Article
Cell Biology
David Czimer, Klaudia Porok, Daniel Csete, Zsolt Gyure, Viktoria Lavro, Krisztina Fulop, Zelin Chen, Hella Gyergyak, Gabor E. Tusnady, Shawn M. Burgess, Attila Mocsai, Andras Varadi, Mate Varga
Summary: Calcification is a significant health issue associated with aging, cancer, and autoimmune diseases, with both environmental and genetic factors at play. Understanding the phenomenon is essential for developing effective therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease without a cure, but research shows that zebrafish could serve as a new model for studying the disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ricarda Pluemers, Christopher Lindenkamp, Michel Robin Osterhage, Cornelius Knabbe, Doris Hendig
Summary: Ectopic calcification and dysregulated extracellular matrix remodeling are prominent features of pseudoxanthoma elasticum (PXE). ABCC6 mutations are associated with the disease. Overexpression of matrix metalloproteinases (MMPs) on human chromosome 11q21-23 and murine chromosome 9 was found in PXE patients and Abcc6(-/-) mice. The MMP inhibitor Marimastat was shown to affect calcification, indicating a correlation between ECM remodeling, MMP expression, and calcification in PXE pathobiology.
Article
Cardiac & Cardiovascular Systems
Jonas W. Bartstra, Sara Risseeuw, Pim A. de Jong, Bram van Os, Lianne Kalsbeek, Chris Mol, Annette F. Baas, Shana Verschuere, Olivier Vanakker, Ralph J. Florijn, Jeroen Hendrikse, Willem Mali, Saskia Imhof, Jeannette Ossewaarde-van Norel, Redmer van Leeuwen, Wilko Spiering
Summary: The study revealed that PXE patients with a mixed genotype showed less severe arterial and ophthalmological phenotypes compared to patients with two truncating variants in the ABCC6 gene. Further research into environmental and genetic modifiers may help explain the unexplained phenotypic variability.
Article
Dermatology
Eszter Kozak, Krisztina Fulop, Natalia Tokesi, Nidhi Rao, Qiaoli Li, Sharon F. Terry, Jouni Uitto, Xiaoming Zhang, Cyrus Becker, Andras Varadi, Viola Pomozi
Summary: PXE is a rare hereditary multisystem disorder affecting elastic fibers in the skin, eyes, and cardiovascular system. Research has shown that orally administered pyrophosphate compounds can inhibit ectopic calcification, providing a crucial foundation for potential clinical trials involving oral PPi in the future.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Medicine, General & Internal
Federica Boraldi, Francesco Demetrio Lofaro, Lorena Losi, Daniela Quaglino
Summary: The study found that fragmented elastic fibers were prevalent in clinically unaffected skin of PXE patients, while calcified fibers were rarely observed. Both p-SMAD1/5/8 and p-SMAD2/3 were activated in both affected and unaffected skin.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Dermatology
Hongbin Luo, Masoomeh Faghankhani, Yi Cao, Jouni Uitto, Qiaoli Li
Summary: In the past two decades, significant progress has been made in understanding the molecular basis and pathomechanistic details of pseudoxanthoma elasticum (PXE). Genetic modifiers have been identified to explain the phenotypic heterogeneity of PXE, in addition to pathogenic variants in the ABCC6 gene. The genetic complexity of PXE is further complicated by PXE-like phenotypes caused by variants in other ectopic mineralization-associated genes.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Medicine, General & Internal
Lukas Nollet, Matthias Van Gils, Suzanne Fischer, Laurence Campens, Swapna Karthik, Andreas Pasch, Julie De Zaeytijd, Bart P. Leroy, Daniel Devos, Tine De Backer, Paul J. Coucke, Olivier M. Vanakker
Summary: This study evaluated the potential of serum calcification propensity T50 as a biomarker for disease severity in patients with pseudoxanthoma elasticum (PXE). The results showed that shorter serum T50 was associated with a more severe phenotype in PXE patients. This suggests that serum T50 might be a clinically relevant biomarker in PXE, which could be of importance for future therapeutic trials.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Medicine, General & Internal
Hongbin Luo, Qiaoli Li, Yi Cao, Jouni Uitto
