Article
Biochemistry & Molecular Biology
Shin-Hun Juang, Min-Tsang Hsieh, Pei-Ling Hsu, Ju-Ling Chen, Hui-Kang Liu, Fong-Pin Liang, Sheng-Chu Kuo, Chen-Yuan Chiu, Shing-Hwa Liu, Chen-Hsi Chou, Tian-Shung Wu, Hsin-Yi Hung
Summary: In the study, 6,7-diprenoxycoumarin was identified as the most effective CAR activator, with modifications at the 6 position and unsaturated chains generally beneficial. The research also indicated that mimicking natural occurring coumarins for modification shed light on CAR studies.
Article
Cell Biology
Fabiana Oliviero, Wendy Klement, Lucile Mary, Yannick Dauwe, Yannick Lippi, Claire Naylies, Veronique Gayrard, Nicola Marchi, Laila Mselli-Lakhal
Summary: Non-Alcoholic Fatty Liver Disease (NAFLD) is a common chronic liver disease, especially in obese individuals. This study suggests that the nuclear receptor CAR may play a role in the pathogenesis of NAFLD and could be a potential therapeutic target. In mice, deletion of CAR led to a NASH-like hepatic transcriptomic signature and astrogliosis in the hypothalamus of female mice.
Article
Pharmacology & Pharmacy
Congrong Niu, Bill Smith, Yurong Lai
Summary: This study characterized the gene induction by ligands of CAR and AhR in human hepatocytes, showing distinct effects on metabolizing enzyme and drug transporter genes. Different inducers had varying degrees of effects on specific genes, highlighting the importance of assessing transporter gene inductions alongside metabolizing enzyme genes.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sarah Da Won Bae, Romario Nguyen, Liang Qiao, Jacob George
Summary: CAR is a receptor that is predominantly expressed in the liver and interacts with key signaling pathways related to drug, energy, and bilirubin metabolism. While studies in animal models suggest a potential role of CAR in tumorigenesis, recent research has shown species differences and a possible tumor-suppressive role of CAR in liver cancer in humans. This review highlights the need for further exploration of CAR's role in human diseases, particularly cancers, with a focus on its emerging functions in liver cancer.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Endocrinology & Metabolism
Ye Feng, Dan Xu, Xinran Cai, Meishu Xu, Wojciech G. Garbacz, Songrong Ren, Michael J. Jurczak, Chaohui Yu, Hui Wang, Wen Xie
Summary: The study found that GDM is a key risk factor for future development of metabolic disease, and CAR could be a therapeutic target for managing metabolic diseases sensitized by GDM.
Article
Nutrition & Dietetics
Xuan Xiang, Houfu Wang, Wentao Zhou, Chenyu Wang, Peng Guan, Gang Xu, Qiang Zhao, Liuqin He, Yulong Yin, Tiejun Li
Summary: This study investigated the regulatory mechanism of different dietary levels of endogenous glutathione (GSH) supplementation on the intestinal barrier and antioxidant function in a paraquat-induced stress-weaned piglet model. The results showed that dietary 0.06% GSH supplementation improved the growth performance and reduced diarrhea rate of weaned piglets. GSH also protected against oxidative stress damage by regulating intestinal morphology, organelle, and permeability, as well as modulating antioxidant and anti-inflammatory gene expression.
Review
Neurosciences
Victor Fernandez-Duenas, Jordi Bonaventura, Ester Aso, Rafael Lujan, Sergi Ferre, Francisco Ciruela
Summary: G protein-coupled receptors (GPCRs) are the main membrane receptor proteins controlling brain activity and are targeted by drugs for neurological and neuropsychiatric disorders. GPCRs regulate neuronal function through homo- and heteromerization, and various techniques are used to study GPCR oligomerization in native tissue. The adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is used as an example to illustrate the implementation of these techniques in visualizing GPCR oligomers in the human brain under normal and pathological conditions. GPCR oligomerization may play a role in the pathophysiology of neurological and neuropsychiatric disorders.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Frances M. Bashore, Caroline A. Foley, Han Wee Ong, Justin M. Rectenwald, Ronan P. Hanley, Jacqueline L. Norris-Drouin, Stephanie H. Cholensky, Christine A. Mills, Kenneth H. Pearce, Laura E. Herring, Dmitri Kireev, Stephen Frye, Lindsey I. James
Summary: Bivalent chemical degraders, known as PROTACs, are an effective strategy for targeting cancer proteins. However, their physicochemical properties and optimization for efficient degradation are often unpredictable.
