@article{MTMT:34827426, title = {Past and future of an IMI-PharmaTrain (IMI-PhT)-initiated multinational pharmaceutical medicine course at the Semmelweis University in Hungary}, url = {https://m2.mtmt.hu/api/publication/34827426}, author = {Kerpel-Fronius, Sándor and Gottwald, M. and Arányi, P. and Renczes, G. and Görbe, Anikó and Papp, Renáta Emese and Ferdinandy, Péter}, doi = {10.3389/fphar.2024.1394987}, journal-iso = {FRONT PHARMACOL}, journal = {FRONTIERS IN PHARMACOLOGY}, volume = {15}, unique-id = {34827426}, abstract = {The pharmaceutical medicine course at the Semmelweis University of Budapest, Hungary, was initiated as part of the Innovative Medicines Initiative (IMI is the main program, IMI-PharmaTrain is one of the IMI projects) Pharmaceutical Medicine Training Programs (16 IMI Call 2008/1/16). The aim was to extend training in the development of pharmaceutical medicine to those EU member states where no such education was present. The final program envisaged the development of a cooperative education supported by universities located in Central and Eastern Europe. It was considered to be the economically and scientifically most viable approach to combine the expertise from these countries to form a united teaching staff and provide education jointly for young professionals of the region. Semmelweis University was selected to manage this coordinated program. In this report, we describe the organization and functioning of this international university-based pharmaceutical medicine education project called the Cooperative European Medicines Development Course (CEMDC) and evaluate its successes and shortcomings. During the pandemic, the educational course was interrupted. The follow-on program is reorganized as a postgraduate MSc course named “Semmelweis Pharma MBA” and will be started in 2025. It will continue the established PharmaTrain educational tradition. However, it will deal in more detail with the transition from basic pharmacological to industrial research, as well as biopharmaceutical formulation and manufacturing and marketing aspects of medicines development.}, year = {2024}, eissn = {1663-9812}, orcid-numbers = {Kerpel-Fronius, Sándor/0000-0002-3245-7414; Görbe, Anikó/0000-0003-4908-1094; Ferdinandy, Péter/0000-0002-6424-6806} } @article{MTMT:34799327, title = {NASH triggers cardiometabolic HFpEF in aging mice}, url = {https://m2.mtmt.hu/api/publication/34799327}, author = {Kucsera, Dániel and Ruppert, Mihály and Sayour, Viktor Nabil and Tóth, Viktória and Kovács, Tamás and Hegedűs, Zsombor and Onódi, Zsófia and Fábián, Alexandra and Kovács, Attila and Radovits, Tamás and Merkely, Béla Péter and Pacher, Pál and Ferdinandy, Péter and Varga, Zoltán}, doi = {10.1007/s11357-024-01153-9}, journal-iso = {GEROSCIENCE}, journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)}, volume = {In press}, unique-id = {34799327}, issn = {2509-2715}, abstract = {Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges. Therefore, the potential link between the two disease is important to study. We aimed to evaluate whether NASH is an independent factor of cardiac dysfunction and to investigate the age dependent effects of NASH on cardiac function. C57Bl/6 J middle aged (10 months old) and aged mice (24 months old) were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon termination, organ samples were isolated for histological and molecular analysis. CDAA diet led to the development of NASH in both age groups, without inducing weight gain, allowing to study the direct effect of NASH on cardiac function. Mice with NASH developed hepatomegaly, fibrosis, and inflammation. Aged animals had increased heart weight. Conventional echocardiography revealed normal systolic function in all cohorts, while increased left ventricular volumes in aged