TY - CONF AU - Fésüs, Adina AU - Matuz, M AU - Hambalek, H AU - Ruzsa, R AU - Tánczos, B AU - Bácskay, I AU - Illés, Á AU - Benkő, R TI - 4CPS-036 Evaluation of the diagnosis and antibiotic prescription pattern in patients hospitalised with urinary tract infections (UTIs) T2 - Section 4: Clinical pharmacy services PB - British Medical Journal Publishing Group PY - 2024 SP - A68.2 EP - A68 DO - 10.1136/ejhpharm-2024-eahp.140 UR - https://m2.mtmt.hu/api/publication/34756237 ID - 34756237 LA - English DB - MTMT ER - TY - CONF AU - Fésüs, Adina AU - Baluku, P AU - Sipos, É AU - Somodi, S AU - Vaskó, A AU - Lekli, I AU - Berczi-Kun, E AU - Bácskay, I TI - 4CPS-035 Impact of antibiotic stewardship programme (ASP) on antibiotic use and clinical outcomes in patients hospitalised with community-acquired pneumonia (CAP): retrospective observational before-after study T2 - Section 4: Clinical pharmacy services PB - British Medical Journal Publishing Group PY - 2024 SP - A68.1 EP - A68 DO - 10.1136/ejhpharm-2024-eahp.139 UR - https://m2.mtmt.hu/api/publication/34756232 ID - 34756232 LA - English DB - MTMT ER - TY - JOUR AU - Ababneh, Haneen AU - Balogh, Enikő AU - Csiki, Dávid Máté AU - Lente, Gréta AU - Fenyvesi, Ferenc AU - Tóth, Andrea AU - Jeney, Viktória TI - High glucose promotes osteogenic differentiation of human lens epithelial cells through hypoxia-inducible factor (HIF) activation JF - JOURNAL OF CELLULAR PHYSIOLOGY J2 - J CELL PHYSIOL PY - 2024 PG - 12 SN - 0021-9541 DO - 10.1002/jcp.31211 UR - https://m2.mtmt.hu/api/publication/34618976 ID - 34618976 AB - Cataract, a leading cause of blindness, is characterised by lens opacification. Type 2 diabetes is associated with a two- to fivefold higher prevalence of cataracts. The risk of cataract formation increases with the duration of diabetes and the severity of hyperglycaemia. Hydroxyapatite deposition is present in cataractous lenses that could be the consequence of osteogenic differentiation and calcification of lens epithelial cells (LECs). We hypothesised that hyperglycaemia might promote the osteogenic differentiation of human LECs (HuLECs). Osteogenic medium (OM) containing excess phosphate and calcium with normal (1 g/L) or high (4.5 g/L) glucose was used to induce HuLEC calcification. High glucose accelerated and intensified OM-induced calcification of HuLECs, which was accompanied by hyperglycaemia-induced upregulation of the osteogenic markers Runx2, Sox9, alkaline phosphatase and osteocalcin, as well as nuclear translocation of Runx2. High glucose-induced calcification was abolished in Runx2-deficient HuLECs. Additionally, high glucose stabilised the regulatory alpha subunits of hypoxia-inducible factor 1 (HIF-1), triggered nuclear translocation of HIF-1 alpha and increased the expression of HIF-1 target genes. Gene silencing of HIF-1 alpha or HIF-2 alpha attenuated hyperglycaemia-induced calcification of HuLECs, while hypoxia mimetics (desferrioxamine, CoCl2) enhanced calcification of HuLECs under normal glucose conditions. Overall, this study suggests that high glucose promotes HuLEC calcification via Runx2 and the activation of the HIF-1 signalling pathway. These findings may provide new insights into the pathogenesis of diabetic cataracts, shedding light on potential factors for intervention to treat this sight-threatening condition. LA - English DB - MTMT ER - TY - JOUR AU - Skopkó, Boglárka Emese AU - Homoki, Judit Rita AU - Fazekas, Mónika Éva AU - Paholcsek, Melinda AU - Fauszt, Péter AU - Dávid, Péter AU - Stündl, László AU - Molnár, Piroska Bíróné AU - Forgács, Ildikó Noémi AU - Váradi, Judit AU - Bágyi, Kinga, Ágnes AU - Gálné Remenyik, Judit TI - Changes in the Composition of Unstimulated and Stimulated Saliva Due to Chewing Sour Cherry Gum and a Toothbrush Change JF - CELLS J2 - CELLS-BASEL VL - 13 PY - 2024 IS - 3 SN - 2073-4409 DO - 10.3390/cells13030251 UR - https://m2.mtmt.hu/api/publication/34546012 ID - 34546012 AB - Background: Our previous studies demonstrated that sour cherry anthocyanins (AC) reduce the salivary count of Streptococcus