Article
Endocrinology & Metabolism
Fizalah Kawoosa, Zafar A. Shah, Shariq R. Masoodi, Asif Amin, Roohi Rasool, Khalid M. Fazili, Abid Hamid Dar, Asif Lone, Samir ul Bashir
Summary: This study reveals the crucial role of OCT-1 in the transport of metformin and suggests that genetic variations in OCT1 may influence the transport of metformin, thereby affecting treatment response in patients.
BMC ENDOCRINE DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Kyra-Elisa Maria Redeker, Ole Jensen, Lukas Gebauer, Marleen Julia Meyer-Toennies, Juergen Brockmoeller
Summary: The human organic cation transporter 1 (OCT1) plays a crucial role in hepatic uptake of organic cations. Recent studies suggest that OCT1 can also transport neutral and anionic substrates, but with lower activity. Understanding the substrate spectrum and transport mechanisms of OCT1, including organic anions, is essential for a comprehensive understanding of its clinical relevance.
Article
Biochemistry & Molecular Biology
David A. Doetsch, Salim Ansari, Ole Jensen, Lukas Gebauer, Christof Duecker, Jurgen Brockmoeller, Alexandra Sachkova
Summary: This study characterized the substrate spectrum of a proton-organic cation (H + OC) antiporter, which is responsible for transporting organic cations through membranes. Using hCMEC/D3 cells as a model, the researchers examined the uptake of 72 drugs and identified 37 of them as good substrates of the H + OC antiporter. Further analysis showed that the substrates had specific characteristics, such as being more hydrophobic and having a lower topological polar surface area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
So Ra Choi, Hee Myeong Wang, Min Hyeon Shin, Hyun-Suk Lim
Summary: An SRC-1 degrader was developed to selectively degrade cellular SRC-1, effectively reducing its levels and suppressing cancer cell migration and invasion by mimicking an unfolded state of SRC-1 through a hydrophobic tagging strategy. This novel approach could have wide applications in developing peptide-based protein degraders with enhanced cellular activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Christoph Wenzel, Marek Drozdzik, Stefan Oswald
Summary: Intestinal transporter proteins play a crucial role in the pharmacokinetics and efficacy/safety of orally administered drugs, particularly ATP-binding cassette transporters. While information on intestinal uptake carriers is limited, recent studies suggest organic cation transporter 1 may function as an elimination pathway for cationic compounds in the human intestine.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Plant Sciences
Lu Han, Xiaohua Wu, Xinyu Zhang, Kailin Hou, Hongshan Zhang, Chenjia Shen
Summary: In this study, a cation-efflux gene named BjCET1 was cloned and characterized in Brassica juncea. The results suggest that BjCET1 plays an essential role in heavy metal ion homeostasis and hyper-accumulation.
Article
Pharmacology & Pharmacy
Lukas Gebauer, N. Arul Murugan, Ole Jensen, Juergen Brockmoeller, Muhammad Rafehi
Summary: Stereoselectivity plays an important role in drug membrane transport, but its impact is still not well understood. This study investigated the stereoselective effects of fenoterol enantiomers in cellular uptake, and proposed possible molecular explanations through computational modeling and experimental validation. The results suggest that fenoterol enantiomers bind to distinct binding sites in OCT1 and OCT2, leading to the observed stereoselectivity differences.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Masahiro Izutsu, Takanori Domoto, Shingo Kamoshida, Hiroyuki Ohsaki, Hiroshi Matsuoka, Yusuke Umeki, Kazuya Shiogama, Masaya Hirayama, Koichi Suda, Ichiro Uyama
Summary: The study suggests that the expression of p53(MT-ex) or OCT1(Low) in pretreatment biopsy specimens may be potential predictors of poor response to preoperative chemotherapy with CF-based regimens in ESCC, although specificity needs improvement.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Chemistry, Analytical
Abdulaziz Ahmed A. Saad, Fan Zhang, Moath Refat, Eyad Abdulwhab H. Mohammed, Mingkang Zhang, Yuyue Chen, Bandar Al Hamyari, Jameel Alafifi, Xin'an Wu
Summary: This study evaluated the effect of tamsulosin on the pharmacokinetics of metformin and found that tamsulosin can increase the systemic exposure and reduce excretion of metformin, possibly through inhibiting Oct2 and Mate1-mediated transport.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Tatsuya Kawasaki, Chisa Kaneko, Ryosuke Nakanishi, Yoshinori Moriyama, Tomohiro Nabekura
Summary: This study investigated the transport characteristics of amiloride by human MATE1 and found that MATE1 transported amiloride at an extracellular pH of 7.4, with saturated uptake and a bell-shaped pH profile. Additionally, the study discovered that pyrimethamine and fampridine exhibited strong inhibition on MATE1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Camila A. Cotrim, Russell J. Jarrott, Andrew E. Whitten, Hassanul G. Choudhury, David Drew, Jennifer L. Martin
Summary: In this study, it was demonstrated that human ZnT1 and its variant can be expressed and purified in yeast cells, with the purified hZnT1 variant showing Zn2+/H+ antiporter activity. Additionally, the soluble C-terminal domain of hZnT1 was successfully expressed, purified, and characterized in a bacterial expression system, showing an increase in melting temperature at acidic pH and forming a dimer in solution based on small-angle X-ray scattering analysis.
