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
Assessment of Perfluoroalkyl Substances (PFAS) in MASLD Patients from Serbia: Insights from a Broader Multi-Omics Study
No full textPer- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with known bioaccumulative properties and increasing recognition for
their potential to disrupt metabolic pathways, including bile acid transport and lipid metabolism. Despite growing global attention, data on PFAS exposure
and distribution in the Balkan region, including Serbia, remain limited. This work presents preliminary findings on PFAS presence and explores potential
associations with bile acid metabolism in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and age-, BMI-, and sex-matched
controls, as part of a broader multi-omics investigation.
Plasma samples were collected from 122 participants (MASLD patients and matched controls) and metabolites were extracted using a monophasic solution
of methanol, methyl tert-butyl ether, and isopropanol (20:15:15) containing internal standards. Extracts were analyzed using ultra-high-performance liquid
chromatography coupled with quadrupole time-of-flight mass spectrometry on a C18 column. Data processing was performed using MZmine 3 software,
and compound annotation was based on an in-house spectral library.
Among the detected environmental contaminants, three PFAS compounds—perfluorohexane sulfonic acid (PFHxS) and both linear and branched isomers
of perfluorooctane sulfonic acid (PFOS)—were consistently identified across all samples, suggesting widespread low-level exposure in the cohort, with no
significant differences in PFAS abundance between MASLD patients and healthy controls.
These preliminary results highlight the presence of PFAS compounds in all participants, reflecting a baseline environmental exposure within this
population. Although no clear associations with MASLD status were observed, the integration of environmental contaminant data into multi-omics
frameworks is critical for uncovering subtle metabolic perturbations. Ongoing analyses will focus on profiling secondary bile acids and microbiota-derived
metabolites to explore potential downstream effects of PFAS exposure and their relevance to MASLD pathophysiology.Oral and Posterts Abstracts: 21st Annual Conference of the Metabolomics Society: Metabolomics2025; 2025 Jun 22-26; Prague, Czech Republic. Metabolomcis Society; 2025. p. 276
Impact of fermented foods consumption on gastrointestinal wellbeing in healthy adults: a systematic review and meta-analysis
No full textObjective: In recent years, the consumption of fermented foods (FFs) has been
linked with gastrointestinal health and wellbeing. Here, we systematically review
and meta-analyse the currently available evidence relating to this as part of
the COST Action PIMENTO and guided by the European Food Safety Authority
(EFSA) health claim dossiers.
Methods: MEDLINE, Scopus and Cochrane CENTRAL bibliographic libraries
were searched for relevant literature up to 31st January 2025. All eligible
studies were included for narrative review as per EFSA guidelines, but only
randomised controlled trials (RCTs) were considered for meta-analyses. Risk of
bias, mechanisms of action, bioactive compounds and safety were additionally discussed. Data was pooled using mean difference (MD)/standardized MD for continuous data and relative risk (RR) for dichotomous data. Certainty of evidence was evaluated through GRADE assessment.
Results: A total of 25 studies (19 RCTs included in meta-analysis) with 4,328 participants were included in the systematic review. Meta-analysis demonstrated the beneficial impact of FF consumption on frequency of bowel movements (MD 0.60, CI 0.04, 1.16, p = 0.04, I2 = 74%), stool consistency (Bristol Stool Form Scale) (MD 0.25, CI 0.03, 0.47, p = 0.03, I2 = 72%), gastrointestinal symptoms (SMD −0.60, CI −1.05, −0.15, p = 0.009, I2 = 90%) and intestinal transit time (−13.65 CI −21.88, −5.43, p = 0.001, I2 = 95%), among others. Certainty of evidence was highly variable and mostly low.
Conclusion: Our analysis suggests that FF consumption beneficially impacts the frequency of bowel movements, stool consistency, incidence of hard stools, intestinal transit time, abdominal symptoms, bloating, borborygmi, flatulence and degree of constipation.