mutans and inhibit salivary amylase activity within 30 minutes after chewing AC gum. AC gum and changing toothbrushes after scaling reduced the Gram-negative species in the unstimulated salivary microbiota. The present study examined the effect of AC gums on salivary factors, including changes in microbiome. Methods: The study was conducted over three weeks with two groups; young adults (18–30) and adults (30–45). Ten participants changed their toothbrushes, while the other 10 participants did not change after the control period. After scaling, all participants received three doses of AC gum daily. The salivary mRNA and protein levels of cytokines, mucins, melatonin, and the microbiota of unstimulated and stimulated saliva were determined by polymerase chain reaction, enzyme-linked immunosorbent assay, and 16S rRNA gene sequencing. Results: Significantly higher levels of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), mucin5B (MUC5B), mucin7 (MUC7), and melatonin were detected in stimulated saliva. Correlation analysis of these factors with the microbiota showed positive correlations with the genera Lachnospiraceae, Eikenella, Saccharibacteria_(TM7), Streptococcus, Prevotella, and Haemophilus. Conclusions: AC chewing gum has a beneficial effect on the composition of the oral microbiome, and toothbrush replacement leads to changes in the levels of salivary pro-inflammatory cytokines. LA - English DB - MTMT ER - TY - JOUR AU - Feró, Orsolya AU - Varga, Dóra AU - Nagy, Éva AU - Karányi, Zsolt AU - Sipos, Éva AU - Engelhardt, József AU - Török, Nóra AU - Balogh, István AU - Vető, Borbála AU - Likó, István AU - Fóthi, Ábel AU - Szabó, Zoltán AU - Halmos, Gábor AU - Vécsei, László AU - Arányi, Tamás AU - Székvölgyi, Lóránt TI - DNA methylome, R-loop and clinical exome profiling of patients with sporadic amyotrophic lateral sclerosis JF - SCIENTIFIC DATA J2 - SCI DATA VL - 11 PY - 2024 IS - 1 PG - 12 SN - 2052-4463 DO - 10.1038/s41597-024-02985-y UR - https://m2.mtmt.hu/api/publication/34534306 ID - 34534306 N1 - MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Molecular and Nanopharmaceutics, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary Doctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Molecular Biology, Semmelweis University, Budapest, Hungary Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Export Date: 13 February 2024; Cited By: 0; Correspondence Address: L. Székvölgyi; MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Molecular and Nanopharmaceutics, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary; email: lorantsz@med.unideb.hu; T. Arányi; Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; email: aranyi.tamas@ttk.hu AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the death of motor neurons, the aetiology of which is essentially unknown. Here, we present an integrative epigenomic study in blood samples from seven clinically characterised sporadic ALS patients to elucidate molecular factors associated with the disease. We used clinical exome sequencing (CES) to study DNA variants, DNA-RNA hybrid immunoprecipitation sequencing (DRIP-seq) to assess R-loop distribution, and reduced representation bisulfite sequencing (RRBS) to examine DNA methylation changes. The above datasets were combined to create a comprehensive repository of genetic and epigenetic changes associated with the ALS cases studied. This repository is well-suited to unveil new correlations within individual patients and across the entire patient cohort. The molecular attributes described here are expected to guide further mechanistic studies on ALS, shedding light on the underlying genetic causes and facilitating the development of new epigenetic therapies to combat this life-threatening disease. LA - English DB - MTMT ER - TY - JOUR AU - Hermenean, Anca AU - Dossi, Eleftheria AU - Hamilton, Alex AU - Trotta, Maria Consiglia AU - Russo, Marina AU - Lepre, Caterina Claudia AU - Sajtos, Csilla AU - Rusznyák, Ágnes AU - Váradi, Judit AU - Bácskay, Ildikó AU - Budai, István AU - D’Amico, Michele