Procter & Gamble (United Kingdom)
Digital Repository of Archived Publications - Institute for Biological Research Sinisa Stankovic (RADaR)Not a member yet
7316 research outputs found
Sort by
Isorhamnetin Modulates Drug-Resistance-Related Biomarkers in Colon Cancer Cells
No full textThe development of resistance to standard cytostatics, such as 5-fluorouracil (5-FU), significantly
limits the efficacy of colon cancer therapy, prompting the search for novel anticancer
agents, particularly among natural compounds. This study evaluated the anticancer effects
of isorhamnetin, a plant-derived flavonol, and its ability to modulate the expression of
drug-resistance-related biomarkers in SW-480 and HT-29 colon cancer cells, with a focus on
ATP-binding cassette (ABC) transporters. Isorhamnetin demonstrated strong cytotoxic and
proapoptotic activity on both cell lines, while showing lower toxicity toward normal HaCaT
cells. In addition to suppressing the mRNA expression of drug-metabolizing enzymes
(CYP1A1 and CYP1B1), isorhamnetin significantly reduced the mRNA levels of multidrug
resistance-associated proteins 1 and 5 (MRP1 and MRP5), as well as the P-glycoprotein
(P-gp) level in SW-480 and HT-29 cells. Molecular docking analysis revealed a high binding
affinity of isorhamnetin to CYP1A1, CYP1B1, P-gp, MRP1, MRP5, and glutathione
S-transferase (GST) proteins, with stronger interactions than those observed for 5-FU, suggesting
potential interference with their function. These results provide a solid basis for
future investigations to confirm the therapeutic potential of isorhamnetin as a modulator
of drug resistance in colon cancer cells
Wild rodents as carriers of leptospirosis in areas of increased human presence
No full textFrom August 2019 to June 2020, research was conducted on the role of rodents as natural reservoirs
in the spread of zoonoses in eight selected localities in the territory of Vojvodina Province, Serbia. The
rodent sample included 134 individuals: Apodemus sylvaticus (31 individuals), A. agrarius (37),
A. flavicollis (62), Micromys minutus (1), Mus musculus (1), Microtus arvalis (1), and M. agrestis (1). As
part of the study, organ samples (heart and kidneys) of these species were tested for the presence of
Leptospira sp. bacteria. All samples were tested using real-time PCR method on the Genesig q16 device,
following the manufacturer's standard protocol with "Primerdesign" kits. The detection of Leptospira
sp. was conducted through the following procedures: (i) isolation-extraction of DNA from samples using
the commercial kit "Genesig easy DNA/RNA Extraction kit", and (ii) real-time PCR reaction using the
commercial kit "Leptospirosis Genesig easy kit", manufactured by "Primer design". The presence of
Leptospira sp. was confirmed in 12 individuals, namely 11 individuals of striped field mouse
(A. agrarius) from three lowland localities close to aquatic habitats, and in one yellow-necked mouse
(A. flavicollis) from an area of higher elevation. Leptospira sp. bacteria were detected in the kidneys,
which are the preferred site for these bacteria in all animals and humans. The obtained findings indicate
the existence of critical endemic areas for Leptospira sp. in the territory of Vojvodina Province, where
the occurrence of these diseases in humans is registered every year. The results are highly valuable
from an epidemiological point of view for the improvement of public health and are very important in
the context of applying the One Health approach to the problem of zoonotic diseases whose reservoirs
are mouse-like rodentsPokorny B, Flajšman K, Jacob J, editors. Book of abstracts: 14th European Vertebrate Management Conference; 2025 May 12-16; Ankaran, Slovenia. Ljubljana: Faculty of Environmental Protection, Slovenian Forestry Institute, University; 2025. p. 182
A simple alginate-based 3D in vitro model for preclinical anticancer drug evaluation
