Donut-shaped [NaP5W30O110]14− polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action

The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH4)14[NaP5W30O110] 31H2O (NaP5W30) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20 mg/kg/day NaP5W30 for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP5W30 (20 mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP5W30 significantly reduced hyperglycemia and glycated haemoglobin A1c (HbA1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP5W30 treatment group compared to the diabetic control group. In contrast, NaP5W30 had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP5W30 effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP5W30 did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP5W30 could be considered a promising antidiabetic drug-candidate that deserves further investigation

Silver-doped bismuth ferrite: enhanced magnetization and theoretical predictions of novel perovskite phases

In this study, we present the hydrothermal synthesis of ultrafine nanopowdersof pure BiFeO₃ (BFO) and Ag-doped Bi1-ₓAgₓFeO₃ (x = 0.01, 0.02). X-raydiffraction confirms that all obtained samples crystallize in the R3c space group. Tofurther investigate structural stability, bond valence calculations (BVCs) wereemployed, predicting several viable perovskite structures and shedding light on thestructural transformations induced by Ag incorporation. Magnetization studiesindicate that while the Néel temperature remains unchanged at T = 630 K across allcompositions, silver doping leads to an increase in both magnetization magnitudeand irreversibility, indicative of weak ferromagnetic behavior. Density functionaltheory (DFT) calculations support this experimental observation, suggesting that Agsubstitution perturbs magnetic interactions between Fe atoms, thereby enhancingmagnetization. Additionally, electronic and magnetic properties were studied for allphases predicted by the BVCs study. DFT predicted half-metallicity in the γ phaseof BFO, which may be of great interest for further study and potential applications.Programme and the Book of Abstracts / 8th Conference of The Serbian Society for Ceramic Materials, 8CSCS-2025, June 14-16, 2025, Belgrade, Serbia

Utilization of Parallel Artiicial Membrane Permeability Assay and Chemometric Modeling for Predicting Blood–Brain Barrier Permeability of Protein Kinase Inhibitors for Brain Anticancer Therapy

This study investigates the passive diffusion of protein kinase inhibitors across the blood- brain barrier (BBB) for brain anticancer therapy and develops a predictive model for their permeability. ..

Multifaceted Biological Properties of Verbascoside/Acteoside: Antimicrobial, Cytotoxic, Anti-Inflammatory, and Immunomodulatory Effects

Verbascoside is a polyphenolic compound that belongs to the phenylethanoid glucosides. It occurs in more than 220 plant species. The species with high content of this compound are used in folk medicine, and in modern phytotherapy, mostly based on its recognized anti-inflammatory and antimicrobial effects. Studies conducted so far confirmed these effects, and also pointed to others (i.e., anti-cancer, neuro-, cardio-, hepato-, and nephro- protective). This review presents data on the chemistry, occurrence, and biosynthesis of verbascoside. Additionally, it focuses on the cytotoxic, antimicrobial, anti-inflammatory, and immunomodulatory effects, as well as the main cellular and molecular mechanisms of its action

Characterization of atorvastatin calcium liquisolid tablets prepared with Neusilin® US2 and Syloid® XDP 3050 as carries

Atorvastain calcium (ATC) is a BCS class II drug known for its low absolute bioavailability (12%), which is due to its poor solubility in gastrointestinal fluids [1]. The technology of liquisolid systems (LSS) has been shown to improve the bioavailability of a number of poorly soluble drugs, primarily due to the increased surface area available for dissolution and the presence of the hydrophilic liquid vehicle, resulting in faster drug release [2]. The aim of this study was to investigate the possibility of using the LS technique to improve the dissolution rate of ATC. Two novel porous excipients with high absorption capacity were selected as carriers to formulate LS tablets with high liquid phase content and suitable mechanical properties as well as acceptable disintegration times and improved dissolution rate