AU - Fenyvesi, Ferenc TI - Chrysin Directing an Enhanced Solubility through the Formation of a Supramolecular Cyclodextrin–Calixarene Drug Delivery System: A Potential Strategy in Antifibrotic Diabetes Therapeutics JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 17 PY - 2024 IS - 1 SP - 1 EP - 20 PG - 20 SN - 1424-8247 DO - 10.3390/ph17010107 UR - https://m2.mtmt.hu/api/publication/34500966 ID - 34500966 AB - Calixarene 0118 (OTX008) and chrysin (CHR) are promising molecules for the treatment of fibrosis and diabetes complications but require an effective delivery system to overcome their low solubility and bioavailability. Sulfobutylated β-cyclodextrin (SBECD) was evaluated for its ability to increase the solubility of CHR by forming a ternary complex with OTX008. The resulting increase in solubility and the mechanisms of complex formation were identified through phase-solubility studies, while dynamic light-scattering assessed the molecular associations within the CHR-OTX008-SBECD system. Nuclear magnetic resonance, differential scanning calorimetry, and computational studies elucidated the interactions at the molecular level, and cellular assays confirmed the system’s biocompatibility. Combining SBECD with OTX008 enhances CHR solubility more than using SBECD alone by forming water-soluble molecular associates in a ternary complex. This aids in the solubilization and delivery of CHR and OTX008. Structural investigations revealed non-covalent interactions essential to complex formation, which showed no cytotoxicity in hyperglycemic in vitro conditions. A new ternary complex has been formulated to deliver promising antifibrotic agents for diabetic complications, featuring OTX008 as a key structural and pharmacological component. LA - English DB - MTMT ER - TY - JOUR AU - Bácskay, Ildikó AU - Hosszú, Zsolt AU - Budai, István AU - Ujhelyi, Zoltán AU - Siposné Fehér, Pálma AU - Kósa, Dóra AU - Haimhoffer, Ádám AU - Pető, Ágota TI - Formulation and Evaluation of Transdermal Patches Containing BGP-15 JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 1 PG - 18 SN - 1999-4923 DO - 10.3390/pharmaceutics16010036 UR - https://m2.mtmt.hu/api/publication/34452575 ID - 34452575 AB - BGP-15 is an active ingredient with many advantages, e.g., beneficial cardiovascular and anti-inflammatory effects. The transdermal administration of BGP-15 has great potential, which has not been investigated yet, despite the fact that it is a non-invasive and safe form of treatment. The aim of our study was to formulate transdermal patches containing BGP-15 and optimize the production with the Box–Behnken design of experiment. The most optimal formulation was further combined with penetration enhancers to improve bioavailability of the active ingredient, and the in vitro drug release and in vitro permeation of BGP-15 from the patches were investigated. FTIR spectra of BGP-15, the formulations and the components were also studied. The most optimal formulation based on the tested parameters was dried for 24 h, with 67% polyvinyl alcohol (PVA) content and low ethanol content. The selected penetration enhancer excipients were not cytotoxic on HaCaT cells. The FTIR measurements and SEM photography proved the compatibility of the active substance and the vehicle; BGP-15 was present in the polymer matrix in dissolved form. The bioavailability of BGP-15 was most significantly enhanced by the combination of Transcutol and Labrasol. The in vitro permeation study confirmed that the formulated patches successfully enabled the transdermal administration of BGP-15. LA - English DB - MTMT ER - TY - CONF AU - Fésüs, Adina AU - Anita, Kónya-Ábrahám AU - Éva, Sipos AU - Kitti, Szőke AU - István, Bak AU - Attila, Kiss-Szikszai AU - István, Lekli TI - Evaluation of the antioxidant effect of kd15 and kd36 newly synthetized molecules T2 - FAMÉ 2023 PY - 2023 SP - 223 UR - https://m2.mtmt.hu/api/publication/34425898 ID - 34425898 LA - English DB - MTMT ER - TY - JOUR AU - Fésüs, Adina AU - Matuz, Mária AU - Papfalvi, Erika Piroska AU - Hambalek, Helga