FRONTIERS IN CHEMISTRY
(2021)
Article
Cell Biology
Joel P. Wiener, Sindy Desire, Viktor Garliyev, Nicholas Lyssenko III, Domenico Pratico, Nicholas N. Lyssenko
Summary: ABCA7 is a major risk factor for Alzheimer's disease and its expression is regulated by cholesterol and pro-inflammatory cytokines. Depletion of cholesterol can decrease ABCA7 expression in certain neural cells, but not in neurons. IL-1 beta and TNF alpha can reduce ABCA7 expression in microglia.
Article
Biochemistry & Molecular Biology
Liang Zhou, Fei Wang, Xiudao Song, Min Shi, Guodiang Liang, Lurong Zhang, Fei Huang, Guorong Jiang
Summary: 3DG reduces low glucose-induced GLP-1 secretion in part through reduction of SGLT1 expression.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Abdulaziz Ahmed A. Saad, Fan Zhang, Eyad Abdulwhab H. Mohammed, Xin'an Wu
Summary: OCT2 and MATE1/2-K are crucial transporters in the kidneys that play a significant role in drug metabolism, therapeutic efficacy, and toxicity. Understanding the localization and functionality of these transporters is essential for preventing or enhancing drug-induced nephrotoxicity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(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
Toxicology
Tomas Smutny, Veronika Bernhauerova, Lucie Smutna, Jurjen Duintjer Tebbens, Petr Pavek
Summary: This study utilized 3D PHHs to investigate the time-expression profiles of PXR-controlled genes during rifampicin treatment, revealing diverse expression patterns among different genes, some of which were influenced by rifampicin concentration. The results highlight the importance of long-term time-expression profiling in 3D PHHs for studying PXR target genes.
ARCHIVES OF TOXICOLOGY
(2022)
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.
Article
Biochemical Research Methods
Pavel Barta, Rajamanikkam Kamaraj, Monika Kucharova, Zbynek Novy, Milos Petrik, Katerina Bendova, Marian Hajduch, Petr Pavek, Frantisek Trejtnar
Summary: As angiogenesis plays a crucial role in tumor growth and metastasis, it is important to target the vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) for diagnostic and therapeutic purposes. In this study, two peptides labeled with PET emitters were prepared and tested as new imaging agents for tumor angiogenesis. The results showed that both peptides had good binding affinity to VEGFRs in cancer cells and exhibited potential for imaging.
BIOCONJUGATE CHEMISTRY
(2022)
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)
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
Chemistry, Medicinal
Martin Kratky, Klara Konecna, Adela Simkova, Ondrej Jandourek, Jana Maixnerova, Jirina Stolarikova, Marcela Vejsova, Barbora Voxova, Frantisek Trejtnar, Jarmila Vinsova
Summary: Twenty-one mafenide-based compounds were synthesized and tested for antimicrobial activity, showing promising efficacy against various pathogens including superbugs. Most imines of mafenide were bactericidal and retained activity against drug-resistant strains. The most promising drug candidates have iodinated salicylidene and 5-nitrofuran/thiophene-methylidene scaffolds.
FUTURE MEDICINAL CHEMISTRY
(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.
