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Inovacije u 3D štampanim farmaceutskim oblicima lekova za pedijatrijsku populaciju - primer lozengi za žvakanje
No full textThree-dimensional (3D) printing offers a versatile platform for producing personalized,
age-appropriate dosage forms that address the specific therapeutic and administration needs of
the pediatric population. Among several oral dosage forms that can be prepared by 3D printing,
chewing lozenges offer numerous advantages, especially for the pediatric population. This study
illustrates a formulation development and selection of process parameters for 3D-printed chewing
lozenges containing propranolol hydrochloride as a model drug, with potential application in the
pediatric population. It also highlights the advantages of 3D printing using the semi-solid material
extrusion method.
Gelatin and sodium alginate were used as carriers for 3D printing. Immersion time in the
calcium chloride solution (tim) and lozenges shape were varied, while the following tests were
performed: the assessment of organoleptic properties, mass and thickness variations, melting and
disintegration time, drug content and dissolution rate.
Initially, the key 3D printing parameters for lozenge production were identified, and then
the appropriate formulation was selected. Subsequent testing demonstrated that the shape of
lozenges, along with variations in tim, influenced the pharmaceutical-technological characteristics.
A formulation based on the combination of gelatin and sodium alginate in 1:3 ratio, immersed for
60 seconds in a calcium chloride solution, was found to be suitable for 3D printing of chewable
lozenges.Trodimenzionalna (3D) štampa pruža široku platformu za proizvodnju personalizovanih farmaceutskih oblika prilagođenih uzrastu, koji odgovaraju specifičnim terapijskim potrebama pedijatrijske populacije. Među različitim oralnim farmaceutskim oblicima koji se mogu pripremiti pomoću 3D štampe, lozenge za žvakanje nude brojne prednosti, naročito za pedijatrijske pacijente. Ovaj rad prikazuje razvoj formulacije i izbor procesnih parametara za 3D-štampane lozenge za žvakanje koje sadrže propranolol-hidrohlorid kao model supstancu, sa potencijalnom primenom u pedijatrijskoj populaciji. Takođe, ističu se prednosti 3D štampe korišćenjem metode ekstruzije polučvrstog materijala. Želatina i natrijum-alginat korišćeni su kao nosači za 3D štampu. Varirani su vreme uranjanja u rastvor kalcijum-hlorida (tim) i oblik lozengi, pri čemu su sprovedena sledeća ispitivanja: procena organoleptičkih svojstava, variranje mase i debljine, vreme topljenja i raspadljivost lozengi, sadržaj i brzina rastvaranja propranolol-hidrohlorida. U početnoj fazi identifikovani su ključni parametri 3D štampe za izradu lozengi, a zatim je odabrana odgovarajuća formulacija. Dalja ispitivanja su pokazala da oblik lozengi, u kombinaciji sa varijacijama u vremenu uranjanja, utiče na farmaceutsko-tehnološke karakteristike izrađenih preparata. Formulacija zasnovana na kombinaciji želatine i natrijum-alginata u odnosu 1:3, uronjena 60 sekundi u rastvor kalcijum-hlorida, pokazala se pogodnom za 3D štampu lozengi za žvakanje
The second victim experience and support tool: a cross-cultural adaptation, validation and psychometric evaluation of the Serbian version for pharmacy professionals (SR-SVEST-R)
No full textBackground: The second victim phenomenon, involving emotional and psychological distress after adverse events, is underexplored among pharmacy professionals. The validated Second Victim Experience and Support Tool measures these experiences and support options, with the improved version also assessing resilience. Aim: This study aimed to validate the Second Victim Experience and Support Tool-Revised, measure the second victim phenomenon, and present results among pharmacy professionals in Serbia. Method: This cross-sectional study included 350 pharmacy professionals (MPharm and technicians). The questionnaire, with 9 factors and 35 statements, was translated and adapted following guidelines, and the content was validated by five experts. A pre-test with 30 participants ensured clarity, followed by Confirmatory Factor Analysis for construct validity and Cronbach's Alpha for reliability. Results: Content validity was confirmed with item scores from 0.8 to 1 and a mean scale score of 0.83. Factor analysis identified 9 factors and 30 items (Chi-square = 545.6, degrees of freedom = 366, p < 0.001). The model fit was supported by a Root Mean Square Error of Approximation of 0.037, a Comparative Fit Index of 0.958, a Tucker-Lewis Index of 0.950, and a Standardised Root Mean Square Residual of 0.040. Reliability analysis showed a Cronbach's alpha of 0.88, with factor values from 0.60 to 0.90. Among participants, 49.5% feared future events, 47.4% felt exhausted, 22.6% considered quitting, 72.6% valued peer support, and 28.9% improved work quality. Conclusion: The Serbian resilience measuring tool is valid and reliable, effectively evaluating second victim experiences and support, with half of pharmacy professionals affected