AU - Ruzsa, Roxána AU - Tánczos, Bence AU - Bácskay, Ildikó AU - Lekli, István AU - Illés, Árpád AU - Benkő, Ria TI - Evaluation of the Diagnosis and Antibiotic Prescription Pattern in Patients Hospitalized with Urinary Tract Infections: Single-Center Study from a University-Affiliated Hospital JF - ANTIBIOTICS J2 - ANTIBIOTICS-BASEL VL - 12 PY - 2023 IS - 12 PG - 19 SN - 2079-6382 DO - 10.3390/antibiotics12121689 UR - https://m2.mtmt.hu/api/publication/34413320 ID - 34413320 AB - UTIs (urinary tract infections) are common bacterial infections with a non-negligible hospitalization rate. The diagnosis of UTIs remains a challenge for prescribers and a common source of misdiagnosis. This retrospective observational study aimed to evaluate whether recorded diagnosis by clinicians and empirical antibiotic therapy met the EAU (European Association of Urology) guideline in patients hospitalized with UTI. The study was conducted at an internal medicine unit of a tertiary care medical center in Hungary. The diagnosis was assessed based on clinical presentation, physical examination, and laboratory (including microbiological) results, considering all the potential risk factors. Diagnosis was considered misdiagnosis when not confirmed by clinical presentation or clinical signs and symptoms. Evaluation of empirical antibiotic therapy was performed only for confirmed UTIs. Empirical treatment was considered guideline-adherent when complying with the relevant recommendations. Out of 185 patients, 41.6% failed to meet EAU-based UTI diagnosis criteria, of which 27.6% were misdiagnosed and 14.1% were ABU (asymptomatic bacteriuria). The diagnosis of urosepsis recorded at admission (9.7%, 18/185) was not confirmed either by clinical or microbiological tests in five (5/18) cases. The initial empirical therapies for UTI showed a relatively low rate (45.4%) of guideline adherence regarding agent selection. The most common guideline-non-adherent therapies were combinations with metronidazole (16.7%). Dosage appropriateness assessments showed a guideline adherence rate of 36.1%, and underdosing due to high body weight was common (9.3%). Overall (agent, route of administration, dose, duration) guideline adherence was found to be substantially low (10.2%). We found a relatively high rate of misdiagnosed UTIs. Written protocols on the ward may be crucial in reducing misdiagnosis and in optimizing antibiotic use. LA - English DB - MTMT ER - TY - JOUR AU - Papp, Boglárka AU - Le Borgne, Marc AU - Perret, Florent AU - Marminon, Christelle AU - Józsa, Liza AU - Pető, Ágota AU - Kósa, Dóra AU - Nagy, Lajos AU - Kéki, Sándor AU - Ujhelyi, Zoltán AU - Pallér, Ádám AU - Budai, István AU - Bácskay, Ildikó AU - Siposné Fehér, Pálma TI - Formulation and Investigation of CK2 Inhibitor-Loaded Alginate Microbeads with Different Excipients JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 12 SP - 2701 SN - 1999-4923 DO - 10.3390/pharmaceutics15122701 UR - https://m2.mtmt.hu/api/publication/34406873 ID - 34406873 AB - The aim of this study was to formulate and characterize CK2 inhibitor-loaded alginate microbeads via the polymerization method. Different excipients were used in the formulation to improve the penetration of an active agent and to stabilize our preparations. Transcutol® HP was added to the drug–sodium alginate mixture and polyvinylpyrrolidone (PVP) was added to the hardening solution, alone and in combination. To characterize the formulations, mean particle size, scanning electron microscopy analysis, encapsulation efficiency, swelling behavior, an enzymatic stability test and an in vitro dissolution study were performed. The cell viability assay and permeability test were also carried out on the Caco-2 cell line. The anti-oxidant and anti-inflammatory effects of the formulations were finally evaluated. The combination of Transcutol® HP and PVP in the formulation of sodium alginate microbeads could improve the stability, in vitro permeability, anti-oxidant and anti-inflammatory effects of the CK2 inhibitor. LA - English DB - MTMT ER -