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Predictive analysis of lipidome patterns in gestational diabetes mellitus risk assessment
No full textGestational diabetes mellitus (GDM) is the most common pregnancy compli‑ cation, affecting up to 25% of pregnancies world‑ wide.1 Along with disrupted glucose regulation, GDM is characterized by dyslipidemia.2 Despite extensive research into the role of routine lipid parameters, more comprehensive research into the lipidomic milieu in GDM offers promising op‑ portunities for deeper insights into pathogenet‑ ic mechanisms and risk assessment. ..
Strawberry and Drupe Fruit Wines Antioxidant Activity and Protective Effect Against Induced Oxidative Stress in Rat Synaptosomes
No full textThe aim of this study was to investigate the antioxidant capacity of fruit wines and their protective effects against hydrogen peroxide-induced oxidative stress in rat synaptosomes in vitro. The wines were produced from strawberries and drupe fruits (i.e., plum, sweet cherry, peach, and apricot) through microvinification with a pure S. cerevisiae yeast culture. Fruit wines were produced with and without added sugar before the start of fermentation, whereas subvariants with and without pits were only applied to drupe fruit wines. First, synaptosomes were treated with the wines, while oxidative stress was induced with H2O2. Subsequently, the activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of malondialdehyde (MDA), an indicator of membrane injury, were determined. In addition, the Briggs–Rauscher reaction (BR) was used to evaluate the inhibition capacity against free radicals. All investigated fruit wines increased the activity of the studied antioxidant enzymes and decreased MDA content compared to the corresponding controls (synaptosomes treated with H2O2). After synaptosomal treatment with plum wine, the highest activities were observed for SOD (5.57 U/mg protein) and GPx (0.015 U/mg protein). Strawberry wine induced the highest CAT activity (0.047 U/mg protein) and showed the best ability to reduce lipid peroxidation, yielding the lowest MDA level (2.68 nmol/mg). Strawberry, plum, and sweet cherry wines were identified as samples with higher antioxidant activity in both principal component analysis (PCA) and hierarchical cluster analysis (HCA). Finally, plum wine exhibited the highest inhibitory activity in the BR reaction (397 s). The results suggest that fruit wines could be considered potential functional food due to their protective effects against oxidative stress
Genetska predispozicija za razvoj karcinoma jajnika
No full textOvarian cancer is a leading malignancy in the female reproductive system and is
responsible for more deaths than any other type of cancer affecting this system. Ovarian cancers
can be hereditary or sporadic. Anatomic, cellular, microenvironmental and molecular features of
ovarian cancers show a high degree of heterogeneity. Numerous genes implicated in the
pathogenesis and progression of ovarian cancers have been identified to date. The majority of
these genes act as tumour suppressor genes, oncogenes, or are involved in mismatch repair and
double-strand break repair mechanisms. The identification of mutations in cancer susceptibility
genes could be a major step forward towards earlier diagnosis, personalized therapy approaches
and outcome monitoring. In healthy women, detecting a specific mutated gene can provide a
rationale for personalized surveillance, chemopreventive strategies, and prophylactic surgery.