Systematic review registration: This study was registered at the Open Science Framework (osf.io, registration number: q8yzd)
(Dys)regulation of the Immune System in Parkinson’s Disease: Methodologies, Techniques, and Key Findings from Human Studies
No full textParkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized
by the degeneration of dopaminergic neurons in the midbrain. While PD is typically considered a disorder
primarily affecting the central nervous system, there is mounting evidence of cellular dysfunction and PD
pathology occurring in the peripheral nervous system, likely preceding central manifestations. In this context, it has become increasingly evident that dysregulation of both the central and the peripheral immune system plays a key role in PD pathogenesis and progression. In this narrative review, we describe and discuss the methodological approaches employed in human studies to investigate immune responses in PD pathogenesis and progression, their main findings and the potential to unveil novel therapeutic avenues. In particular, we present methodologies employed in and insights gained from human genetic studies, techniques utilized to investigate neuroinflammatory processes in post-mortem and living human brains, to investigate the blood-brain barrier, as well as the involvement of peripheral T cells and innate immune cells. Additionally, we elucidate methodologies utilized to explore the roles of mitochondrial dysfunction and infectious diseases in PD. Finally, we address the causes behind conflicting findings in the published literature, which may stem from disparities in sample ascertainment schemes, immunological protocols, and analysis designs. Given these challenges, it becomes imperative to develop methodological guidelines to enhance the validity of immunological studies in PD and facilitate their translation into clinical medicine
Antibacterial effects of coniferyl alcohol-derived dehydrogenation polymer on chlamydial infection in vitro
No full textBackground: Chlamydia trachomatis, Gram-negative obligate intracellular bacteria, are a leading cause of sexually transmitted diseases worldwide, often causing severe complications. With no vaccine available and concerns about potential antibiotic resistance, the need for novel treatments is urgent. Dehydrogenation polymer of coniferyl alcohol in alginate hydrogel (DHP/Alg) has not yet been tested against chlamydial infections.
Material and Methods: The cytotoxicity of DHP/Alg on A2EN genital epithelial cells was assessed by measuring cell viability. To investigate its effects on Chlamydia-infected cells, we employed flow cytometry-based assays, fluorescence microscopy, and quantitative PCR (qPCR). Additionally, adhesion assays were performed to examine whether DHP/Alg interferes with Chlamydia entry into host cells.
Results: No cytotoxic effects of DHP/Alg in tested concentrations on A2EN cells were observed, confirming its safety. Infection and adhesion assays demonstrated a significant reduction in infection levels, suggesting that DHP/Alg directly targets Chlamydia elementary bodies, thereby disrupting their ability to adhere and initiate infection. Fluorescence microscopy revealed that 75 μg/mL DHP/Alg is the most effective dose evaluated to reduce chlamydial infection in vitro, as indicated by the decreased number of inclusions. These findings were further confirmed by qPCR analysis.
Conclusion: Our results suggest that DHP/Alg is a promising therapeutic option against chlamydial infections. The significant reduction in adhesion levels indicates that DHP/Alg effectively interferes with the initial stages of infection
Black raspberry seed oil – Chemical composition, antioxidant/antimicrobial activities and in vitro wound-healing potential
No full textThis study aimed to perform chemical characterization of black raspberry seed oil (Rubus occidentalis L., Rosaceae) from Serbia in terms of fatty acids and tocols composition, total carotenoid content, as well as to investigate its antioxidant/antimicrobial activities and in vitro wound-healing potential. GC/MS analysis revealed that linoleic (39.30 %), α-linolenic (30.49 %) and oleic (18.94 %) acid were dominant fatty acids. HPLC analysis highlighted γ-tocopherol as the prevailing tocopherol isomer (166.80 mg/100 g). Spectrophotometric method determined a total carotenoid content of 1.20 mg/100 g. Appreciable antiradical activity (DPPH – IC50 3.02 mg/mL; ABTS – IC50 1.33 mg/mL) and a high level of reducing ability (FRAP value of 393.74 μmol Fe2+/100 g) were observed. Significant antibacterial activity against Salmonella Typhimurium, Escherichia coli and Bacillus cereus, in addition to antifungal activity against strains from Aspergillus and Trichoderma genera, was demonstrated. By cell viability assay, no cytotoxicity (IC50 > 401 μg/mL) was established on human keratinocytes (HaCaT cells). The wound-healing activity, evaluated by scratch assay, was found to be 2.41-fold higher in HaCaT cells treated with 100 μg/mL of black raspberry seed oil (41.77 %) than in non-treated cells (17.34 %). Taken together, black raspberry seed oil holds promising health potential