No full textThe development of novel anticancer drugs is a slow and costly process, with only 5 out of 5,000 compounds ultimately reaching the market. A major limitation lies in the low predictability of traditional preclinical methods, such as two-dimensional (2D) cell cultures and animal experiments, which often fail to replicate the cellular responses to drugs observed in patients. Therefore, three-dimensional (3D) in vitro models have emerged as valuable tools for drug screening. The aim of this study was to establish a 3D in vitro model based on alginate microfibers suitable for immobilizing various cancer cell types for anticancer drug testing. Murine osteosarcoma cells K7M2-wt (cell density: 4×106 cells cm-3) were immobilized in 2 wt.% Ca-alginate microfibers (diameter: 500−600 µm) with or without 2 wt.% hydroxyapatite (HAP) particles, while human non-small cell lung carcinoma cells NCI-H460 (cell density: 4×106 cells cm-3) were immobilized in 2 wt.% Ba-alginate microfibers (diameter ~ 550 µm) by manual extrusion. During long-term cultivation, cells in microfibers stayed viable and metabolically active, forming aggregates over time. Anticancer drug testing revealed that the half-maximal inhibitory concentration (IC50) values for 3D cultures of both K7M2-wt and NCI-H460 cells were up to 50-fold higher compared to those for 2D cultures. Additionally, the gene expression analysis showed a significant upregulation of drug resistance–related genes in 3D cultures. Overall, the obtained results align with the observed higher resistance to anticancer drugs in patients compared to traditional preclinical models, highlighting the potential of the proposed model to improve in vitro drug screening reliability.Diva Rankov A, editor. Abstract Book: Belgrade Conference for Early-Career Life Scientists: BeCELS 2025; 2025 Sep 5; Belgrade, Serbia. Belgrade: Institute of Molecular Genetics and Genetic Engineering, University; 2025. p. 9
First Record of Asian Nematode Heligmosomoides neopolygyrus Asakawa & Ohbayashi, 1986 (Rhabditida: Heligmosomidae) from Striped Field Mice Apodemus agrarius (Pallas, 1771) (Rodentia: Muridae) in Serbia
No full textIn two individuals of Apodemus agrarius out of the 41 studied specimens of this species, specific taxonomic characters reminiscent of those of Heligmosomoides neopolygyrus were noted in heligmosomid
nematodes. Morphological identification and comparative phylogenetic analyses were performed based
on cytochrome b sequences of Heligmosomoides isolated from Apodemus agrarius. Morphological traits
confirmed that these two nematodes were H. neopolygyrus. Phylogenetic analysis showed clustering of
Serbian sequences of H. neopolygyrus from A. agrarius and also clustering of these sequences with those
of H. neopolygyrus from A. agrarius from Poland and A. uralensis from Russia. This is the first report of
the presence of Heligmosomoides neopolygyrus in Serbia
Metal exclusion and physiological plasticity shape orchid success across diverse geologies
No full textEdaphic stress is a major factor influencing plant fitness, yet it remains insufficiently understood, especially
in rare species like orchids. Orchids, with their complex ecological requirements and sensitivity to soil
chemistry, provide valuable models for studying adaptations to contrasting geologies. We investigated the
ecophysiological responses and elemental accumulation strategies of two terrestrial orchids —
Gymnadenia conopsea and Dactylorhiza sambucina — growing on carbonate, ultramafic, and siliceous
substrates in the Central Balkans. Despite differences in phylogeny and ecology, both species showed
strikingly similar patterns of elemental partitioning. Macroelements (Ca, Mg, K, and P) consistently
accumulated in the above-ground organs, particularly in leaves and inflorescences, while most trace
elements (Cr, Co, Ni, Fe, and Mn) were retained in the roots, indicating an exclusion-based tolerance
strategy. However, D. sambucina exhibited a notable capacity for Zn and Cu accumulation in shoots,
suggesting species-specific flexibility in metal handling. Physiological analyses revealed that individuals
from carbonate soils exhibited the lowest stress levels, as indicated by higher photosynthetic pigment
concentrations, whereas plants from ultramafic sites showed elevated antioxidant activity and accumulation of phenolics and lipid peroxidation products, reflecting a stronger stress response. These findings demonstrate that exclusion remains the dominant metal tolerance mechanism in terrestrial orchids, but species-specific physiological adjustments and selective metal accumulation strategies contribute to their successful establishment on chemically contrasting substrates.Zarić N, Aničić Urošević M, editors. Book of Abstracts: The 3rd Conference of the International Association for Biomonitoring of Environmental Pollution: IABEP2025; 2025 Oct 13-15; Belgrade, Serbia. Belgrade: Institute of Physics; 2025. p. 104
The Influence of Adolescent Dietary Restriction on Memory Performance at 18 and 24 Months in Aged Wistar Rats
No full textDietary restriction (DR), defined as a 20–40% reduction in food intake without
malnutrition, impacts the organism depending on the age of onset and duration.