Next-generation sequencing offers comprehensive genome analysis, which enables profound
understanding and identification of cancer susceptibility genes, and new molecular diagnostic
markers and therapeutic targets.Rak jajnika je malignitet ženskog reproduktivnog sistema koji je, uzimajući u obzir visok
stepen agresivnosti i otkrivanje u kasnijim stadijumima, uzrok najvećeg broja smrtnih slučajeva
u poređenju sa bilo kojim drugim malignim tumorom ženskog reproduktivnog sistema. Rak
jajnika može biti nasledan ili stečen. Anatomske, ćelijske i molekularne karakteristike karcinoma
jajnika pokazuju visok stepen heterogenosti. Do sada su identifikovani mnogi geni uključeni u
patogenezu i napredovanje karcinoma jajnika. Većina ovih gena funkcionišu ili kao tumor
supresorski geni, onkogeni, geni uključeni u popravku pogrešno sparenih baza u DNK ili
dvolančanih prekida u DNK molekulu. Identifikacija specifičnih mutacija u genima koji mogu
biti uzročnici raka jajnika predstavlja napredak koji bi omogućio pravovremenu dijagnozu,
individualni pristup terapiji i preciznije praćenje ishoda pacijenata. Kod zdravih žena,
identifikovanje mutacije u genima koji mogu doprineti nastanku kancera ovarijuma bi omogućilo
intenzivnije usmeravanje ka pojačanom nadzoru tih žena, ili bi pružilo indikaciju za
hemopreventivne pristupe i profilaktičku hirurgiju. Sekvenciranje sledeće generacije nudi
sveobuhvatnu analizu genoma, koja omogućava duboko razumevanje i identifikaciju gena koji
mogu biti u osnovi patogeneze raka jajnika, kao i nove molekularne dijagnostičke markere i
terapijske ciljeve
Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids
No full textThe retention behavior of 10 previously synthesized α,β-unsaturated acids that exhibited antimicrobial activity was studied using 12 reversed-phase thin-layer chromatography (RP-TLC) systems. The mobile phases consisted of three solvent combinations (methanol‒water, acetonitrile‒water, and acetone‒water) in four different ratios (50:50, 60:40, 70:30, and 80:20, V/V). The chromatographic parameters RM0, a, and C0 were calculated for each system. The lipophilicity parameters of the tested compounds were predicted using various computational methods. The acetone‒water system demonstrated the highest correlation coefficients between the chromatographic and calculated lipophilicity parameters, which makes it the most suitable for evaluating the lipophilicity of the tested compounds. This system successfully reflected the effect of the lipophilic properties of the compounds on their retention behavior. To elucidate the retention mechanisms, the molecular properties of the tested compounds were calculated and a genetic algorithm was used to identify the properties with the greatest influence on the retention behavior. The interpretation of these descriptors revealed structural and physicochemical properties crucial for the behavior of the tested compounds. In addition, the pharmacokinetic properties of the compounds were estimated using in silico methods. The observed correlation between the retention mechanism and physicochemical properties affecting membrane transport and physiological binding ability highlights the applicability of RP-TLC conditions for rapid profiling of newly synthesized α,β-unsaturated acid
Cathepsin B: Plasma Expression and Concentration in Non-Hodgkin Lymphoma Patients
No full textNumerous studies point to the significance of cathepsin B (CTSB) in the development of carcinoma. Therefore, the aim of this pilot study was to investigate the levels of cathepsin B (CTSB) and the expression of CTSB mRNA in the plasma of non-Hodgkin lymphoma (NHL) patients. Methods: The study included 44 newly diagnosed NHL patients and 35 healthy volunteers comprising the control group. CTSB in the plasma samples were detected using the enzyme-linked immunosorbent assay (ELISA). Results: The level of CTSB was significantly higher in NHL patients compared to control subjects: 15.28 (11.68–17.23) versus 11.57 (10.12–13.41), p = 0.003. In addition, a positive correlation between plasma CTSB mRNA and CTSB after therapy was observed (rho = 0.591, p = 0.026). Regarding redox parameters, we found a negative correlation between CTSB and the total antioxidant status (TAS) (rho = −0.499, p = 0.035), as well as a positive correlation with the total oxidant status (TOS) (rho = 0.576, p = 0.012). Conclusions: Targeting CTSB might have significant clinical relevance in the diagnostics of NHL