Summary: Pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC) are heritable ectopic mineralization disorders characterized by reduced plasma levels of inorganic pyrophosphate (PPi). Current research efforts aim to develop treatments for these conditions by normalizing PPi plasma levels or preventing calcium hydroxyapatite deposition independently of PPi.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Elise Bouderlique, Ellie Tang, Jeremy Zaworski, Amelie Coudert, Dominique Bazin, Ferenc Borondics, Jean-Philippe Haymann, Georges Leftheriotis, Ludovic Martin, Michel Daudon, Emmanuel Letavernier
Summary: This study found that vitamin D and calcium supplementation accelerate vascular calcification in a murine model of pseudoxanthoma elasticum (PXE). These results sound a warning regarding the use of these supplementations in PXE patients and patients with low systemic pyrophosphate levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Raphael Lee, Mark Lebwohl
Summary: There is no inherent risk of obstetric complications for PXE pregnancies, and patients do not need to be advised against becoming pregnant as previously suggested. PXE-related pregnancies are unremarkable to the mother's wellbeing, and fetal complications are few, if any.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Dermatology
Laura Atzori, Caterina Ferreli, Luca Pilloni, Franco Rongioletti
Summary: PDE is an acquired, rare elastic tissue disorder characterized by yellow papules on the neck, with no systemic implications and only of aesthetic concern. The etiology is likely multifactorial, and diagnosis relies on histopathology examination.
CLINICS IN DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Elise Bouderlique, Lukas Nollet, Emmanuel Letavernier, Olivier M. Vanakker
Summary: In this proof-of-concept study, the anticalcifying effect of minocycline was validated in Abcc6(-/-) mice for the first time, suggesting it as a promising therapeutic compound for PXE patients due to its favorable safety profile in humans and low cost as a generic drug.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Francesco Demetrio Lofaro, Dario Pasquale Mucciolo, Vittoria Murro, Laura Pavese, Daniela Quaglino, Federica Boraldi
Summary: Next-generation sequencing approach can identify rare variants associated with PXE, avoiding invasive skin biopsy and expensive, time-consuming diagnostic procedures. This method helps expand and deepen understanding of this complex rare disease, improve patient counseling, and has the future potential for personalized medicine.
FRONTIERS IN MEDICINE
(2021)
Review
Health Care Sciences & Services
Kenji Kawai, Yu Sato, Rika Kawakami, Atsushi Sakamoto, Anne Cornelissen, Masayuki Mori, Saikat Ghosh, Robert Kutys, Renu Virmani, Aloke Finn
Summary: It is rare to see evidence of arterial calcification in infants and children, and when detected, genetic disorders of calcium metabolism should be suspected. Generalized arterial calcification of infancy (GACI) is a hereditary disease characterized by severe arterial calcification, mostly involving the media with marked intimal proliferation and ectopic mineralization. ENPP1 and ABCC6 gene variants are associated with the disease, with higher mortality in subjects carrying ENPP1 variants. Overall mortality in individuals with GACI is high, and there is currently no ideal therapy, but gene-targeted treatments are being developed.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2022)
Article
Genetics & Heredity
Carlos R. Ferreira, Mary E. Hackbarth, Shira G. Ziegler, Kristen S. Pan, Mary S. Roberts, Douglas R. Rosing, Margaret S. Whelpley, Joy C. Bryant, Ellen F. Macnamara, Sisi Wang, Kerstin Mueller, Iris R. Hartley, Emily Y. Chew, Timothy E. Corden, Christina M. Jacobsen, Ingrid A. Holm, Frank Rutsch, Esra Dikoglu, Marcus Y. Chen, M. Zulf Mughal, Michael A. Levine, Rachel I. Gafni, William A. Gahl
Summary: Generalized arterial calcification of infancy (GACI) is usually caused by deficiency of ENPP1, and the natural history of GACI survivors has not been established. Out of 20 subjects, 16 presented with arterial calcifications, but only 5 had residual involvement at the time of evaluation.
