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Chemical composition and biological activity of Lycium barbarum L. i L. ruthenicum Murr. (Solanaceae) fruits grown in Serbia
No full textOsim primene u tradicionalnoj ishrani i medicini azijskih zemalja, plodovi vrsta Lycium (Solanaceae), poznati kao godži, kao i njihovi proizvodi se danas koriste u ishrani širom sveta. S obzirom na rastuće potrebe, vrste Lycium se sve više uzgajaju u Evropi, uključujući i Srbiju. U ovoj doktorskoj disertaciji izvršena je sveouhvatna analiza hemijskog sastava i bioaktivnog potencijala crvenih (Lycium barbarum L.), žutih (L. barbarum var. auranticarpum) i crnih (Lycium ruthenicum Murr.) plodova godži, kao i sporednih proizvoda prerade crvenih plodova godži (pulpe i pogače) gajenih u Srbiji.Analiza osnovnog nutritivnog sastava, sadržaja minerala, masnih kiselina, fitosterola i polifenola izvršena je standardnim, spektrofotometrijskim i hromatografskim metodama, dok su sadržaji bioaktivnih jedinjenja, kao i antioksidativni, antienzimski, antibakterijski i prebiotski potencijali u ekstraktima godži plodova određeni spektrofotometrijskim i vizuelnim metodama. Za optimizaciju procesa ekstrakcije odabranih sastojaka plodova i sporednih proizvoda prerade plodova godži korišćeni su Plackett-Burman i Box-Behnken eksperimentalni dizajn.Postoje značajne varijacije u hemijskom sastavu i biološkoj aktivnosti između plodova godži različitih biljnih vrsta, kao i između plodova godži sa različitih lokaliteta u Srbiji. Žuti plodovi godži imaju izraženiji antimikrobni potencijal, a crni plodovi godži se osim najizraženijeg antioksidativnog efekta, odlikuju i izraženim prebiotskim svojstvima. Analiza hemijskog sastava, kao i antioksidativni i antienzimski potencijal crvenih plodova godži, kao i njihovih sporednih proizvoda, nakon optimizacije ekstrakcije, ukazuju na mogućnost njihove primene u prehrambenoj i farmaceutskoj industriji.In addition to its use in Asian nutrition and traditional medicine, the fruits of the Lycium species (Solanaceae), known as goji berries, and their products are now used as food all over the world. Given the growing needs, there is rising interest in Lycium species cultivation in Europe, including Serbia. In this doctoral dissertation, a comprehensive analysis of the chemical composition and bioactive potential of red (Lycium barbarum L.), yellow (L. barbarum var. auranticarpum), and black (Lycium ruthenicum Murr.) goji berries, as well as by-products of red goji berries processing (pulp and press cake) grown in Serbia, was performed.The analysis of the proximate composition, minerals, fatty acids, phytosterols, and polyphenols was performed using standard, spectrometric, and chromatographic methods, while the contents of bioactive compounds, as well as antioxidant anti-enzymatic, antibacterial, and prebiotic potentials in goji berries extracts, were determined using spectrophotometric and visual methods. The Plackett-Burman and Box-Behnken experimental design was used to optimize the extraction process of selected components of the fruits and by-products of goji fruit processing.There are significant variations in the chemical composition and biological activity between goji fruits of different plant species and between goji fruits from different locations in Serbia. Yellow goji fruits have a more pronounced antimicrobial potential, and black goji fruits, in addition to a more pronounced antioxidant effect, are also characterized by pronounced prebiotic properties. Analysis of the chemical composition, the antioxidant and antienzyme potential of red goji fruits, and their by-products after optimization of the extraction indicate the possibility of their application in the food and pharmaceutical industries
Electrochemically cross-linked Zn-alginate films: new materials with antioxidant and antimicrobial activity
No full textThis study focused on the development of electrochemically cross-linked zinc–alginate films enriched with hyaluronic acid and/or oregano hydrolate, aiming to evaluate their antioxidant and antimicrobial properties in relation to composition
When conventional approach in toxicity assays falls short for nanomedicines: a case study with nanoemulsions
No full textThe aim of this study was to assess the critical quality attributes of parenteral nanoemulsion formulations by measuring several
physicochemical parameters and linking them to their in vitro performance, illustrating how simplistic and routinely used
approaches are insufficient for understanding a potential nanomedicine. Physicochemical characterization should encompass
size and size distribution through at least two orthogonal techniques, such as dynamic light scattering (DLS) and electron
microscopy, with added value from analytical ultracentrifugation. In vitro toxicity assessment was performed using three
different assays to determine mitochondrial activity (WST-1), membrane integrity (lactate dehydrogenase release (LDH)
assay), and cell viability (propidium iodide (PI) staining). Special focus was placed on estimating appropriate incubation times
for relevant results in biological investigations. All formulations had an average diameter of around 100 nm. Conclusions
regarding in vitro safety were assay-dependent: LDH and PI-based assays showed good correlation, while the WST-1 assay
indicated that the non-PEGylated formulation altered mitochondrial activity more significantly compared to the PEGylated
ones. The study underlined that the selection of appropriate cytotoxicity assays should be based on the possible mechanism
