https://hdl.handle.net/20.500.14178/906 2026-08-19T19:54:56Z 2026-08-19T19:54:56Z Houngbedji, Priam-Amedeo Bachtíková, Andrea Boháčová, Jarmila Tabarestani, Parinaz Janďourek, Ondřej Konečná, Klára Ősterreicher, Jan Paterová, Pavla Novák, Martin Bárta, Pavel Záhorszká, Monika Korduláková, Jana Mori, Matteo Meneghetti, Fiorella Zitko, Jan https://hdl.handle.net/20.500.14178/3889 2026-08-05T01:00:16Z 2026-01-01T00:00:00Z

Pyrazinamide-derived 1,2,3-triazoles: Antimicrobial evaluation, selective antimycobacterial activity and mechanism of action insights Houngbedji, Priam-Amedeo; Bachtíková, Andrea; Boháčová, Jarmila; Tabarestani, Parinaz; Janďourek, Ondřej; Konečná, Klára; Ősterreicher, Jan; Paterová, Pavla; Novák, Martin; Bárta, Pavel; Záhorszká, Monika; Korduláková, Jana; Mori, Matteo; Meneghetti, Fiorella; Zitko, Jan A series of pyrazinamide-derived 1,2,3-triazoles featuring systematic chlorination of the pyrazine ring and diverse aryl substituents was synthesized and evaluated for antimycobacterial activity. Biological activity screening revealed broad-spectrum antimycobacterial activity and good selectivity toward mycobacteria over other pathogens, with 11 of the prepared compounds showing activity against Mycobacterium tuberculosis (Mtb) H37Ra and/or Mtb H37Rv (MIC <= 62.5 mu g/mL). Structure-activity relationship analysis showed that 5-Cl substitution on the pyrazine ring was associated with improved antimycobacterial activity, with the best MIC values observed for compound 7 against Mtb H37Ra (MIC =1.98 mu g/mL) and compound 37 against Mtb H37Rv (MIC =1.56 mu g/mL). The tested compounds retained activity against drug-resistant Mtb isolates and partially against naturally resistant Mycobacterium abscessus, while showing low in vitro cytotoxicity in the HepG2 cell line and favorable selectivity indices. During advanced cytotoxicity testing, both compounds 7 and 37 displayed substantially lower hemolytic activity than bedaquiline, indicating a favorable erythrocyte safety profile within the tested concentration ranges. In vivo toxicity testing on Galleria mellonella showed low acute toxicity for both compounds. Mechanistic studies on compounds 7, 27, 31, and 37 revealed reduced biosynthesis of fatty acids and derived lipids, a phenotype consistent with interference with the Fatty Acid Synthase I (FAS I) system.

2026-01-01T00:00:00Z Brkić, Jovana Reissigová, Jindra Okuyan, Betül Ortner Hadžiabdić, Maja Marinković, Valentina Somers, Annemie Onder, Graziano Šesto, Sofija Altiparmak, Öznur Kummer, Ingrid Držaić, Margita Fialová, Daniela https://hdl.handle.net/20.500.14178/3473 2026-01-30T02:00:24Z 2025-01-01T00:00:00Z

Assessing potentially inappropriate medication use among older adults in Central and Eastern Europe Brkić, Jovana; Reissigová, Jindra; Okuyan, Betül; Ortner Hadžiabdić, Maja; Marinković, Valentina; Somers, Annemie; Onder, Graziano; Šesto, Sofija; Altiparmak, Öznur; Kummer, Ingrid; Držaić, Margita; Fialová, Daniela Objective The aim of this study was to examine the prevalence of potentially inappropriate medication (PIM) use and its associated risk factors in community-dwelling older adults from five Central and Eastern European (CEE) countries. Materials and methods This secondary analysis of a cross-sectional survey, which was part of the Horizon 2020 EuroAgeism ESR7 project, was conducted between February 2019 and March 2020 in Bulgaria, Croatia, Czechia, Estonia, and Serbia. We enrolled older adults aged >= 65 years who visited community pharmacies to acquire medications. The prevalence of PIM use was determined by applying all 282 criteria from the EU(7)-PIM list. Risk and protective factors for PIM use were evaluated using multiple logistic regression. R software version 4.3.2 was used in statistical analysis. Results Most of the 2,155 participants were women (63.3%) and aged 65-74 years (64.8%). The overall PIM prevalence was 56.0% (95% confidence interval 53.8%-58.1%), ranging from 29.5% in Czechia to 70.0% in Croatia. The most commonly used PIMs were benzodiazepines (16.7% of all PIMs), followed by nonsteroidal anti-inflammatory drugs (14.3%), and proton pump inhibitors taken for more than 8 weeks (14.1%). Multiple logistic regression revealed that residence, increasing comorbidity burden, and polypharmacy were significant risk factors associated with PIM use in older adults. Conclusions Our findings demonstrate a high prevalence of PIM use among older patients from CEE countries and considerable cross-country differences, underscoring the need to improve medication prescribing for older adults to improve healthcare quality and patient outcomes.

