougeray, Blandine Tramunt, Patricia Dubot, Lorraine Smith, Justine Bertrand-Michel, Nathalie Hennuyer, Jean-Philippe Pradere, Bart Staels, Remy Burcelin, Francoise Lenfant, Jean-Francois Arnal, Thierry Levade, Laurence Gamet-Payrastre, Sandrine Lagarrigue, Nicolas Loiseau, Sophie Lotersztajn, Catherine Postic, Walter Wahli, Christophe Bureau, Maeva Guillaume, Adil Mardinoglu, Alexandra Montagner, Pierre Gourdy, Herve Guillou
Summary: The study found that different diets induced more severe NAFLD in male mice, characterized by lipid accumulation and inflammation/fibrosis. Sex-biased hepatic gene signatures showed different responses to various dietary challenges, with Peroxisome proliferator-activated receptor alpha (PPAR alpha) playing a key role in gender-specific and NAFLD pathophysiology.
Article
Chemistry, Medicinal
Zongtao Zhou, Qiang Ren, Shixuan Jiao, Zongyu Cai, Xinqian Geng, Liming Deng, Bin Wang, Lijun Hu, Luyong Zhang, Ying Yang, Zheng Li
Summary: A new quadruple FFA1/PPAR-alpha/gamma/delta agonist, ZLY18, with longer metabolic half-life and stronger lipid-lowering effects, has been discovered for the treatment of NAFLD and NASH. It also exhibits stronger regulation on genes related to lipid synthesis, oxidative stress, inflammation, and fibrosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Plant Sciences
Xin Pang, Yuan Cheng, Meiying Ruan, Qingjing Ye, Rongqing Wang, Zhuping Yao, Guozhi Zhou, Hongjian Wan
Summary: In this study, comprehensive comparative analyses of PAP genes were conducted, revealing the complex structures and potential functional diversification of PAP genes. The findings contribute to a better understanding of the function of SlPAP genes and the evolutionary relationships in plants.
Article
Biochemistry & Molecular Biology
Lianru Chen, Ya Chen, Bin Wang, Zhongcheng Yang, Zongyu Cai, Xuekun Wang, Lidan Sun, Zheng Li, Guangji Wang
Summary: Metabolic syndrome is a complex disease with limited efficacy in current pharmacological interventions. Indeglitazar, a pan-agonist targeting PPARs, shows therapeutic effects on diabetic and fatty liver models. However, its short half-life limits efficacy. To overcome this, deuterated derivatives were introduced to block beta-oxidation. I-1 exhibited strong glucose-lowering and liver improvement effects, and had stronger regulation effects on genes related to lipid metabolism, mitochondrial function, and oxidative stress compared to Indeglitazar.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Honghong Deng, Xingyu Long, Xi Wang, Yang Wang, Changqing Pang, Hui Xia, Dong Liang, Huifen Zhang, Xian Luo, Jin Wang, Xiulan Lv, Qunxian Deng
Summary: Plums are rich in bioactive phytochemical compounds, including vitamins, anthocyanins, and carotenoids, which have multiple potential health benefits. However, limited knowledge exists regarding the carotenoid profiles of plums. This study analyzed the total and individual carotenoid contents in the edible parts of ten plum cultivars, with the skin showing significantly higher carotenoid levels than the flesh in all cultivars. The major carotenoids detected were lutein, zeaxanthine, β-cryptoxanthin, α-carotene, and β-carotene, with lutein and β-carotene being the predominant constituents of the skin and flesh tissues, respectively. The expression of carotenoid biosynthetic genes was correlated with the carotenoid contents. Characterizing the carotenoid profiles and studying the variations in carotenoid biosynthetic gene expressions are important for genetic improvements in plums.
Article
Pediatrics
Li-Fang Ni, Ying Han, Shan-Shan Wang, Xiao-Jun Lin, Yu-Huan Wang, Hong-Tao Yan, Xin-Jun Yang
Summary: This study found that the expression changes of PPAR alpha/gamma and miR-27b were associated with non-GDM macrosomia in placenta. Further experiments confirmed that miR-27b was involved in the occurrence of non-GDM macrosomia by negatively regulating the expression of PPAR alpha/gamma protein.