Eriodictyol and Diosmetin Protective Potential in Skin Infection: Antimicrobial Action, Gene and Molecular Targets, and Keratinocyte Protection Against Bacteria-Induced Damage
No full textEriodictyol and diosmetin are bioactive flavonoids. This study explored their antimicrobial activities and antibiofilm potential along with the effect on pyocyanin and protease production and virulence-linked gene expression, followed by in silico molecular target predictions. Moreover, keratinocytes were used for the evaluation of cytotoxicity and protective antioxidant and anti-inflammatory effects in the infected cells. Both compounds have shown significant antibacterial capacity towards skin pathogens (minimal inhibitory concentrations 0.025–0.2 mg/mL). Their ability to prevent biofilm formation of Pseudomonas aeruginosa was drastic, as well as the impact on other virulence factors, proteases, and pyocyanin production. RT-qPCR determined downregulation of almost all genes examined (lasI, lasR, lasB, rhlI, rhlR, rhlC, pqsH, pqsR, pvdS, pvdF, phzM, and algK), while molecular docking predicted strong binding affinities to the LasI, LasR, PqsR, and QscR quorum-sensing proteins. Moreover, both compounds were not toxic to HaCaT and were able to reduce damage induced by P. aeruginosa in this cell line. Precisely, eriodictyol reduced levels of secreted IL-6 (from 335.32 to 261.76 pg), while both compounds reduced the formation of superoxide. Both eriodictyol and diosmetin displayed remarkable antimicrobial potential while employing a wide array of antimicrobial mechanisms, making them attractive candidates for further assessment and eventual incorporation into novel therapeutic strategies.This is the peer reviewed version of the following article: Carević Milićević, T., Novović, K., Stojković, D., Kostić, M., Kritsi, E., Zoumpoulakis, P. and Ivanov, M. (2025), Eriodictyol and Diosmetin Protective Potential in Skin Infection: Antimicrobial Action, Gene and Molecular Targets, and Keratinocyte Protection Against Bacteria-Induced Damage. Archiv der Pharmazie, 358: e70047
Transcriptomic and Clinical Profiling Reveals LGALS3 as a Prognostic Oncogene in Pancreatic Cancer
No full textBackground/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a β-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across tumor types remains incompletely understood. This study aimed to systematically investigate the transcriptomic impact of LGALS3 deletion and assess its clinical significance in cancer. Methods: We analyzed CRISPR-Cas9 knockout transcriptomic data from the SigCom LINCS database to characterize the consensus gene signature associated with LGALS3 loss using functional enrichment analyses. Pan-cancer survival analyses were conducted using TIMER2.0. Differential Gal-3 protein levels in ductal adenocarcinoma and normal pancreatic tissues were evaluated using the Human Protein Atlas. Finally, functional analyses were performed in pancreatic ductal adenocarcinoma (PDAC). Results: LGALS3 deletion across multiple cancer cell lines led to transcriptomic changes involving mitotic progression, stress responses, and axonal guidance pathways. High LGALS3 expression was significantly associated with worse overall survival in lower-grade glioma, PDAC, uveal melanoma, and kidney renal papillary cell carcinoma. LGALS3 knockout in YAPC cells recapitulated the pan-cancer findings, linking LGALS3 to cell morphogenesis and proliferation. Conclusions: These findings identify Galectin-3 as a key regulator of oncogenic programs and a potential prognostic biomarker in PDAC and other malignancies, with implications for therapeutic targeting
Two novel pyrimidine-artesunate hybrids overcome multidrug-resistance in non-small cell lung carcinoma through collateral sensitivity
No full textBackground: Two novel hybrid compounds (1 and 2) based on artemisinin and pyrimidine were tested for their
anticancer activity against non-small cell lung carcinoma (NSCLC), specifically targeting multidrug-resistance mediated
by P-glycoprotein (P-gp).
Materials and Methods: We used the human NSCLC cell line NCI-H460 (without P-gp expression), its multidrugresistant counterpart NCI-H460/R (with P-gp expression), and the normal human lung fibroblast cell line MRC-5. Cell
viability after treatment with 1 and 2, alone or in combination with the P-gp inhibitors dexverapamil (Dex-Ver) and
tariquidar (TQ), was assessed using the MTT assay. Accumulation of the rhodamine 123 (Rho 123), a P-gp substrate,
was analyzed by flow cytometry.