GENETICS IN MEDICINE
(2021)
Article
Chemistry, Medicinal
Alzbeta Tuerkova, Orsolya Ungvari, Reka Laczko-Rigo, Erzsebet Mernyak, Gergely Szakacs, Csilla Ozvegy-Laczka, Barbara Zdrazil
Summary: This study focuses on hepatic organic anion transporting polypeptides (OATPs) and their interactions with drugs and natural substrates. Computational methods were used to establish structural models for hepatic OATPs and investigate the binding modes of steroid analogs in these transporters. Important structural determinants conferring shared and distinct binding patterns of steroid analogs in the OATPs were identified in this comparative study.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Endocrinology & Metabolism
Flora Szeri, Fatemeh Niaziorimi, Sylvia Donnelly, Nishat Fariha, Mariia Tertyshnaia, Drithi Patel, Stefan Lundkvist, Koen van de Wetering
Summary: The plasma membrane protein ANKH regulates pathological mineralization of joints by controlling extracellular levels of the mineralization inhibitor PPi. Recent research shows that ANKH overexpression results in the release of large amounts of NTPs, primarily ATP, into the culture medium. This ATP is then converted into PPi and AMP by the enzyme ENPP1. The study suggests that ANKH may not only transport PPi but also release it directly.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Mathematics, Interdisciplinary Applications
Levente Kovacs, Bence Czako, Mate Siket, Tamas Ferenci, Andras Furedi, Balazs Gombos, Gergely Szakacs, Daniel Andras Drexler
Summary: An algorithm for optimizing cancer therapy using control engineering approach is proposed and tested in a mouse model. The results demonstrate that remission can be induced within a 28-day interval using the algorithm.
Article
Chemistry, Medicinal
Alzbeta Tuerkova, Brandon J. Bongers, Ulf Norinder, Orsolya Ungvari, Virag Szekely, Andrey Tarnovskiy, Gergely Szakacs, Csilla Ozvegy-Laczka, Gerard J. P. van Westen, Barbara Zdrazil
Summary: The integration of statistical learning methods with structure-based modeling approaches is an effective strategy to identify novel lead compounds in drug discovery. In this study, a consensus virtual screening approach combined with molecular docking was used to discover highly active novel inhibitors for hepatic OATPs. The structural differences in ligand binding to the three transporters were explained through structural comparison of the detected binding sites and docking poses.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Veronika F. S. Pape, Roberta Palko, Szilard Toth, Miklos J. Szabo, Judit Sessler, Gyorgy Dorman, Eva A. . Enyedy, Tibor Soos, Istvan Szatmari, Gergely Szakacs
Summary: This study investigates the chemical space around 8-hydroxyquinoline-derived Mannich bases to identify compounds with MDR-selective toxicity in cancer cells. The experimental pKa values of donor atom moieties were found to strongly influence the MDR-selective anticancer activity of the compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Petra R. Varga, Alexandra Belovics, Peter Bagi, Szilard Toth, Gergely Szakacs, Szilvia Bosze, Rita Szabo, Laszlo Drahos, Gyorgy Keglevich
Summary: An efficient method utilizing acyl chlorides as reagents was developed for the acylation of hindered hydroxy groups in dialkyl alpha-hydroxybenzylphosphonates. The reaction did not require a catalyst and exhibited good optical purity. Furthermore, benzoylation of the alpha-hydroxy group was identified as a moiety that increased anticancer cytotoxicity and showed potential in multidrug resistant cancer cell lines.
Article
Biochemistry & Molecular Biology
Szonja Polett Posa, Gyula Dargo, Sandor Nagy, Peter Kisszekelyi, Zsofia Garadi, Lilla Hamori, Gergely Szakacs, Jozsef Kupai, Szilard Toth
Summary: This study evaluated the anticancer activity of 13 cinchona alkaloid organocatalysts and found that modifying quinine decreased cell inhibition values. Some derivatives showed expulsion effects on multidrug resistant cells.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Valeria Dekay, Edina Karai, Andras Fueredi, Kornelia Szebenyi, Gergely Szakacs, Peter Vajdovich
Summary: This study investigates the relationship between clinical outcomes and P-gp activity in tumor cells of canine B-cell lymphoma patients. The results show that the P-gp activity measured at diagnosis is not predictive of therapy outcome. This highlights the complexity of clinical drug resistance mechanisms.