A framework for integrated safety in safety-management systems in healthcare

Purpose – Notwithstanding increased patient safety initiatives, adverse events and their impact on those involved continue. The strategic approaches adopted to manage safety by other high-intensity, high-risk and complex industries, such as aviation, have led to an increase in the systems approach for safety management in healthcare organisations. Professional expertise from members of the European Researchers’ Network for Second Victims (ERNST) highlighted that safety and the second victim phenomenon are interconnected across the healthcare ecosystem, extending beyond individual healthcare organisations. Design/methodology/approach – Evidence from different sources, mainly the literature and practitioner professional expertise, was iteratively aggregated and analysed using theoretical systems-based approaches to conceptualise a framework for integrated safety in safety management systems in health. Findings – A cross-sectional view of the healthcare organisation affected by adverse events was presented as a baseline. The whole system (system levels) approach, representing the healthcare system at the micro-, meso- and macro-level, adapting the model for integrated care, was then adopted. A safety-generating culture was considered to integrate and network across the levels of the healthcare system. The “system” (processes) approach, also considering external factors, was incorporated. This iterative conceptualisation led to a proposed framework for integrated safety. This framework was applied to systematically make recommendations for actions to support safety across the healthcare ecosystem. Originality/value – Aggregation of evidence from the literature, together with expertise from professionals and iterative conceptualisation across models adopting the systems approach, led to a comprehensive framework for integrated safety in safety-management systems

Glucosinolate-Derived Metabolites from Barbarea vulgaris (Brassicaceae): Evaluation of Antimicrobial, Antioxidant, and Anti-Inflammatory Potentials

Glucosinolate-derived metabolites play central roles in plant defense and are increasingly recognized for their pharmacological importance. Barbarea vulgaris produces a structurally diverse set of such compounds, yet their biological activities remain insufficiently explored. In this study, natural metabolites and their synthetic analogues were evaluated for antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties. Antimicrobial activity was assessed against human and plant pathogens by determining minimum inhibitory and minimum microbicidal concentrations, antibiofilm potential was examined using microplate assays, and radical scavenging activity was measured by DPPH and ABTS assays. In addition, the compounds were screened for inhibitory effects on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). Phenolic derivatives, particularly methyl-4-hydroxyphenylethyl dithiocarbamate (2) and 2-(4-hydroxyphenyl)ethyl isothiocyanate (8), exhibited notable in vitro antibacterial activity (MIC 0.312–1.25 mg mL−1 against E. coli ATCC 25922 and S. aureus ATCC 25923) and detectable antibiofilm effects. Racemic barbarin (4) preferentially inhibited LOX, underscoring its potential as an anti-inflammatory scaffold, whereas COX-2 inhibition was weak across all tested compounds. None of the metabolites showed radical scavenging activity, suggesting that their effects rely on enzyme inhibition or microbial interactions rather than nonspecific antioxidant mechanisms. This study provides an integrated evaluation of B. vulgaris metabolites, highlighting their ecological role in plant defense and their potential as scaffolds for novel antimicrobial and anti-inflammatory agents

Precise Control of Structure and Magnetic Properties of BiFeO3: From Synthesis to Prediction of New Modifications

In recent years multiferroics have been an intriguing study field due to their well- known magnetoelectric phenomena that offer a wide range of potentially new applications including spintronics, new data storage media and multiple-state memories [1–5]. Bismuth ferrite (BFO) particles were synthesized via a controlled hydrothermal method, yielding highly pure, small-sized particles. Structural characterization revealed that the as-synthesized (non- annealed) powder crystallizes in the rhombohedral R3c space group with minimal secondary phase content. Upon annealing at 800 °C, a single-phase perovskite structure with high crystallinity was obtained. High-resolution transmission electron microscopy (HRTEM) analysis confirmed the presence of twin stacking faults, which are responsible for enhanced magnetic properties. Electron paramagnetic resonance (EPR) spectroscopy measurements suggested the existence of electrons trapped by vacancies or defects. It has been proposed that the existence of Fe3+−OV defect complex could be generated at elevated temperatures followed by the formation of trivalent Fe ions, which intensely provide local 3d moments. In addition, a structure prediction has been performed and 11 additional BiFeO3 modifications have been proposed, while the magnetic behavior of synthesized material was investigated by SQUID.Advances in Solid State Physics and New Materials - 30 years of the Center for Solid State Physics and New Materials at the Institute of Physics Belgrade, 19 – 23 May 2025, Belgrade, Serbia

Application of statistical approaches in the assessment of rate and extent of absorption and development of a population pharmacokinetic model for clopidogrel and its metabolite clopidogrel carboxylic acid from generic products