Results: Compounds 1 and 2 exhibited enhanced cytotoxicity towards resistant NCI-H460/R cells, indicating collateral
sensitivity. Both compounds also showed significant selectivity for cancer cells. Flow cytometry analysis revealed
that 1 and 2 effectively inhibited P-gp activity, as evidenced by the increased accumulation of Rho 123. Simultaneous
treatment of 1 and 2 with P-gp inhibitors indicated that the type of P-gp inhibition matters. The substrate inhibitor DexVer lowered cytotoxicity of 1 and 2, while the non-substrate inhibitor TQ, increased it. Flow cytometry also showed that
co-treatment with Dex-Ver further increased Rho 123 levels, indicating additive inhibition. However, when combined
with TQ, Rho 123 accumulation was comparable to that of TQ alone, suggesting that P-gp was already maximally
inhibited and the compounds made no further contribution.
Conclusions: The study demonstrates that pyrimidine-artesunate hybrids selectively target MDR cancer cells,
emphasising their potential to overcome drug resistance in cancer treatment.Čavić M, editor. Proceedings book: The 1st Regional SDIR-HDIR-MOKAD Congress; 2025 Oct 8-10; Belgrade, Serbia. Belgrade : Serbian Association for Cancer Research; 2025. p. 151. (Oncology Insights; No. 3)
Ecology and conservation status of Fritillaria montana in the special nature reserve Deliblato sands
No full textThe genus Fritillaria (Liliaceae) includes two species of significant ecological and
conservation value within the Special Nature Reserve Deliblato Sands: Fritillaria montana
Hoppe (syn. F. orientalis auct. non Adams) and Fritillaria meleagris L. According to national
conservation regulations, F. montana is classified as endangered. Although this species occurs
in various types of plant communities, in Deliblato Sands it has a very limited distribution,
growing mainly in lowland oak and linden forests, but also on the shaded sides of larger
shrubby stands. This study assessed the current population status, distribution, and ecological
characteristics of Fritillaria montana, and identified the primary threats to its survival. Field
investigations included population surveys, habitat characterisation, and threat assessment.
Results indicate fragmented and declining populations, primarily affected by habitat
succession, overgrazing, and anthropogenic disturbances. The findings highlight the urgent
need for active conservation measures, including habitat restoration, protection from grazing,
and continuous population monitoring. Preserving Fritillaria species within the Deliblato
Sands is essential for maintaining the ecological integrity and botanical diversity of this unique
sandy ecosystem.Golub D, editor. Book of asbtracts: V Symposium of biologists and ecologists of Republic of Srpska SBERS2025; 2025 Nov 13-25; Banja Luka, Bosnia and Herzegovina. Banja Luka: Faculty of Natural Sciences and Mathematics, University of Banja Luka; 2025. p. 147
Distribution, scale, and drivers of mass mortality events in Europe's freshwater bivalves
No full textMass mortality events (MMEs) are decimating populations and compromising key ecosystem functions around the globe. One taxon particularly vulnerable to MMEs is freshwater bivalve mollusks. This group has important ecosystem engineering capacities and includes highly threatened and highly invasive taxa. Thus, MMEs of freshwater bivalves have important implications for conservation and ecosystems. Despite this, little is known about the magnitude, frequency, duration, distribution, and causes of freshwater bivalve MMEs. Using a questionnaire, we compiled data from 239 reports describing freshwater bivalve MMEs across 22 European countries since 1960. With these data, we analyzed trends in MME timing, location, and magnitude; identified the species affected; and evaluated the suggested causes (including reporter certainty). We found that the frequency of reports of MMEs increased each year, MMEs affected a broad range of species, clear geographical patterns linking certain causes to specific locations were lacking, factors related to drying and habitat destruction predominated suggested causes, and considerable uncertainty surrounded the causes of many MMEs, particularly those associated with potential pollutants and disease agents. Based on our findings, we recommend the standardization of many aspects of MME research (e.g., reporting and recovery assessment protocols), increased surveying for MMEs, further investigation into the causes of MMEs, especially those with significant uncertainty, and immediate actions to improve waterbody management, mitigate the effects of high temperatures, and further protect freshwater bivalves through the development and implementation of appropriate management actions and legislation