Vascular plant nano-hotspots in the central Balkan Peninsula – A novel GIS-based approach for identifying centres of species richness
No full textAlthough the Balkan Peninsula is one of the most biodiverse regions in Europe, there is still a lack of knowledge about its plant diversity. This study aimed to fill this knowledge gap by studying the spatial patterns of plant diversity on three massifs that had previously been identified as hotspots for endemics, Arctic-alpine and Boreal relics. To achieve this objective, we employed data gap and GIS analysis techniques to identify species-rich areas and to assess the relationship between taxa richness and the components of environmental heterogeneity. Targeted field surveys were carried out over two seasons, and a total of 97 environmental factors were selected as elements of environmental heterogeneity. A considerable number of hotspots of plant richness were identified, comprising 18 actual and 57 potential nano-hotspots. Most of the identified potential nano-hotspots are situated in areas characterized by a pronounced canyon or ravine formation, while the lowest number was observed at the highest elevations of the mountains, especially in regions where silicate substrates predominate. Our findings confirm the importance of factors previously identified as pivotal, including terrain ruggedness, topoclimate, elevation, geological substrate, and vegetation types, and for the first time suggest that hydrographic factors exert a strong influence on patterns of species richness. Given the considerable taxa richness observed in the ravine habitats of the study area, which makes them of high conservation value, it is essential to implement robust protective mechanisms to mitigate the impending effects of global warming and carefully plan the construction of hydropower plants
Microbial nanocellulose as an effective lactonase immobilization matrix for enhanced wound healing
No full textChronic wounds pose a significant challenge due to bacterial biofilm infections and antibiotic resistance. Quorum-quenching enzymes like lactonases offer a promising therapeutic alternative. In this study, bacterial nanocellulose (BNC) is investigated as a biocompatible matrix for immobilization of YtnP lactonase, aiming to increase its efficacy against Pseudomonas aeruginosa. Two methods were employed: covalent cross-linking with glutaraldehyde (BNCL) and coordination with zinc ions (BNCML). Fourier transform infrared spectroscopy confirmed enzyme-matrix interactions, while differential scanning calorimetry and rheological analyses confirmed the stability of the immobilized enzyme. Both BNCL and BNCML preparations retained their activity when reused ten times and showed no significant loss of function after three months at +4 °C, while the free enzyme lost over 40 % of its initial activity. In a mouse wound model infected with P. aeruginosa, treatment with BNCL reduced the number of neutrophils, NK cells, and pro-inflammatory M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages, which accelerated wound closure compared to untreated controls. In contrast, BNCML had a negative effect on healing. These results highlight BNC as a stable and biocompatible matrix for the immobilization of lactonase, making BNCL a promising infection-inhibiting alternative to conventional antimicrobial therapies for the treatment of chronic wounds
Teucrium montanum Essential Oils Variability in the Balkan Peninsula
No full textTeucrium montanum is an evergreen shrub that is widespread in Europe. The aim of this study was to determine the composition of the essential oils of T. montanum and their relationship to ecology, morphology and genetics. The essential oils were analysed by gas chromatography–mass spectrometry and the data were evaluated by multivariate statistics and multiple regression. This species showed a remarkable variability of essential oils in the Balkan Peninsula. All registered compounds were used to define four chemotypes that showed no spatial regularity and did not correlate with most bioclimatic parameters. The classification of samples into chemotypes and different categorical variables proved to be completely independent. Moreover, the identified compounds showed no correlation with the bioclimatic parameters, including other categorical variables. To study such a complex phenomenon as the variation of essential oils of T. montanum, a different sampling approach must be adopted (e.g., ‘one individual, one sample’), but this could affect the viability of the population of this species
Phytochemical characterization and antioxidant potential of methanol extracts of two Stachys species