PEDIATRIC RESEARCH
(2023)
Article
Biochemical Research Methods
Ting-Ting Ding, Ya-Ya Liu, Li-Ming Zhang, Jia-Rui Shi, Wei-Ren Xu, Shao-Yong Li, Xian-Chao Cheng
Summary: This study utilized pharmacophore modeling and molecular dynamics simulation to screen and obtain 9 new PPAR alpha/gamma agonists.
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
(2022)
Article
Chemistry, Medicinal
Leila Moradihaghgou, Reinhard Schneider, Bahram Maleki Zanjani, Taher Harkinezhad
Summary: This study focused on PPAR gamma as the target and used virtual screening to find potential drug compounds. Flavonoid compounds were filtered based on drug-likeness and ADMET strategies, and the candidates' binding modes to PPAR gamma were evaluated through docking and MD simulation. PharmMapper was used to identify potential targets, and the pharmacological network was constructed based on GO and KEGG pathway analysis. The results suggested that the selected compounds have sufficient drug-likeness and in silico bioactivity as PPAR gamma partial agonists.
MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Johanna Klughammer, Daria Romanovskaia, Amelie Nemc, Annika Posautz, Charlotte A. Seid, Linda C. Schuster, Melissa C. Keinath, Juan Sebastian Lugo Ramos, Lindsay Kosack, Ann Evankow, Dieter Printz, Stefanie Kirchberger, Bekir Erguener, Paul Datlinger, Nikolaus Fortelny, Christian Schmidl, Matthias Farlik, Kaja Skjaerven, Andreas Bergthaler, Miriam Liedvogel, Denise Thaller, Pamela A. Burger, Marcela Hermann, Martin Distel, Daniel L. Distel, Anna Kuebber-Heiss, Christoph Bock
Summary: This study maps DNA methylation in 535 vertebrates and 45 invertebrates and establishes a reference dataset for cross-species analysis. It quantifies the association between DNA methylation and genomic DNA sequence throughout vertebrate evolution and reveals a deeply conserved association of DNA methylation with tissue type. The study also identifies evolutionary changes in DNA methylation at gene promoters for orthologous genes.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Eun Young Kim, Jae Man Lee
Summary: This study reveals the impact of autophagy defects on the transactivation of PPAR alpha, which plays a key role in fasting-associated metabolisms. Autophagy defects lead to the activation of NRF2, an antioxidant transcription factor, which in turn blunts the function of PPAR alpha. These findings highlight the importance of basal autophagy for the function of PPAR alpha.
Article
Pharmacology & Pharmacy
Aynur Ekiciler, Wen Li Kelly Chen, Yan Bo, Alessandra Pugliano, Massimiliano Donzelli, Neil Parrott, Kenichi Umehara
Summary: This study successfully demonstrated a linear correlation between CYP3A4 mRNA induction potential and PXR activation in human hepatocytes. Based on this correlation, the magnitude of CYP3A4 mRNA induction for 71 internal compounds was predicted within 2-fold error for 64% of cases. Furthermore, the in vivo area under the curve reduction of probe CYP substrates was reasonably predicted for eight marketed drugs using a static net effect model.
DRUG METABOLISM AND DISPOSITION
(2023)
Article
Cell & Tissue Engineering
Yifan Wang, Qiang Zheng, Zhen Sun, Chenhua Wang, Jin Cen, Xinjie Zhang, Yan Jin, Baihua Wu, Tingting Yan, Ziyuan Wang, Qiuxia Gu, Xingyu Lv, Junjie Nan, Zhongyu Wu, Wenbin Sun, Guoyu Pan, Ludi Zhang, Lijian Hui, Xiujun Cai
Summary: Liver resection is the preferred treatment for primary liver cancers, but concerns about post-hepatectomy liver failure have limited the number of eligible patients. A bioartificial liver device using human-induced hepatocytes showed promising results in a PHLF model and in a small study of patients undergoing liver resection. These findings suggest that this treatment could potentially expand the population eligible for liver resection.