Article
Genetics & Heredity
Flora Szeri, Agnes Miko, Nastassia Navasiolava, Ambrus Kaposi, Shana Verschuere, Beatrix Molnar, Qiaoli Li, Sharon F. Terry, Federica Boraldi, Jouni Uitto, Koen van de Wetering, Ludovic Martin, Daniela Quaglino, Olivier M. Vanakker, Kalman Tory, Tamas Aranyi
Summary: Incomplete penetrance is a source of heterogeneity in pseudoxanthoma elasticum. Two incomplete penetrant pathogenic variants were identified, but they are only deleterious when a yet unknown interacting partner of ABCC6 is mutated simultaneously.
Article
Biochemical Research Methods
Stefan Lundkvist, Fatemeh Niaziorimi, Flora Szeri, Matthew Caffet, Sharon F. Terry, Gunnar Johansson, Robert S. Jansen, Koen van de Wetering
Summary: Inorganic pyrophosphate (PPi) is a crucial regulator of extracellular mineralization, but there is currently no reliable assay for its quantification. In this study, we report a new and robust assay that converts PPi into ATP and quantifies it using firefly luciferase-based bioluminescence. The assay shows high sensitivity, precision, and accuracy, and outperforms currently available assays.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tamas Pivarcsik, Vivien Posa, Hilda Kovacs, Nora May, Gabriella Spengler, Szonja P. Posa, Szilard Toth, Zeinab Nezafat Yazdi, Csilla Ozvegy-Laczka, Imre Ugrai, Istvan Szatmari, Gergely Szakacs, Eva A. Enyedy
Summary: This article investigates a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(eta(5)-C5Me5) and Ru(eta(6)-p-cymene) complexes, which have excellent solubility in water and show inhibitory effects on sensitive and multidrug-resistant cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Evelyn Incze, Katalin Mango, Ferenc Fekete, Adam Ferenc Kiss, Adam Poti, Tuende Harko, Judit Moldvay, David Szuts, Katalin Monostory
Summary: Resistance to anticancer agents is a major problem in tumor therapy, and genetic polymorphisms and copy number alterations of drug-metabolizing enzymes contribute to the development of resistance. A high-throughput qPCR-based method was used to detect CYP copy number alterations in tumors, and the altered copy numbers of specific CYP genes were associated with non-responder patients. This method could be an alternative to next-generation sequencing and provide a potential biomarker for therapy-resistant tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Klara Farkas, Norbert Kiss, Viktoria Szabo, Miklos Resch, Rita Vamos, Agnes Borbandy, Ilona Nagy Aniko, Astrid Apor, Tamas Aranyi, Flora Szeri, Norbert Wikonkal, Zsolt Nagy Zoltan, Bela Merkely, Marta Medvecz
Summary: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder caused by ABCC6 gene mutations. It leads to ectopic mineralization and deposits of calcium-salt crystals in the skin, eyes, and blood vessels. The clinical symptoms are diverse and require collaboration between multiple specialists for accurate diagnosis and management. Early diagnosis and coordination of care are crucial for optimal patient outcomes.
Article
Chemistry, Inorganic & Nuclear
Janos P. Meszaros, Veronika F. S. Pape, Gergely Szakacs, Gabor Nemeti, Mark Denes, Tamas Holczbauer, Nora V. May, Eva A. Enyedy
Summary: A series of half-sandwich polypyridyl complexes were synthesized and compared for their structural, cytotoxic, and aqueous solution behavior. Introduction of methyl groups near coordinating nitrogen atoms affected steric congestion and changed ligand plane angles. The complexes showed high stability in solution, with Ru complexes susceptible to slow, irreversible decomposition in light exposure.
DALTON TRANSACTIONS
(2021)
Article
Optics
Mengyang Liu, Abigail J. Deloria, Richard Haindl, Qian Li, Gergely Szakacs, Agnes Csiszar, Stefan Schrittwieser, Paul Muellner, Rainer Hainberger, Beatriz Pelaz, Ester Polo, Pablo Del Pino, Antti Penttinen, Mircea Guina, Tapio Niemi, Kristen Meiburger, Filippo Molinari, Christian Menhard, Judith Heidelin, Volker Andresen, Douwe Geuzebroek, Wolfgang Drexler
Summary: This project aims to reveal drug tolerant persister cells in cancer and develop new technologies to improve detection methods and enhance the accuracy and sensitivity of imaging systems through interdisciplinary collaboration.
JOURNAL OF PHYSICS-PHOTONICS
(2021)