2025-01-01T00:00:00Z Držaić, Margita Bužančić, Iva Kummer, Ingrid Bošković, Andrea Glavaš, Dragan Ortner Hadžiabdić, Maja Brkić, Jovana Fialová, Daniela https://hdl.handle.net/20.500.14178/3472 2026-01-28T02:00:18Z 2025-01-01T00:00:00Z

Anticholinergic and Sedative Medication Burden in Croatian Older Adults: EuroAgeism Cohort Findings Držaić, Margita; Bužančić, Iva; Kummer, Ingrid; Bošković, Andrea; Glavaš, Dragan; Ortner Hadžiabdić, Maja; Brkić, Jovana; Fialová, Daniela Use of anticholinergic and sedative medications is potentially inappropriate in older adults due to associated adverse effects, including impaired cognitive and physical function. This study evaluated anticholinergic and sedative burden in Croatian community-dwelling older adults using the Drug Burden Index (DBI) and examined its association with self-reported health and healthcare utilization over 12 months. This observational, cross-sectional study, part of the EuroAgeism H2020 ESR 7 project, included conveniently sampled adults >= 65 years from community pharmacies in three Croatian regions. Data were collected using a standardized research questionnaire. DBI was used to quantify exposure to anticholinergic and sedative medications. Multivariate regression analyses examined associations between DBI and health outcomes, using logistic regression for binary outcomes and linear regression for self-reported health. Among 388 participants (63.7% female, median age 73), most had multimorbidity (median five diagnoses) and polypharmacy (63.9%), while 57% used at least one DBI medication - most commonly diazepam (15.5%) and tramadol (14.7%). High DBI (>= 1) independently predicted more emergency department (ED) visits (OR = 2.45) and worse self-rated health (B = -0.26), but not hospitalization. High DBI in older adults was associated with more ED visits and poorer self-rated health, highlighting the need for targeted interventions to reduce anticholinergic and sedative use in this vulnerable population.

2025-01-01T00:00:00Z Ali, Mohammed Adler, Mariia Libra, Antonín Vokřál, Ivan Karahoda, Rona Cífková, Eva Lísa, Miroslav Tomek, Jakub Novotná, Magdaléna Štaud, František Červený, Lukáš https://hdl.handle.net/20.500.14178/3455 2026-01-16T02:00:16Z 2025-01-01T00:00:00Z

Dynamic shifts in trophoblast nucleos(t)ide metabolism, transport, and adenosine signaling during gestation and preterm birth Ali, Mohammed; Adler, Mariia; Libra, Antonín; Vokřál, Ivan; Karahoda, Rona; Cífková, Eva; Lísa, Miroslav; Tomek, Jakub; Novotná, Magdaléna; Štaud, František; Červený, Lukáš Nucleos(t)ides are essential for DNA/RNA synthesis, energy metabolism, and signaling, yet their roles in placental development remain poorly understood. The placenta undergoes dynamic metabolic adaptations throughout gestation to support fetal growth. This study investigates gene expression shifts in nucleos(t)ide metabolism, transport, and adenosine signaling during placental development and in the pathological condition of spontaneous preterm birth (PTB). We analyzed gene expression in first-trimester (n = 10) and term (n = 10), and PTB (n = 10) human placentas, and in cytotrophoblast and syncytiotrophoblast stage in primary human trophoblasts (n = 3) and BeWo (n = 5) cells. For developmental context, rat placentas were examined at gestation days (GD) GD12, GD15, and GD20 (n = 5 per group) that correspond to early second trimester in the human placenta. We found that genes involved in nucleos(t)ide metabolism and adenosine signaling were dominantly upregulated from early gestation to term in the human placenta. PTB placentas revealed further elevation compared to the term placenta. Differentiation from cytotrophoblast to syncytiotrophoblast was accompanied by only minor changes. Pearson's correlation analysis revealed strong gene-metabolite and gene-gene associations, highlighting an integrated metabolic network regulating placental function. Gene expression also differed among the tested GDs in the rat placenta. These findings demonstrate dynamic changes of nucleos(t)ide metabolism during healthy placental development and enhanced expression in PTB placentas, suggesting increasing needs for nucleos(t)ides during placental growth and metabolic shifts in the PTB placenta. Our data also indicate that nucleos(t)ide metabolism is preserved in both proliferative and differentiated states.

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