mice. Two-dimensional speckle tracking echocardiography showed subtle systolic and diastolic deterioration in aged mice with NASH. Histologic analyses of cardiac samples showed increased cross-sectional area, pronounced fibrosis and Col1a1 gene expression, and elevated intracardiac CD68 + macrophage count with increased Il1b expression. Conventional echocardiography failed to reveal subtle change in myocardial function; however, 2D speckle tracking echocardiography was able to identify diastolic deterioration. NASH had greater impact on aged animals resulting in cardiac hypertrophy, fibrosis, and inflammation.}, year = {2024}, eissn = {2509-2723}, orcid-numbers = {Kucsera, Dániel/0000-0001-9446-847X; Tóth, Viktória/0000-0002-0426-2425; Kovács, Tamás/0000-0003-4127-4545; Onódi, Zsófia/0000-0002-3746-8016; Fábián, Alexandra/0000-0002-8449-0638; Kovács, Attila/0000-0003-2320-6434; Merkely, Béla Péter/0000-0001-6514-0723; Pacher, Pál/0000-0001-7036-8108; Ferdinandy, Péter/0000-0002-6424-6806; Varga, Zoltán/0000-0002-2758-0784} } @article{MTMT:34753997, title = {Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review}, url = {https://m2.mtmt.hu/api/publication/34753997}, author = {Papapetropoulos, Andreas and Topouzis, Stavros and Alexander, Steve P. H. and Cortese‐Krott, Miriam and Kendall, Dave A. and Martemyanov, Kirill A. and Mauro, Claudio and Nagercoil, Nithyanandan and Panettieri, Reynold A. and Patel, Hemal H. and Schulz, Rainer and Stefanska, Barbara and Stephens, Gary J. and Teixeira, Mauro M. and Vergnolle, Nathalie and Wang, Xin and Ferdinandy, Péter}, doi = {10.1111/bph.16337}, journal-iso = {BR J PHARMACOL}, journal = {BRITISH JOURNAL OF PHARMACOLOGY}, volume = {181}, unique-id = {34753997}, issn = {0007-1188}, abstract = {In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as “first‐in‐class” (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development. We succinctly describe the mechanism of action of most of these FIC drugs and discuss the therapeutic areas covered, as well as the chemical category to which these drugs belong. The 2023 novel drug list also demonstrates an unabated emphasis on polypeptides (recombinant proteins and antibodies), Advanced Therapy Medicinal Products (gene and cell therapies) and RNA therapeutics, including the first‐ever approval of a CRISPR‐Cas9‐based gene‐editing cell therapy.}, year = {2024}, eissn = {1476-5381}, pages = {1553-1575}, orcid-numbers = {Papapetropoulos, Andreas/0000-0002-4253-5930; Topouzis, Stavros/0000-0001-5443-5016; Alexander, Steve P. H./0000-0003-4417-497X; Cortese‐Krott, Miriam/0000-0002-0593-1192; Kendall, Dave A./0000-0001-8740-6764; Mauro, Claudio/0000-0002-3736-0099; Panettieri, Reynold A./0000-0003-0834-4636; Patel, Hemal H./0000-0001-6722-9625; Stephens, Gary J./0000-0002-8966-4238; Teixeira, Mauro M./0000-0002-6944-3008; Vergnolle, Nathalie/0000-0003-1825-6015; Wang, Xin/0000-0001-7678-0785; Ferdinandy, Péter/0000-0002-6424-6806} } @article{MTMT:34724783, title = {Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence}, url = {https://m2.mtmt.hu/api/publication/34724783}, author = {Sayour, Viktor Nabil and Paál, Ágnes and Ameri, Pietro and Meijers, Wouter C and Minotti, Giorgio and Andreadou, Ioanna and Lombardo, Antonella and Camilli, Massimiliano and Drexel, Heinz and Grove, Erik Lerkevang and Dan, Gheorghe Andrei and Ivanescu, Andreea and Semb, Anne Grete and Savarese, Gianluigi and Dobrev, Dobromir and Crea, Filippo and Kaski, Juan-Carlos and de Boer, Rudolf A and Ferdinandy, Péter and Varga, Zoltán}, doi = {10.1093/eurheartj/ehae105}, journal-iso = {EUR HEART J}, journal = {EUROPEAN HEART JOURNAL}, volume = {45}, unique-id = {34724783}, issn = {0195-668X}, abstract = {Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.