ACS CHEMICAL BIOLOGY
(2023)
Review
Cell Biology
Yiwei Zhou, Jiyong Meng, Chanjuan Xu, Jianfeng Liu
Summary: G protein-coupled receptors (GPCRs) are a large membrane protein family involved in physiological and pathological activities, and various sensors have been developed to monitor conformational changes for high-throughput drug screening purposes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Leonida Rakateli, Rosanna Huchzermeier, Emiel P. C. van der Vorst
Summary: Xenobiotic receptors play a crucial role in both chemical sensing and detoxification as well as lipid metabolism regulation, particularly in relation to dyslipidemia.
Article
Dermatology
Baochang Lai, Xinya Xie, Fan Li, Qi Cui, Erle Dang, Wenhuan Luo, Ning Wang, Yan Zheng, Gang Wang, Lei Xiao, Nanping Wang
Summary: The study demonstrates that CAR plays a pathogenic role in psoriasis and has the potential to be a target for its treatment. Xenobiotics and proinflammatory cytokines affect the expression of CAR and its target genes, further promoting the development of psoriatic skin lesions.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Maike Gaehrs, Dieter Schrenk
Summary: NDL-PCBs can suppress UV-induced apoptosis in rat hepatocytes by activating CAR and PXR, and the effects on apoptosis by CAR or PXR activators are specific to CAR or PXR.
Article
Food Science & Technology
Takumi Sato, Ryota Shizu, Yoshie Miura, Takuomi Hosaka, Yuichiro Kanno, Takamitsu Sasaki, Kouichi Yoshinari
Summary: This study identified possible direct and indirect activators of rCAR by measuring Cyp2b1 mRNA levels and performing reporter assays. It demonstrated the usefulness of these methods in evaluating rCAR activation by chemicals.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mireia Lopez-Riera, Rebeca Ortega, Luisa Hueso, Maria Carmen Montesinos, Mari Carmen Gomez-Cabrera, Maria Jesus Sanz, Jose T. Real, Laura Piqueras
Summary: This study demonstrates that CAR agonists can inhibit the early inflammatory response that precedes atherosclerosis by targeting various steps in the leukocyte recruitment cascade. This suggests that CAR agonists may serve as a new therapeutic approach to control inflammation associated with cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Bhavna Sharma, Bhavya Sethi, Shashank Kumar, Raju Poddar, Amit Prasad, Shubha Rani Sharma
Summary: In this study, the interactions between scoparone and CAR were analyzed through computational simulation. It was found that scoparone can stably interact with CAR, thus activating CAR and preventing gallstone formation. These results provide valuable insights for further in vivo studies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Analytical
Hana Sklenarova, Michaela Rosecka, Burkhard Horstkotte, Petr Pavek, Manuel Miro, Petr Solich
Summary: A new design of permeation module based on 3D printing was developed to monitor the interaction of exogenic compounds with cell membrane transporters in real-time. The module was shown to be effective in studying the activity of the P-glycoprotein membrane transporter and the inhibitory effect of verapamil, demonstrating enhanced Rho123 transfer and accumulation into cells. This 3D-printed module shortened permeation testing time and allowed for evaluation based on kinetic profiles, showing potential for rapid and accurate testing in drug development.