Klopidogrel je inhibitor agregacije trombocita, prolek koji se posle p.o. primene brzo resorbuje i intenzivno metaboliše, pre svega presistemski u jetri, pri čemu se veći deo primenjene doze konvertuje do neaktivnog metabolita klopidogrel karboksilne kiseline, a manji deo, oko 15%, do aktivnog metabolita klopidogrel tiola, preko koga klopidogrel ostvaruje svoj efekat. Na tržištu je prisutno više generičkih lekova, za koje je potvrđena biološka ekvivalentnost sa istim referentnim lekom, dok između samih generičkih lekova nije direktno potvrđena. Budući da klopidogrel ima varijabilnu farmakokinetiku, kao i odgovor na terapiju ovim lekom, za kliničku praksu mogu biti značajne informacije o eventualnim razlikama između generičkih lekova u brzini i stepenu resorpcije, zbog kojih kod pacijenata potencijalno može da se poveća rizik od pojave neželjenih reakcija. Cilj prvog dela disertacije bio je poređenje brzine i stepena resorpcije između 19 generičkih lekova klopidogrela, metodama indirektnog i direktnog poređenja, pri čemu su korišćeni rezultati studija biološke ekvivalentnosti koji uključuju primarne i/ili sekundarne podatke za klopidogrel i klopidogrel karboksilnu kiselinu. Cilj drugog dela istraživanja bio je karakterizacija procesa resorpcije i dispozicije klopidogrela, kao i njegove konverzije do klopidogrel karboksilne kiseline, kroz razvoj i validaciju združenog populacionog farmakokinetičkog modela, uz razmatranje faktora varijabilnosti, korišćenjem koncentracija klopidogrela i klopidogrel karboksilne kiseline i drugih dostupnih relevantnih primarnih podataka iz dve studije biološke ekvivalentnosti. Metodom prilagođenog indirektnog poređenja obrađeni su podaci za klopidogrel i klopidogrel karboksilnu kiselinu iz 19 studija biološke ekvivalentnosti i utvrđene su kombinacije generičkih lekova klopidogrela koje se mogu smatrati međusobno biološki ekvivalentnim i potencijalno zamenjivim u kliničkoj praksi (76%), kao i one za koje se zamena ne preporučuje. Direktnim poređenjem farmakokinetičkih parametara iz dve studije biološke ekvivalentnosti korišćenjem Student t-testa, utvrđena je sličnost između generičkih lekova ispitivanih u ovim studijama u pogledu stepena resorpcije kopidogrela i njegove konverzije do klopidogrel karboksilne kiseline, ali ne i u pogledu brzine ovih procesa. Budući da je klinički značaj stepena resorpcije veći u odnosu na brzinu ovog procesa, može se smatrati da između ova dva generička leka nema statistički značajne razlike u biološkoj raspoloživosti. Metodom nelinearnog modelovanja kombinovaniah efekata razvijen je i validiran združeni semi-fiziološki populacioni farmakokinetički model kopidogrela i klopidogrel karboksilne kiseline, koji uključuje linearnu resorpciju sa 2 tranzitna prostora, hepatički prostor za opisivanje presistemskog metabolizma do metabolita, jednoprostorni model za klopidogrel, dvoprostorni model za klopidogrel karboksilnu kiselinu, linearnu eliminaciju ovog metbolita, alomerijsko skaliranje klirensa i volumena distribucije. Razvijeni model daje čvrstu osnovu za potencijalna buduća poboljšanja pri građenju složenijeg modela. Sprovedeno istraživanje koristi savremene metode analize sekundarnih i/ili primarnih podataka dostupnih za generičke lekove klopidogrela i pruža dodatne informacije o međusobnoj zamenjivosti lekova, koje mogu biti od koristi u kliničkoj praksi, te predstavlja iskorak u pravcu primene alternativnih metoda u svrhu poređenja biološke raspoloživosti lekova kod kojih nije pogodan standardni pristup predviđen aktuelnom regulativom.Clopidogrel, a platelet aggregation inhibitor, is a prodrug that undergoes rapid absorption and extensive hepatic first-pass metabolism after p.o. administration. The majority of the dose is metabolized into the inactive metabolite clopidogrel carboxylic acid, while only about 15% is converted into the active metabolite clopidogrel thiol, responsible for the clopidogrel therapeutic effect. Given its variable pharmacokinetics and therapeutic response, understanding differences in the rate and extent of absorption between generic products is crucial, as these differences could potentially impact patient safety or therapeutic outcomes. Although generic products are individually bioequivalent to the reference drug, bioequivalence between generics has not been directly assessed. The dissertation aimed to address this gap through two main objectives. In the first part of the dissertation the aim was to compare the rate and extent of absorption between 19 generic clopidogrel drugs, using indirect and direct comparison methods, analyzing primary and/or secondary data for clopidogrel and clopidogrel carboxylic acid originated from the bioequivalence studies. The aim of the second part of the research was to characterize the process of absorption and disposition of clopidogrel, as well as its conversion to clopidogrel carboxylic acid, through the development and validation of a joint population pharmacokinetic model, considering also variability factors. Clopidogrel and clopidogrel carboxylic acid concentrations as well as other available relevant primary data from two bioequivalence studies were used for model development. Data for clopidogrel and clopidogrel carboxylic acid from 19 bioequivalence studies were analyzed using adjusted indirect comparison method, which allowed the identification of combinations of generic clopidogrel drugs that can be considered mutually bioequivalent and potentially interchangeable in clinical practice (76%), as well as those for which substitution is not recommended. A direct comparison of pharmacokinetic parameters from two bioequivalence studies using Student t-test showed similarity between the generic drugs from these studies in the extent of clopidogrel absorption and its conversion to clopidogrel carboxylic acid, but not in terms of the rate of these processes. Since the extent of absorption is clinically more important compared to the rate of this process, these differences were deemed not statistically significant. A joint semi-physiological population pharmacokinetic model for clopidogrel and clopidogrel carboxylic acid was developed and validated using the nonlinear mixed effects modeling approach. Model included linear absorption with 2 transit compartments, hepatic compartment for describing clopidogrel presystemic metabolism to metabolites, one-compartment model for clopidogrel, two-compartment model for clopidogrel carboxyl acid, linear elimination of this metabolite, allomeric scaling of clearance and volume of distribution. The developed model provides a solid base for potential future improvements in building a more complex model. This research uses state-of-the-art methods for analyzing secondary and/or primary data available for generic clopidogrel drugs and provides additional information on interchangeability of these drugs, especially for cases where traditional regulatory approaches may not suffice. It provides additional data that can inform clinical decision-making and optimize the use of generic clopidogrel products in practice