The developmental window from postnatal day (PND) 28 to PND 60 in rats—
spanning early through late adolescence—is a critical and highly sensitive period
for dietary interventions, as it coincides with ongoing maturation of prefrontal,
hippocampal and limbic systems that underlie adult social, emotional, and
cognitive behaviors. This study investigated the effects of 30% DR applied to
female Wistar rats during different adolescent phases: early (EADR, PND 28–35),
middle (MADR, PND 35–42), and early plus middle adolescence (EMADR, PND 28–
42), compared to ad libitum (AL) controls. Animals were tested at 18 and 24
months using the novel object recognition (NOR) task for recognition memory and
the Y maze spontaneous alternation test for spatial working memory. The NOR
test results showed that at 18 months old animals short-term memory was
preserved in the MADR and EMADR groups, while long-term memory was
preserved in the EADR and MADR groups. On the other hand, Y maze results
showed that EMADR preserved spatial working memory at both 18 and 24 months
of age, as these females spent more time in a new arm of Y maze, compared to AL
females of the same age. The effects of adolescent dietary restriction on memory
preservation at 18 and 24 months were assessed, demonstrating that early-life
caloric limitation preserves recognition and spatial memory in aged rats.Dragić M, editor. Book of abstracts: 9th Congress of Serbian Neuroscience Society; 2025 Oct 6-8; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2025
Pharmacological Challenge with D-Amphetamine reveals ADHD-related psychomotor activity in the A53T mouse model of Parkinson’s Disease
No full textThe Hualpha-Syn(A53T) transgenic mouse line G2-3 (JAX006823) is a model for
studying Parkinson’s disease (PD) and related synucleinopathies. Previous studies
have reported hyperlocomotion in this line, yet this feature of the model has often
been dismissed as an irrelevant artifact. However, hyperactivity in rodents may
reflect underlying neuropsychiatric traits, including those associated with
psychosis or attention-deficit/hyperactivity disorder (ADHD), which can be
distinguished using D-amphetamine challenge test. The aim of this study was to
assess, using D-amphetamine challenge, whether the observed hyperactivity in
the JAX006823 strain reflects an ADHD-like hyperactivity. The sample consisted
of 22 6-month-old male transgenic carriers, 23 of their non transgenic littermates
and 22 C57BL/6J mice (strain used in backcrossing for the colony maintenance).
Spontaneous activity in an inescapable open arena was evaluated for 30 minutes,
after which animals were injected with D-amphetamine (0.25 mg/kg, 2 mg/kg) or
saline and their behavior was monitored for an additional 120 minutes. The
increased locomotor response to novelty was observed as an endophenotypic
trait of the strain. Additionally, an inverse association between severity of
hyperactivity and the degree of calming effects of D-amphetamine (rate
dependency) was observed in mice of the JAX006823 strain. This study
characterized the observed behavior in the JAX006823 strain as ADHD related
psychomotor activity. The potential of using the D-amphetamine challenge in
distinguishing between different neuropsychiatric features underlying animal
behavior is further discussed, as well as the translational potential of the mouse
model considering that adult ADHD may be part of the PD prodrome.Dragić M, editor. Book of abstracts: 9th Congress of Serbian Neuroscience Society; 2025 Oct 6-8; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2025
Molecular responses to rehydration in resurrection fern Asplenium ceterach L.