ANALYTICA CHIMICA ACTA
(2021)
Review
Nutrition & Dietetics
Alejandro Carazo, Katerina Macakova, Katerina Matousova, Lenka Kujovska Krcmova, Michele Protti, Premysl Mladenka
Summary: Vitamin A is a vital micronutrient found in human diet from animal-based products and fruits and vegetables. It plays a key role in physiological functions and can be metabolized into biologically active forms in the human body. Research focuses on a comprehensive understanding of vitamin A from sources to physiological functions to potential toxicity.
Article
Pharmacology & Pharmacy
Samvel N. Sirakanyan, Marcel Hrubsa, Domenico Spinelli, Patricia Dias, Victor Kartsev, Alejandro Carazo, Anush A. Hovakimyan, Jana Pourova, Elmira K. Hakobyan, Jana Karlickova, Shamima Parvin, Jaka Fadraersada, Katerina Macakova, Athina Geronikaki, Premysl Mladenka
Summary: In this study, a series of 6-oxopyrano[3,4-c]pyridines were synthesized and the 8-methyl derivative (3a) was found to be a potent inhibitor of platelet aggregation with additional vasodilatory activity.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2022)
Review
Nutrition & Dietetics
Premysl Mladenka, Katerina Macakova, Lenka Kujovska Krcmova, Lenka Javorska, Kristyna Mrstna, Alejandro Carazo, Michele Protti, Fernando Remiao, Lucie Novakova
Summary: Vitamin K is not only involved in blood coagulation, but also in the maturation of proteins and physiological processes in bones. Research has suggested a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases, but current knowledge is insufficient to make a decisive conclusion.
Article
Biochemistry & Molecular Biology
Marcel Hrubsa, Raul Alva, Mst Shamima Parvin, Katerina Macakova, Jana Karlickova, Jaka Fadraersada, Lukas Konecny, Monika Moravcova, Alejandro Carazo, Premysl Mladenka
Summary: Flavonoids have positive cardiovascular effects, and one of its metabolites, 4-methylcatechol, is a potent antiplatelet compound. In this study, the activity of 22 compounds, including 4-methylcatechol and its derivatives, were compared. Results showed that 17 compounds were highly active in inhibiting platelet aggregation, with 7 of them having an IC50 below 3 mu M. These compounds showed no toxicity to erythrocytes or significant effects on blood coagulation.
Article
Chemistry, Medicinal
Marcel Hrubsa, Khondekar Nurjamal, Alejandro Carazo, Nayana Nayek, Jana Karlickova, Lenka Applova, Indrajit Karmakar, Shamima Parvin, Jaka Fadraersada, Katerina Macakova, Premysl Mladenka, Goutam Brahmachari
Summary: In this study, the antiplatelet and anticoagulation properties of selected compounds were examined. Four out of 34 tested compounds showed equal or greater activity than the standard antiplatelet drug ASA. These compounds achieved their effects through antagonism at thromboxane receptors. The most active compound, 2-N, was 4-5 times more potent than ASA and holds promise for the development of novel antiplatelet drugs.
MEDICINAL CHEMISTRY
(2022)
Article
Food Science & Technology
Mst Shamima Parvin, Marcel Hrubsa, Jaka Fadraersada, Alejandro Carazo, Jana Karlickova, Lucie Cahlikova, Jakub Chlebek, Katerina Macakova, Premysl Mladenka
Summary: Isoquinoline alkaloids exhibit antiplatelet effects mainly at high concentrations, and bulbocapnine is a promising antiplatelet molecule.