Validation of the fermented food frequency questionnaire to assess consumption across four European regions: a study within the promoting innovation of fermented foods cost action

Background: Fermented foods are an integral part of diets worldwide, and emerging epidemiological data suggest their significant beneficial health effects. However, assessing their intake is challenging since many of these foods are sporadically and/or locally consumed, hence current traditional nutritional assessment tools lack the specificity to capture this variability. To address this gap, the Fermented Food Frequency Questionnaire (3FQ) was developed and this study aimed to evaluate its relative validity and repeatability across European regions. Methods: In the validation study of the 3FQ, 12,646 adult participants were recruited across four European regions to assess consumption of sixteen major fermented food groups. Repeatability was assessed by administering the 3FQ twice, ~6 weeks apart, to a subset of participants (n = 2,315). Validity was evaluated using 24-h dietary recalls (24 h). Statistical analyses included Spearman's rank correlation coefficients and Intra-Class Correlation coefficients (ICC) for repeatability, and Bland-Altman plots for validity. Results: Results showed high repeatability, overall and by region, for estimated quantities and frequencies of consumption for most of the fermented food groups (from 0.4 to 1.0), with a few exceptions for infrequently consumed items (e.g., fermented fish). Validity assessment via Bland-Altman plots revealed excellent agreement between the 3FQ and 24 h for most of the food groups, with over 90% of values falling within the agreement interval. Notably, fermented dairy products, coffee, and bread categories showed the strongest agreement (>95%). Conclusion: The 3FQ is a robust and reliable tool for estimating the consumption of diverse fermented food groups across four European regions and provides valid estimates of the frequency and quantity of intake for specific fermented foods. The 3FQ could be a valuable instrument for epidemiological research aiming to elucidate associations between certain fermented foods and health parameters in European diets. Copyrigh