Comparative evaluation of the porosity of different liquisolid systems with atorvastatin calcium
No full textINTRODUCTION
Liquisolid systems (LSS) have proven to be a cost-effective approach to improve the bioavailability of poorly soluble drugs by a relatively simple process consisting of dispersing the solid drug in a suitable liquid and then converting the resulting liquid phase into a dry, non-sticky powder with the addition of carrier and coating material (Aleksić, 2022). Carriers are excipients characterised by high porosity and a large specific surface area, which allows them to absorb large quantities of liquid while retaining the appearance of a powder (Spireas, 2002). Depending on the type of carrier used, the ratio of carrier to coating material (R value) and the ratio of liquid phase to carrier (liquid load factor, Lf), tablets prepared from these formulations exhibit different wetting and disintegration properties which may affect drug release, drug absorption and eventual therapeutic effect (Lu, 2017). The aim of this study was to investigate the porosity of four different carriers and the influence that addition of liquid phase, coating material and other excipients have on the porosity of the LS tablets prepared with atorvastatin calcium as a model drug
Silver-doped bismuth ferrite: enhanced magnetization and theoretical predictions of novel perovskite phases
No full textIn 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
Dodaci ishrani u pedijatrijskoj populaciji u Srbiji - pregled najčešće primenjivanih proizvoda
No full textFood supplements (FS) are products intended to provide additional nutrients to the normal
diet. They contain concentrated amounts of nutritive and non-nutritive compounds with a
nutritional or physiological effects and are available in various dosage forms for ingestion in
small, defined quantities. In recent decades, FS have become increasingly popular among
children. When developing pediatric products, both the nutritional needs and the safety aspects
specific to this population group are considered. This report analyzes dietary supplements used
by children in Serbia, focusing on dosage, safety and the existence of official guidelines. The
analysis includes vitamins (D, K and B-complex), probiotics, omega-3 fatty acids, beta-glucans
and various herbal products. Although these supplements are widely used in Serbia, there are
official pediatric guidelines only for vitamin D, vitamin K, probiotics and omega-3 fatty acids.
Herbal supplements are particularly problematic due to insufficient data on safety, interactions
and possible side effects. Therefore, increased education of both parents and healthcare
professionals is essential to ensure appropriate intake, maximize health benefits and support the
proper and safe use of supplements in the pediatric population.Dijetetski suplementi (dodaci ishrani) su namirnice dizajnirane da dopune svakodnevnu ishranu. Oni sadrže koncentrovane izvore nutritivnih i nenutritivnih sastojaka sa hranljivim ili fiziološkim efektom i u prometu su u različitim farmaceutskim oblicima, namenjenim za konzumiranje u odmerenim pojedinačnim količinama. Poslednjih decenija, upotreba dijetetskih suplemenata je postala sve češća u pedijatrijskoj populaciji. Formulacije za decu su posebno dizajnirane kako bi se zadovoljile njihove nutritivne potrebe i specifični bezbednosni zahtevi. Ovaj pregledni rad sadrži analizu dijetetskih suplemenata koji su često u upotrebi kod dece u Srbiji, sa fokusom na doziranje, bezbednost i dostupnost zvaničnih smernica. Opisani su dijetetski suplementi koji sadrže vitamine (D, K i B kompleks), probiotike, omega-3 masne kiseline, beta-glukane i različite biljne preparate. Uprkos širokoj upotrebi u Srbiji, zvanične pedijatrijske smernice postoje samo za vitamin D, vitamin K, probiotike i omega-3 masne kiseline. Biljni suplementi i dalje predstavljaju poseban izazov zbog nedovoljno podataka o bezbednosti, interakcijama i potencijalnim neželjenim efektima. Uzimajući u obzir sve navedeno, neophodno je edukovati roditelje i zdravstvene radnike, kako bi se obezbedio adekvatan unos, osigurali optimalni zdravstveni efekti i omogućila bezbedna upotreba dijetetskih suplemenata u pedijatrijskoj populaciji