of cellular perturbation. Alternatively, different aspects of cellular toxicity should be tested. Additionally, there is a need for
well-designed controls to overcome nanoparticle scattering effects and avoid potentially false high toxicity results, which
was demonstrated. Combining orthogonal, well-designed physicochemical and biological assays in a standardized manner
as an initial step in the reliable preclinical characterization of nanomedicines is suggested. This represents a key aspect of
new methodologies in nanomedicine characterization
Kondo-Like Behavior in Lightly Gd-Doped Manganite CaMnO3
No full textManganese oxides (manganites) are among the most studied materials in condensed matter physics due to the famous colossal magnetoresistance and very rich phase diagrams characterized by strong competition between ferromagnetic (FM) metallic and antiferromagnetic (AFM) insulating phases. One of the key questions that remains open even after more than thirty years of intensive research is the exact conductivity mechanism in insulating as well as in metallic phases and its relation to the corresponding magnetic structure. In order to shed more light on this problem, here, we report magnetotransport measurements on sintered nanocrystalline samples of the very poorly explored manganites Ca1−xGdxMnO3 with x = 0.05 and x = 0.10, in the temperature range 2–300 K, and in magnetic fields up to 16 T. Our results indicate that both compounds at low temperatures exhibit metallic behavior with a peculiar resistivity upturn and a large negative magnetoresistance. We argue that such behavior is consistent with a Kondo-like scattering on Gd impurities coupled with the percolation of FM metallic regions within insulating AFM matrix
Precise Control of Structure and Magnetic Properties of BiFeO3: From Synthesis to Prediction of New Modifications
No full textIn 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
Intravenous nanoemulsions loaded with CW-02-79-phospholipid complex for enhanced brain delivery: physicochemical, in vitro and in vivo performances
No full textThis study addresses the challenge of poor solubility of novel psychopharmacological drug candidates (L/DCs) that hinders their development. ..
Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors
No full textChronic liver injury characterized by unresolved hepatitis leads to fibrosis, potentially progressing to cirrhosis and hepatocellular carcinoma. Effective treatments for halting or reversing liver fibrosis are currently lacking. This study investigates the potential of HDAC6 as a therapeutic target in liver fibrosis. We synthesized two selective HDAC6 inhibitors, DR-3 and FDR2, and assessed their effects on hepatic stellate cell (HSC) activation and liver fibrosis using human precision cut liver slices (hPCLS). Molecular docking, deacetylation inhibition assays, and various cellular assays were employed to evaluate the specificity and anti-fibrotic efficacy of these inhibitors. DR-3 and FDR2 demonstrated high selectivity for HDAC6 over HDAC1, significantly inhibiting HSC activation markers and fibrogenic gene expression. Both inhibitors increased acetylation of α-tubulin and suppressed TGF-β1-induced SMAD signaling in HSCs. In human precision cut liver slices (hPCLS), DR-3 and FDR2 reduced fibrogenic protein levels and collagen deposition. The selective inhibition of HDAC6 by DR-3 and FDR2 effectively reduces HSC activation and fibrogenesis in liver models, supporting further investigation of HDAC6 inhibitors as potential anti-fibrotic therapies
Faktorska analiza nivoa cinka u serumu, masnih kiselina, parametara oksidativnog stresa i suplementacije na rezultat potpomognute reproduktivne tehnologije
No full textBackground: Infertility remains a prevalent global reproductive challenge, significantly affecting the lives of couples worldwide. The aetiology of infertility can be affected
by various factors that exhibit possible relationships with
one another. The study aimed to investigate factors that
can interact with and influence the pregnancy outcome in
couples undergoing assisted reproductive technology procedures.
Methods: This retrospective study included 64 couples (64
men and their female partners) undergoing assisted reproductive technology procedures, having different pregnancy
outcomes and lifestyle habits. Biomarkers of antioxidative
and fatty acid status in the serum of both male and female
partners, as well as the concentration of zinc in serum and
seminal plasma of men, and their impact on assisted reproductive technology outcome were examined.
Results: We grouped the parameters using principal component analysis and identified the three most contributing
factors to the pregnancy achievement – seminogram
parameters in males and redox status scores in female participants; supplementation with vitamin D, magnesium,
and zinc; and serum levels of omega-3 and omega-6 fatty
acids.
Conclusions: The study concluded that seminogram
parameters, intake of micronutrients, and levels of zinc,
omega-3, and omega-6 fatty acids are contributing factors
to the success of assisted reproductive technology. Further
studies on a larger cohort are needed to confirm the predictive role of these factors on the success of assisted
reproductive technology.Uvod: Neplodnost je i dalje preovlađujući globalni reproduktivni izazov koji značajno utiče na živote parova širom
sveta. Na etiologiju neplodnosti mogu uticati različiti faktori
koji pokazuju moguće odnose jedni sa drugima. Cilj istraživanja bio je da se ispitaju faktori koji mogu da međsobno deluju i utiču na ishod trudnoće kod parova koji su
podvrgnuti postupku potpomognute reproduktivne tehnologije.