Article
Biochemistry & Molecular Biology
Lu Tang, Qiang Lin, Yanhong Zhang
Summary: This study revealed that TBT disrupts hepatic lipid homeostasis in seahorses by promoting lipid synthesis and inhibiting lipid droplet breakdown.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Article
Entomology
Johan Sebastian Portilla-Pulido, Ruth Mariela Castillo-Morales, Mario Alberto Baron-Rodriguez, Jonny Edward Duque, Stelia Carolina Mendez-Sanchez
JOURNAL OF MEDICAL ENTOMOLOGY
(2020)
Article
Chemistry, Medicinal
Kristina Forsch, Verena Schoening, Greta Marie Assmann, Christin Moser, Beate Siewert, Veronika Butterweck, Juergen Drewe
PHYTOTHERAPY RESEARCH
(2020)
Article
Biotechnology & Applied Microbiology
Aziza A. A. Adam, Aldo Jongejan, Perry D. Moerland, Vincent A. van der Mark, Ronald P. Oude Elferink, Robert A. F. M. Chamuleau, Ruurdtje Hoekstra
Article
Pharmacology & Pharmacy
Dianke Yu, Jing Chen, Si Chen, Lin Xu, Leihong Wu, Dongying Li, Jiao Luo, Yuan Jin, Yanjie Zhao, Bridgett Knox, William H. Tolleson, Xubing Wang, Lei Guo, Weida Tong, Baitang Ning
DRUG METABOLISM AND DISPOSITION
(2020)
Article
Environmental Sciences
Lin Yu, Hequn Li, Chi Zhang, Qiang Zhang, Jiabin Guo, Jin Li, Haitao Yuan, Lizhong Li, Paul Carmichael, Shuangqing Peng
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2020)
Article
Chemistry, Analytical
Lea Wagmann, Sascha K. Manier, Thomas P. Bambauer, Christina Felske, Niels Eckstein, Veit Flockerzi, Markus R. Meyer
JOURNAL OF ANALYTICAL TOXICOLOGY
(2020)
Review
Toxicology
Katrin Kreuzer, Falko Frenzel, Alfonso Lampen, Albert Braeuning, Linda Boehmert
JOURNAL OF APPLIED TOXICOLOGY
(2020)
Article
Pharmacology & Pharmacy
Deborah Crombez, Sebastien Delcambre, Denis Nonclercq, Luce Vander Elst, Sophie Laurent, Miriam Cnop, Robert N. Muller, Carmen Burtea
JOURNAL OF DRUG TARGETING
(2020)
Article
Cell & Tissue Engineering
Mattia Pasqua, Ulysse Pereira, Antonietta Messina, Claire de Lartigue, Pascale Vigneron, Anne Dubart-Kupperschmitt, Cecile Legallais
TISSUE ENGINEERING PART A
(2020)
Article
Pharmacology & Pharmacy
Marco E. Franco, Grace E. Sutherland, Maria T. Fernandez-Luna, Ramon Lavado
Article
Toxicology
Eva Gijbels, Vania Vilas-Boas, Pieter Annaert, Tamara Vanhaecke, Lindsey Devisscher, Mathieu Vinken
ARCHIVES OF TOXICOLOGY
(2020)
Article
Toxicology
Shuo Yang, Matthias Diem, Jakob D. H. Liu, Sebastiaan Wesseling, Jacques Vervoort, Chris Oostenbrink, Ivonne M. C. M. Rietjens
ARCHIVES OF TOXICOLOGY
(2020)
Article
Toxicology
Dongying Li, Leihong Wu, Bridgett Knox, Si Chen, William H. Tolleson, Fang Liu, Dianke Yu, Lei Guo, Weida Tong, Baitang Ning
ARCHIVES OF TOXICOLOGY
(2020)
Article
Toxicology
Anne-Cathrin Behr, Anna Kwiatkowski, Marcus Stahlman, Felix Florian Schmidt, Claudia Luckert, Albert Braeuning, Thorsten Buhrke
ARCHIVES OF TOXICOLOGY
(2020)
Article
Pharmacology & Pharmacy
Kyoko Ondo, Hiroshi Arakawa, Masataka Nakano, Tatsuki Fukami, Miki Nakajima
BIOCHEMICAL PHARMACOLOGY
(2020)