Corrigendum: The role of dendritic cells in tertiary lymphoid structures: implications in cancer and autoimmune diseases (Frontiers in Immunology, (2024), 15, (1439413), 10.3389/fimmu.2024.1439413)
No full textIn the published article, there was an error in the Funding statement. The section originally stated that “COST is supported by the EU Framework Program Horizon 2020”, while it should refer to “Horizon Europe”. The correct Funding statement appears below. “The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was developed within the scope of projects with references UIDB/04501/2020 and https://doi.org/10.54499/UIDB/04501/2020, UIDP/04501/2020 and https://doi.org/10.54499/UIDP/04501/2020, 2022.03217.PTDC and DOI 10.54499/2022.03217.PTDC, financially supported by national funds (OE), through FCT - Fundação para a Ciência e Tecnologia, I.P./MCTES. This work was also supported by the World Scleroderma Foundation and Edit Busch Stiftung (MAPFib). This work has been supported by Ministry of Science, Technological Development and Innovation, Republic of Serbia through Grant Agreement with University of Belgrade, Faculty of Medicine No: 451-03-66/2024-03/200110. This work was funded by the Ministry of Science, Technological Development and Innovation, Republic of Serbia through Grant Agreement with University of Belgrade-Faculty of Pharmacy No: 451-03-47/2023-01/200161. This work was supported by the Wellcome Trust (225021/Z/22/Z). This work was supported by the Swedish Cancer Society (22 2221.Pj.01.H) and Mrs. Berta Kamprad’s Cancer Foundation (FBKS-2022-8-368). This work was supported by the Scientific and Technological Research Council of Turkey- TUBITAK (119S447 and 22AG077). This work was also supported by European Cooperation in Science and Technology (COST) Action CA20117 Mye-InfoBank (www.mye-infobank.eu); COST is supported by the EU Framework Program Horizon Europe.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.Link to the corrected article: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/5830
Population pharmacokinetics of linezolid and correlation with efficacy and safety parameters in patients with acute respiratory distress syndrome on veno-venous extracorporal membrane oxygenation
No full textVeno-venska ekstrakorporalna membranska oksigenacija (V-V ECMO) je sve više zastupljena u zbrinjavanju respiratorne insuficijencije kod kritično oboljelih. Ipak, uticaj ovog oblika terapijske podrške na farmakokinetiku (FK) i doziranje lijekova, posebno linezolida, još uvijek nije dovoljno istražena oblast. Cilj istraživanja je da se procijeni opravdanost primjene viših doza linezolida, u poređenju sa standardnim, kod kritično oboljelih sa akutnim respiratornim distres sindromom (ARDS) uzrokovanim COVID-19, koji su istovremeno bili na V-V ECMO podršci. U istraživanje su prospektivno uključeni bolesnici sa dijagnostikovanim COVID-19 i ARDS uz terapijski model vvECMO podrške sa istovremenom intravenskom primjenom linezolida 600 mg/8 h. Kriterijumi za isključivanje su bili: osobe mlađe od 18 godina, poznata alergija na linezolid, trudnoća, terapijska izmjena plazme u posljednjih 24 sata i nadomjesna bubrežna terapija. Za analizu FK linezolida od svakog bolesnika u stanju ravnoteže lijeka prikupljeno je po šest uzoraka krvi u definisanim vremenskim tačkama. Prikupljeni su svi demografski i klinički podaci neophodni za procjenu uticaja istih na FK linezolida. Nelinearnim modeliranjem kombinovanih efekata razvijen je i validiran populacioni FK model, korišten za Monte Karlo simulacije (5000 virtualnih bolesnika) za generisanje individualnih FK parametara i koncentracijskih profila nakon režima doziranja 600 mg/8 h i 600 mg/12 h. Za procjenu vjerovatnoće postizanja ciljnih vrijednosti farmakokinetičkog-farmakodinamičkog (FK-FD) indeksa (PTA) korišteni su sljedeći targeti: 85%T>MIC, fAUC24/MIC≥80 i fAUC24/MIC≥100. Izračunata je i kumulativna frakcija odgovora (CFR) za različite Gram-pozitivne bakterije. Praćeni su i bezbjednosni aspekti na osnovu promjene nivoa trombocita i razvoj trombocitopenije u odnosu na vrijeme započinjanja vvECMO i linezolida uz istovremenu