No full textIn this study, phytochemical profile and antioxidant activity of dry methanol extracts from aerial flowering parts of two species from the Stachys subsect. Rectae R. Bhattacharjee were analysed. Stachys angustifolia M. Bieb. is a Pontic plant that inhabits steppe and steppe-like grass communities in Ukraine, Romania and the E. Balkans. Stachys goulimyi Rech. f. is an stenoendemic ultramafic orophyte from Mt Vourinos in N.W. Greece. Plants were collected from natural habitats in Bulgaria (Melnik, Rožen) and Greece, respectively. Air-dried, powdered plant material was successively extracted with chloroform and methanol. The resulting dry methanol extracts were analyzed using liquid chromatography coupled to mass spectrometry (LC-MS), revealing a complex composition of phenolic acids, phenylethanoid, flavonoid (primarily isoscutellareine and hypolaetine derivatives), and iridoid glycosides. Results demonstrated significant differences among species, with extract of S. goulimyi being particularly rich in flavonoids (56.62%) and extract of S. angustifolia being devoid of any phenylethanoid glycosides. Main compound in both extracts was isoscutellarein-7-O-[6'''-acetylallosyl(1®2)]-glucopyranoside (41.07 and 8.87%, respectively). Antioxidant activity was evaluated using spectrophotometric DPPH and FRAP assays, and correlated with phenolic composition. Obtained results provide new insights into phytochemical diversity and bioactive potential of underexplored Stachys taxa, supporting their relevance for further pharmacological and phytochemical studies
First bioconjugates in the role of highly effective human dihydroorotate dehydrogenase inhibitors: Synthesis, pharmacological, toxicological and hydrolytic stability studies of α-amino acid-modified pyrrolo[3,4-c]quinoline-1,3-dione scaffold
No full textHuman dihydroorotate dehydrogenase (hDHODH) represents an attractive target for the treatment of cancer, diabetes, anti-infective and autoimmune diseases. In drug development, hDHODH inhibitors with great potency, good chemical stability and low toxicity open the broad therapeutic perspectives. Accordingly, this study identified the first bioconjugates as highly effective compounds in inhibition of hDHODH. Pyrrolo[3,4-c]quinoline-1,3-dione scaffold was modified with the selected α-amino acids in a new simple synthetic protocol giving the desired derivatives in good yields and high purity. Tyrosine bioconjugate 4g was found to be the most potent hDHODH inhibitor (IC50 = 32 nM) with an excellent cytotoxic profile on the healthy HaCaT cells and favorable lipophilicity. In the experiments with enzymes simulating oral, gastric and duodenal digestion, 4g demonstrated good resistance to degradation providing a sufficient level of bioavailability. In addition, the objective of the study was to evaluate the comparative differences in toxicological effects between the 4g and leflunomide on rat liver and kidney injury markers and parameters of redox homeostasis in erythrocytes. The bioactive conformation of 4g on the hDHODH, determined using molecular docking, highlighted key interactions within the hDHODH binding site and provides a rational basis for further optimization
Application of machine learning and molecular docking to the modelling and design of HDAC6/ROCK dual inhibitors with in vitro experimental validation
No full textBackground & Aims: Biliary tract cancer (BTC) is a rare but aggressive malignancy
with limited treatment options and poor prognosis, necessitating novel therapeutic
strategies. Histone deacetylases (HDACs) play a critical role in the epigenetic
regulation of BTC progression, and HDAC inhibitors have shown promise in preclinical
studies. However, their clinical efficacy as monotherapies remains limited, driving the
exploration of multitarget approaches. Recent studies by Djokovic et al. highlight the
potential of combining HDAC and Rho-associated protein kinase (ROCK) inhibitors as
an antimetastatic strategy. This study aimed to develop machine learning (ML) models
for predicting the activity of HDAC6 and ROCK2 inhibitors and to apply these models
in the design and evaluation of novel dual HDAC/ROCK inhibitors.
Materials & Methods: Datasets for HDAC6 and ROCK2 inhibitors were extracted from
the ChEMBL database, preprocessed, and used to calculate 2D molecular descriptors.
Predictive models were developed using random forest regression to establish
quantitative structure–activity relationship (QSAR) models for both targets. The models
were applied for virtual screening of newly designed dual inhibitors, followed by
molecular docking studies to assess binding potential.
Results: The ML-driven QSAR models demonstrated high predictive accuracy for
HDAC6 and ROCK2 inhibitors. Virtual screening identified promising dual
HDAC/ROCK candidates, which were further evaluated through molecular docking.
The top candidates were synthesized and tested in enzyme assays confirming a lead
compound with potent activity, accurately predicted by the ML models. Further in vitro
studies in BTC cell lines are ongoing to assess anticancer efficacy.