}, year = {2024}, eissn = {1522-9645}, pages = {1224-1240}, orcid-numbers = {Paál, Ágnes/0000-0003-2292-3714; Minotti, Giorgio/0000-0002-5678-6175; Camilli, Massimiliano/0000-0002-2940-5349; Dobrev, Dobromir/0000-0002-4612-117X; Kaski, Juan-Carlos/0000-0001-8068-0189; de Boer, Rudolf A/0000-0002-4775-9140; Ferdinandy, Péter/0000-0002-6424-6806; Varga, Zoltán/0000-0002-2758-0784} } @article{MTMT:34717730, title = {Cellular Alterations in Immune Checkpoint Inhibitor Therapy-Related Cardiac Dysfunction}, url = {https://m2.mtmt.hu/api/publication/34717730}, author = {Michel, Lars and Ferdinandy, Péter and Rassaf, Tienush}, doi = {10.1007/s11897-024-00652-2}, journal-iso = {CURR HEART FAIL REP}, journal = {CURRENT HEART FAILURE REPORTS}, unique-id = {34717730}, issn = {1546-9530}, year = {2024}, eissn = {1546-9549}, orcid-numbers = {Ferdinandy, Péter/0000-0002-6424-6806} } @article{MTMT:34676111, title = {New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023}, url = {https://m2.mtmt.hu/api/publication/34676111}, author = {Tamargo, Juan and Agewall, Stefan and Borghi, Claudio and Ceconi, Claudio and Cerbai, Elisabetta and Dan, Gheorghe A and Ferdinandy, Péter and Grove, Erik Lerkevang and Rocca, Bianca and Magavern, Emma and Sulzgruber, Patrick and Semb, Anne Grete and Sossalla, Samuel and Niessner, Alexander and Kaski, Juan Carlos and Dobrev, Dobromir}, doi = {10.1093/ehjcvp/pvae013}, journal-iso = {EUR HEART J-CARD PHA}, journal = {EUROPEAN HEART JOURNAL - CARDIOVASCULAR PHARMACOTHERAPY}, unique-id = {34676111}, issn = {2055-6837}, abstract = {Although cardiovascular diseases are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic cardiovascular disease and heart failure. The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolemia, type 2 diabetes, obesity and heart failure, the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of cardiovascular diseases.}, year = {2024}, eissn = {2055-6845}, orcid-numbers = {Tamargo, Juan/0000-0002-7979-7758; Borghi, Claudio/0000-0001-8039-8781; Cerbai, Elisabetta/0000-0001-7839-1361; Ferdinandy, Péter/0000-0002-6424-6806; Sulzgruber, Patrick/0000-0001-5146-0099; Niessner, Alexander/0000-0001-8888-0935; Dobrev, Dobromir/0000-0002-4612-117X} } @article{MTMT:34538456, title = {Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure}, url = {https://m2.mtmt.hu/api/publication/34538456}, author = {Gergely, Tamás G and Drobni, Zsófia and Kallikourdis, Marinos and Zhu, Han and Meijers, Wouter C. and Neilan, Tomas G. and Rassaf, Tienush and Ferdinandy, Péter and Varga, Zoltán}, doi = {10.1038/s41569-023-00986-9}, journal-iso = {NAT REV CARDIOL}, journal = {NATURE REVIEWS CARDIOLOGY}, unique-id = {34538456}, issn = {1759-5002}, year = {2024}, eissn = {1759-5010}, orcid-numbers = {Drobni, Zsófia/0000-0002-1355-5318; Zhu, Han/0000-0002-2751-7814; Neilan, Tomas G./0000-0003-4356-8176; Ferdinandy, Péter/0000-0002-6424-6806; Varga, Zoltán/0000-0002-2758-0784} } @article{MTMT:34474992, title = {YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy}, url = {https://m2.mtmt.hu/api/publication/34474992}, author = {Heger, Jacqueline and Partsch, Stefan and Harjung, Claudia and Varga, Zoltán and Baranyai, Tamás and Weiß, Johannes and Kremer, Lea and Locquet, Fabian and Leszek, Przemyslaw and Ágg, Bence and Benczik, Bettina and Ferdinandy, Péter and Schulz, Rainer and Euler, Gerhild}, doi = {10.3390/ijms25010401}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34474992}, issn = {1661-6596}, abstract = {Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy (n = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to YB-1, whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of YB-1 in CMs, caused by infection with an adenovirus encoding YB-1 (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; n = 10–16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. YB-1 overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 (RGS2) under PE stimulation (n = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches.}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Varga, Zoltán/0000-0002-2758-0784; Baranyai, Tamás/0000-0002-9378-8938; Ágg, Bence/0000-0002-6492-0426; Benczik, Bettina/0000-0003-0379-2181; Ferdinandy, Péter/0000-0002-6424-6806; Schulz, Rainer/0000-0003-3017-0476; Euler, Gerhild/0000-0001-9094-773X} } @article{MTMT:34425939, title = {The Semmelweis Study: a longitudinal occupational cohort study within the framework of the Semmelweis Caring University Model Program for supporting healthy aging}, url = {https://m2.mtmt.hu/api/publication/34425939}, author = {Ungvári, Zoltán István and Tabák, Ádám and Ádány, Róza and Purebl, György and Kaposvári, Csilla and Fazekas-Pongor, Vince and Csípő, Tamás and Szarvas, Zsófia and Horváth, Krisztián and Mukli, Péter and Balog, Piroska and Bódizs, Róbert and Ujma, Przemyslaw Péter and Stauder, Adrienne and Belsky, Daniel W. and Kovács, Illés and Yabluchanskiy, Andriy and Maier, Andrea B. and Moizs, Mariann and Östlin, Piroska and Yon, Yongjie and Varga, Péter and Vokó, Zoltán and Papp, Magor Csongor and Takács, István and Vásárhelyi, Barna and Torzsa, Péter and Ferdinandy, Péter and Csiszar, Anna and Benyó, Zoltán and Szabó, Attila and Bednárikné Dörnyei, Gabriella and Kivimäki, Mika and Kellermayer, Miklós and Merkely, Béla Péter}, doi = {10.1007/s11357-023-01018-7}, journal-iso = {GEROSCIENCE}, journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)}, volume = {46}, unique-id = {34425939}, issn = {2509-2715}, abstract = {The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions.}, year = {2024}, eissn = {2509-2723}, pages = {191-218}, orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Tabák, Ádám/0000-0002-6234-3936; Purebl, György/0000-0002-9750-2001; Fazekas-Pongor, Vince/0000-0002-6405-4003; Szarvas, Zsófia/0000-0002-0022-5053; Mukli, Péter/0000-0003-4355-8103; Balog, Piroska/0000-0001-5025-8649; Bódizs, Róbert/0000-0001-5341-060X; Ujma, Przemyslaw Péter/0000-0002-7981-3009; Stauder, Adrienne/0000-0002-0358-3657; Kovács, Illés/0000-0001-5763-0482; Vokó, Zoltán/0000-0002-1004-1848; Takács, István/0000-0002-7810-4833; Vásárhelyi, Barna/0000-0003-0055-7346; Torzsa, Péter/0000-0002-8148-4961; Ferdinandy, Péter/0000-0002-6424-6806; Benyó, Zoltán/0000-0001-6015-0359; Szabó, Attila/0000-0001-7321-9861; Bednárikné Dörnyei, Gabriella/0000-0001-7007-6252; Kellermayer, Miklós/0000-0002-5553-6553; Merkely, Béla Péter/0000-0001-6514-0723} } @article{MTMT:34368153, title = {An Observational Study on the Pharmacokinetics of Oseltamivir in Lactating Influenza Patients}, url = {https://m2.mtmt.hu/api/publication/34368153}, author = {Fodor, Eszter and Nagy, Regina Norma and Nógrádi, András and Toovey, Stephen and Kamal, Mohamed A. and Vadász, Péter and Bencsik, Péter and Görbe, Anikó and Ferdinandy, Péter}, doi = {10.1002/cpt.3107}, journal-iso = {CLIN PHARMACOL THER}, journal = {CLINICAL PHARMACOLOGY & THERAPEUTICS}, volume = {115}, unique-id = {34368153}, issn = {0009-9236}, abstract = {Influenza infection may lead to serious complications in the postpartum period, therefore, oseltamivir treatment in these patients and their breastfed infants is of great importance. However, the pharmacokinetics of oseltamivir in postpartum lactating women with acute influenza infection, and the consequent infant exposure to oseltamivir are still unknown, and these data would help in assessing risk and the need for dose adjustment in breastfed infants.}, year = {2024}, eissn = {1532-6535}, pages = {318-323}, orcid-numbers = {Nagy, Regina Norma/0000-0002-3253-5398; Bencsik, Péter/0000-0003-1936-6232; Görbe, Anikó/0000-0003-4908-1094; Ferdinandy, Péter/0000-0002-6424-6806} }