Metode: Ova retrospektivna studija obuhvatila je 64 parova
(64 mu{karaca i njihovih partnerki) koji su bili podvrgnuti
proceduri potpomognute reproduktivne tehnologije, sa
različitim ishodom trudnoće i životnim navikama. Ispitivani
su biomarkeri antioksidativnog i statusa masnih kiselina u
serumu muških i ženskih partnera, kao i koncentracija
cinka u serumu i u seminalnoj plazmi muškaraca; kao i
njihov uticaj na ishod potpomognute oplodnje.
Rezultati: Parametri su grupisani koristeći analizu glavnih
komponenti i identifikovali tri faktora koji najviše doprinose
uspešnosti oplodnje – parametri seminograma kod
muškaraca i redoks status skor kod žena; suplementacija
vitaminom D, magnezijumom i cinkom; i nivoi omega-3 i
omega-6 masnih kiselina u serumu.
Zaključak: Studija je zaključila da parametri seminograma,
unos mikronutrijenata i nivoi Zn i omega-3 i omega-6
PUFA doprinose uspehu potpomognute reproduktivne
tehnologije. Potrebne su dalje studije na većoj kohorti da bi
se potvrdila prediktivna uloga ovih faktora na uspeh
potpomognute reproduktivne tehnologije
Development and validation of a method for the separation and determination of the Z-isomer and N-demethyltamoxifen by thin-layer chromatography
No full textTamoxifen is a nonsteroidal selective estrogen receptor modulator (SERM), meaning that it acts as an anti-estrogen at estrogen receptors in certain tissues (breast tissue), while acting as an estrogen in other tissues (bone tissue and endometrium). The aim of this work was to establish thin-layer chromatography (TLC) conditions for the separation of Z-isomer of tamoxifen from its impurity F (N-demethyltamoxifen) and to validate the TLC method for the assay determination of impurity F in dosage forms. The method was validated according to the International Council for Harmonisation (ICH) Q2(R2) guidelines. Samples were spotted onto the TLC silica gel G F254 plate and developed in the saturated twin-trough chamber. The selected mobile phase was toluene‒cyclohexane‒triethylamine (65:25:20, V/V). The migration distances (28 mm and 64 mm for N-demethyltamoxifen and tamoxifen, respectively) with low relative standard deviation (RSD) values (2.59%) showed satisfactory reproducibility of the chromatographic system. The TLC Scanner was used for direct evaluation of the chromatograms in reflectance/absorbance mode. The calibration curves were generated (r = 0.998). The precision and detection limits as well as the recovery values (99.16‒101.02%) were validated and found to be satisfactory. On the basis of these results, it can be concluded that the developed TLC method is a rapid and efficient method for testing the purity of tamoxifen in bulk and pharmaceutical dosage forms
How effective is the implementation of the valproate pregnancy prevention programme in Montenegro? – A 7-year national retrospective study
No full textBackground: Valproate (valproic acid, sodium valproate) is authorised in Montenegro for
epilepsy and bipolar disorder treatment. Due to known teratogenicity, risk minimisation
measures were introduced in 2014 and further reinforced in 2018 by the implementation of the
Pregnancy Prevention Programme (PPP). Despite these measures, consumption of valproate
in Montenegro increased in the period 2016–2022.
Objectives: To investigate the effects of risk minimisation measures on valproate prescription
in Montenegro.
Design: A retrospective, observational, 7-year, nationwide study.
Methods: The Primary Health Care Information System (PHCIS) was used as a data source.
The health records of women of childbearing potential (12–55 years) for the period 2016–2022
were analysed. Additionally, unstructured data were reviewed to determine the number and
characteristics of valproate-exposed pregnancies. The software PASW, version 25.0 (SPSS
Inc., Chicago, IL, USA) was used for the statistical analysis.
Results: A total of 2247 women of childbearing potential using valproate were identified during
the observed period. The number of patients using valproate for epilepsy treatment decreased
by 24% while the use of valproate in psychiatry increased by 45% over the observed period.
The age of the patient was the only predictive factor for successful PPP implementation (chi-
square = 35.811, df = 4 and p < 0.001). The odds ratio (OR) for the age category was 1.22 (95% CI:
1.10–1.35). Contraception prescription was recorded in only 1.5% of patients following the PPP
implementation. A total of 11 cases of exposed pregnancies were identified, while epilepsy
was the indication in 5 (45%) cases.
Conclusion: Regulatory risk minimisation measures had a limited impact on reducing the risk
of valproate teratogenicity in Montenegro, with the most success in the group of youngest
patients. Measures were more effective in the epilepsy indication. The rising use of valproate
for psychiatric indications is concerning. Targeted education, better preconception care and
improved coordination among healthcare professionals are necessary