No full textThe resurrection fern Asplenium ceterach L. (rustyback) exhibits remarkable desiccation tolerance, surviving extended periods of extreme dehydration and rapidly resuming metabolic activity upon rehydration. To elucidate the molecular mechanisms underlying this unique resilience, we conducted a comprehensive transcriptomics and specialized metabolomics analysis of dry, fresh and rehydrated (8h) fronds of rustyback fern. High-throughput RNA sequencing revealed dynamic regulation of gene expression associated with phenylpropanoid biosynthesis, plant hormone signal transduction, antioxidant defense, and osmoprotectant metabolism. Upon rehydration, a rapid reactivation of genes involved in photosynthetic machinery, and protein synthesis was observed, alongside transient induction of stress-responsive genes and signaling pathways linked to abscisic acid and reactive oxygen species. Thus, we have found that elevated expression of genes involved in the synthesis of phenylpropanoids and flavonoids is correlated directly with the accumulation of these specialized metabolites that function both as structural and signaling molecules. Together, our results show that during rehydration, a reprograming of the transcriptome occurs that defines the desiccation tolerance and resurrection behavior of rustyback fern.Book of abstracts: International Conference on Natural Sciences and Biotechnology: Kliment’s Days 2025: with satellite scientific conference: Reintroduction of Conservation: Reliant species; 2025 Nov 6-7; Sofia, Bulgaria. Sofia: The Faculty of Biology at Sofia University “St. Kliment Ohridski”; 2025. p. 171
Exploring the potential of underrated yet versatile crop Lunaria annua L.: New insights into honesty plant
No full textThe selected metabolite analysis and bioactive properties evaluation of edible plant L. annua seed extracts were assessed herein. The results indicate that seeds of L. annua have high energy value (406.6 kcal/100 g dw), with high share of carbohydrates (65.2 g/100 g dw), followed by proteins (26.47 g/100 g dw) and fat (4.46 g/100 g dw). Free sugar analysis showed presence of fructose, glucose and sucrose (0.77 g, 0.189 g and 3.85 g/100 g dw, respectively). Oxalic and malic acid were quantified < 1.0 g/100 g dw and fumaric acid only in trace. Monounsaturated fatty acids were predominant over polyunsaturated and saturated fatty acids (erucic, nervonic and oleic acid were dominant). The content of flavonoid compounds was several times higher than the content of phenolic acids (58.5 vs 9.4 mg/g). The methanol extract showed better potential as antioxidant agent than dichloromethane extract (EC50= 0.32 vs. 1.25 mg/mL, in TBARS test) and antibacterial activity in range of 0.50-2.00 mg/mL, with E. coli being the most susceptible to the activity of methanol extract (MIC 0.25 mg/mL, MBC 0.50 mg/mL). The other tested microorganisms showed quite uniform susceptibility to the extracts, but better than the positive controls E211 and E224. The tested samples demonstrated encouraging antifungal/anticandidal properties, and no cytotoxic effects onto spontaneously immortalized keratinocytes cell line HaCaT, indicating its safe application in terms of dermal exposure. Overall, results indicate that L. annua seeds may be considered as source of compounds used for the development of pharmacological agents with antioxidant and antimicrobial potential
Antiferroptotic effects of H2S donors against diabetic injury of β-cells in vivo and in vitro
No full textFerroptosis is a regulated non-apoptotic cell death
characterized by the increased lipid peroxidation
triggered by the accumulation of labile iron and
reactive oxygen species. The major antiferroptotic
signalling pathway is the GSH/GPX4/xCT axis, which is
controlled by the transcription factor Nrf2.
• The involvement of ferroptosis in diabetes-induced β-
cell injury was recently described by our team,
suggesting that it represents a potential target for
diabetes prevention and therapy.
• Originally considered a toxic gas, H₂S is now
recognised as a gasotransmitter and with its reactive
metabolites (persulfides, polysulfides and other
reactive sulphur species (RSS)) as important redox
signalling molecules.
• Recently, the antiferroptotic effect of H₂S and
related RSS has been demonstrated in various
pathologies. The antidiabetic role of H₂S has also
been demonstrated, although it remains unclear whether
it also reduces ferroptosis of β-cells.
• Here, we aimed to investigate the potential of H₂S/RSS
donors in preventing the development of diabetes,
focussing on their antiferroptotic effects.(poster) 22nd SFRRI Biennial Meeting 2025: The New Era of Redox Biology: from Basic Biochemistry to Redox Omics; 2025 Jun 3-6; Galway, Ireland