primjenu. Ukupno su analizirane 53 koncentracije linezolida. Pokazana je visoka korelacija izmjeđu Cmin i AUC24. FK parametri linezolida nisu značajno odstupali u odnosu na ne-ECMO bolesnike i nije pronađen značajan uticaja kovarijata na FK parameter. Nakon doznog režima linezolida 600 mg/8 h predviđeno je jednako i veće postizanje FK-FD ciljne vrijednosti 85%T>MIC za MIC=2 mg/L kod 90%, dok je kod bolesnika koji su primali standardni dozni režim 85%T>MIC zabilježen kod dvije trećine bolesnika. fAUC24/MIC≥80 postignut je kod skoro tri puta većeg broja bolesnika primjenom linezolida 600 mg/8 h za istu vrijednost MIC-a. Prisustvo trombocitopenije sa značajnim smanjenjem broja tombocita zabilježeno je kod ukupno 81,8% bolesnika. Rezultati istraživanja ukazaju da dozni režim linezolida 600 mg/8 h u odnosu na standardni ima prednost kod istovremene primjene vvECMO terapijskog modela za postizanje FK-FD ciljnih vrijednosti linezolida i dobijanja adekvatnog terapijskog odgovora. Terapijsko praćenje koncentracije linezolida u serumu i broja trombocita je neophodno kako bi se zadovoljili bezbjednosni aspekti uz maksimalan terapijski efekat linezolida kod kritično oboljelih sa ARDS na V-V ECMO podršci.Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is increasingly used in managing respiratory failure in critically ill patients. However, the impact of this form of therapeutic support on the pharmacokinetics (PK) and dosing of medications, especially linezolid, remains an insufficiently explored area. This study aims to evaluate the rationale for administering higher doses of linezolid, compared to standard doses, in critically ill patients with acute respiratory distress syndrome (ARDS) caused by COVID-19, who are concurrently supported by V-V ECMO. The study prospectively included patients with COVID-19, ARDS, on a therapeutic V-V ECMO support model with concurrent intravenous administration of linezolid 600 mg every 8 hours. Exclusion criteria were: individuals under 18 years, known allergy to linezolid, pregnancy, therapeutic plasma exchange in the last 24 hours, and renal replacement therapy. For the analysis of linezolid PK, six blood samples were collected from each patient at steady state at defined time points. All demographic and clinical data necessary for assessing their impact on linezolid PK were collected. A population PK model was developed and validated using nonlinear modeling of combined effects, which was then employed in Monte Carlo simulations (5,000 virtual patients) to generate individual PK parameters and concentration profiles after dosing regimens of 600 mg every 8 hours and 600 mg every 12 hours. The probability of achieving target pharmacokinetic-pharmacodynamic (PK-PD) index values (PTA) was assessed using the following targets: 85%T>MIC, fAUC24/MIC≥80 i fAUC24/MIC≥100. The cumulative fraction of response (CFR) was also calculated for various Gram-positive bacteria. Safety aspects were monitored based on changes in platelet levels and development of thrombocytopenia in relation to the initiation of V-V ECMO and linezolid with concurrent application. A total of 53 linezolid concentrations were analyzed. A high correlation was found between Cmin and AUC24. Linezolid PK parameters did not significantly deviate from those in non-ECMO patients, and no significant impact of covariates on PK parameters was found. After the linezolid dosing regimen of 600 mg every 8 hours, the probability of achieving PK-PD target value of 85%T>MIC for MIC =2 mg/L was predicted to be 90%, while two-thirds of the patients on the standard dosing regimen reached 85%T>MIC. fAUC24/MIC≥80 was achieved in nearly three times more patients with the 600 mg every 8 hours linezolid regimen for the same MIC value. Thrombocytopenia occurred in 81.8% of patients with a significant reduction in platelet count. This study indicates that the linezolid dosing regimen of 600 mg every 8 hours, compared to the standard, is advantageous when using the V-V ECMO therapeutic model to achieve linezolid PK-PD target values and adequate therapeutic response. Therapeutic monitoring of linezolid serum concentrations and platelet counts is necessary to satisfy safety aspects while maximizing therapeutic effects in critically ill patients with ARDS on V-V ECMO