Conclusion: This study presents an ML-guided approach for the rational design of
dual HDAC6/ROCK inhibitors, offering a promising therapeutic strategy for BTC. The
integration of computational modeling with experimental validation demonstrates the
potential of AI-driven drug discovery in oncology.Monothematic Conference, Liquid Biopsy in BTC: from bench to bedside, May 22-23, 2025, Mallorca, Spai
Cholinergic system in patients with chronic kidney disease: cognitive and renal implications
No full textCholinergic synapses are widespread throughout the human central nervous system. Their high
density in the thalamus, neocortex, limbic system, and striatum suggests that cholinergic
transmission plays a vital role in memory, attention, learning and other higher cognitive functions.
As a result, the brain’s cholinergic system occupies a central position in research on normal
cognition and age-related cognitive decline, including dementias such as Alzheimer’s disease. In
addition to its role in the brain, neuronal cholinergic pathways are essential for the physiological
regulation of bodily organs, including the kidneys, through the parasympathetic branch of the
peripheral nervous system. Chronic kidney disease (CKD) is a non-communicable disease with a
global prevalence of approximately 10%. Cognitive impairment is common among patients with
CKD, with reported prevalence rates ranging from 30% to 60%, depending on definitions and
assessment methods used. Given the importance of the cholinergic system in cognitive processes, it
may be a key area of focus for evaluating cognitive function in this population. In this current
narrative review, we will first examine evidence linking the cholinergic system to cognitive functions; with a specific focus on drugs that affect this system. we will then discuss the potential
implications of cholinergic function in patients with CKD.This is peer-reviewed version of the following article: Xu, H.; Eriksdotter, M.; Hafez, G.; Mitra, S.; Bruchfeld, A.; Pešić, V.; Unwin, R.; Wagner, C. A.; Massy, Z. A.; Zoccali, C.; Pepin, M.; Capasso, G.; Liabeuf, S.; Capasso, G.; Andrade, A.; Arici, M.; Bachmann, M.; Bailey, M.; Barbieri, M.; Bobot, M.; Bruchfeld, A.; Arune-Bumblyte, I.; Rastenytė, D.; Calcutta, A.; Capolongo, G.; Carriazo, S.; Ceccarelli, M.; Covic, A. C.; De, A.; Delgado, P.; Endlich, N.; Endres, M.; Esposito, F.; Farisco, M.; Faucher, Q.; Ferreira, A. C.; Figurek, A.; Fouque, D.; Franssen, C.; Fridolin, I.; Frische, S.; Garneata, L.; Gesualdo, L.; Giannakou, K.; Godefroy, O.; Golenia, A.; Goumenos, D.; Jiménez, E. G.; Hafez, G.; Hoorn, E.; Silva, P. H. I.; Izhar, R.; Kelly, D.; Kesler, S.; Klimkowicz-Mrowiec, A.; Knauss, S.; Kurganaite, J.; Levassort, H.; Liabeuf, S.; Malyszko, J.; Mani, L.-Y.; Martino, G.; Massy, Z.; Mayer, C.; Mucci, A.; Mutevelic-Turkovic, A.; Nielsen, R.; Nitsch, D.; Ortiz, A.; Panagiotopoulos, V.; Karasavvidou, D.; Paolisso, G.; Pejušković, B.; Pepin, M.; Perna, A.; Perrottelli, A.; Pešić, V.; Pezzella, P.; Rroji molla, M.; Rychlík, I.; Sakkas, G.; Simeoni, M.; Romeo, M. J. S.; Spasovski, G.; Starčević, A.; Tedeschi, G.; Trevisani, F.; Unwin, R.; Vazelov, E.; Wagner, C. A.; Wagner, F.; Wanner, C.; Wiecek, A.; Zacchia, M.; Zacharia, L.; Zecchino, I.; Zoccali, C.; Mattace-Raso, F.; Endlich, K.-H.; Perico, N.; Remuzzi, G.; Trepiccione, F.; Okusa, M.; Marzo, V. D.; Blankestijn, P.; Eckardt, K.-U.; Konig, M.; Gansevoort, R.; Askari, H.; Hansen, B.; Snaedal, S.; Cuiban, E.; Caporusso, E.; Re, V. L.; Roiser, J.; Rosenberg, K.; Bisecco, A.; Denby, L.; Kulkarni, O. P.; Sharma, K.; Debnath, S.; Jaafar, A.; Capasso, A.; Mulholland, M.; Workeneh, B.; Iervolino, A.; Fraser, S.; Frey-Wagner, I.; Pastore, A.; Mačiulaitis, R.; De Donato, A.; Farinha, A. Cholinergic System in Patients with Chronic Kidney Disease: Cognitive and Renal Implications. Nephrology Dialysis Transplantation 2025, 40 (11), 2026–2037. [https://doi.org/10.1093/ndt/gfaf029