Review
Hematology
Alejandro Carazo, Marcel Hrubsa, Lukas Konecny, Pavel Skorepa, Marketa Paclikova, Frantisek Musil, Jana Karlickova, Lenka Javorska, Katerina Matousova, Lenka Kujovska Krcmova, Mst Shamima Parvin, Alena Smahelova, Vladimir Blaha, Premysl Mladenka
Summary: The process of platelet aggregation is influenced by factors such as sex and age. A literature review and a local study found sex-related differences in platelet aggregation, with women showing higher aggregation responses to certain agonists and lower benefit from inhibitors. Age also affects the aggregatory responses to different triggers, and further studies are needed to understand the biological importance of these differences.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2023)
Meeting Abstract
Toxicology
R. Alva Gallegos, A. Carazo, P. Mladenka
TOXICOLOGY LETTERS
(2022)
Review
Cell Biology
Rajamanikkam Kamaraj, Martin Drastik, Jana Maixnerova, Petr Pavek
Summary: This article summarizes the allosteric modulation of PXR and the exploration of novel allosteric sites. The identified allosteric sites of PXR provide new insights into the development of safe and efficient allosteric modulators, which may become promising targets for treating chronic metabolic diseases and some cancers.
Article
Environmental Sciences
Vaclav Tvrdy, Patricia Dias, Iveta Nejmanova, Alejandro Carazo, Eduard Jirkovsky, Jana Pourova, Jaka Fadraersada, Monika Moravcova, Lucija Peterlin Masic, Marija Sollner Dolenc, Premysl Mladenka
Summary: The human population is regularly exposed to bisphenols, which are potentially toxic. This study aimed to test the effects of 14 bisphenols on the cardiovascular system and compare their effects in different settings. Most of the tested bisphenols could relax rat aorta, but their potency varied significantly.
Article
Nutrition & Dietetics
Marcel Hrubsa, Lukas Konecny, Marketa Paclikova, Mst Shamima Parvin, Pavel Skorepa, Frantisek Musil, Jana Karlickova, Lenka Javorska, Katerina Matousova, Lenka Kujovska Krcmova, Alejandro Carazo, Alena Smahelova, Vladimir Blaha, Premysl Mladenka
Summary: A polyphenol-rich diet has positive effects on cardiovascular health, and metabolites formed by human microbiota could be responsible for this effect. 4-MC, a small phenolic metabolite, was shown to be more potent than acetylsalicylic acid in reducing platelet aggregation, and the mechanism of its action was identified as interference with the coupling of cyclooxygenase and thromboxane synthase.
Article
Chemistry, Medicinal
Miroslav Sisa, Lukas Konecny, Veronika Temml, Alejandro Carazo, Premysl Mladenka, Premysl Landa
Summary: In this study, a set of compounds structurally mimicking selective COX-1 inhibitors were designed and synthesized. The newly synthesized compounds exhibited remarkable selectivity and activity in enzymatic in vitro assays, with compound 10a showing comparable activity to SC-560 and even greater selectivity. Cell-based antiplatelet assays further confirmed this activity.
ARCHIV DER PHARMAZIE
(2023)
Article
Environmental Sciences
Raul Alva-Gallegos, Alejandro Carazo, Premysl Mladenka
Summary: This review aims to summarize the available knowledge on products derived from human industrial activity and other xenobiotics that interact with the estrogen receptor (ER). These chemicals, known as endocrine disruptors, can affect various physiological processes involving ER. However, most of the studies focus on individual compound testing, lacking in vivo models and assessments of xenobiotic combinations which better resemble real circumstances.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2023)
Article
Nutrition & Dietetics
Lukas Konecny, Marcel Hrubsa, Jana Karlickova, Alejandro Carazo, Lenka Javorska, Katerina Matousova, Lenka Kujovska Krcmova, Alena Smahelova, Vladimir Blaha, Milan Blaha, Premysl Mladenka
Summary: This study analyzed the antiplatelet effect of 4-MC in FH patients and compared its impact on two FH treatment modalities. The results showed that 4-MC had a stronger inhibitory effect on collagen-induced platelet aggregation in FH patients compared to the healthy control group. The study also found that apheresis improved the inhibitory effect of 4-MC on platelet aggregation, and patients treated with apheresis and pretreated with 4-MC had lower platelet aggregability compared to those solely treated with PCKS9Ab. This study confirmed the suitability of 4-MC as a promising antiplatelet agent and demonstrated its effect in patients with a genetic metabolic disease for the first time.