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Antidiabetic potential of Gentiana dinarica root extracts and their active component norswertianin and its glycoside norswertianin-1-O-primeveroside
No full textXanthones, the main secondary metabolites found in Gentiana dinarica, display various biological activities.
In in vitro cultured and particularly in genetically transformed G. dinarica roots, there is a higher
content of xanthones. The aim of this study was to investigate and compare antidiabetic properties of
secondary metabolites prepared from G. dinarica roots collected from nature, cultured in vitro or genetically
transformed. We compare HPLC secondary metabolite profiles and the content of the main extract
compounds of G. dinarica methanol root extracts with their ability to scavenge DPPH free radicals and
inhibit intestinal α-glucosidase and α-amilase in vitro. Anti-hyperglycemic activity of extracts was tested
further in vitro by glucose uptake test and in vivo on glucose-loaded Wistar rats. Our findings reveal that
the most prominent radical scavenging potential and potential to control the rise in glucose level, detected
in xanthone-rich extracts, were in direct correlation with an accumulation of xanthones norswertianin
and norswertianin-1-O-primeveroside in roots cultured in vitro and genetically transformed.Robajac D, editor. Book of abstracts: FEBS3+ meeting: Advances in Molecular Biosciences: From Genes to Personalized Therapies; 025 Sep 24-27; Belgrade, Serbia. Belgrade: Faculty of Chemistry, Serbian Biochemical Society; 2025. p. 159
Bioactive compounds in fermented foods: a systematic narrative review
No full textThis systematic narrative review aims to catalogue bioactive compounds that
are formed during the fermentation process and identified as contributors to
positive health outcomes in human clinical studies where fermented foods were
used as dietary interventions. Under “The European Cooperation in Science and
Technology” (COST) Action CA20128 – “Promoting Innovation of Fermented Foods”
PIMENTO framework, a systematic literature search was conducted across PubMed,
Scopus, and the Cochrane Library. The search initially identified 2,411 studies, of
which 50 met the predefined inclusion criteria. In all included studies, fermented
foods were used as nutritional interventions, and the bioactive compounds they
contained were either hypothesised or directly analysed in relation to statistically
significant health effects observed in humans. Findings were summarised in
“Population, Intervention, Comparator, Outcome” (PICO)-structured tables and
classified by health domain. The reported effects were grouped under the following
categories: cardiovascular health, lipid metabolism, glucose regulation, immune
modulation, neuroprotection, liver function, and other health outcomes. Across
the included studies, a total of 31 bioactive compounds and/or compound groups
were identified in fermented foods, including bioactive peptides, polyphenols
(epicatechin, genistein), γ-aminobutyric acid (GABA), acetic acid, curcumin, and
arabinoxylans. The mechanisms of action associated with these compounds were
explored in the non-systematic section of the review, supported by findings from
in vitro, animal and human studies. By linking individual bioactive compounds
derived from fermented foods to clinical outcomes and underlying mechanisms,
this review provides a comprehensive and functional resource for nutritional
science, fermented food innovation, and public health applications
A systematic review of prospective evidence linking non-alcoholic fermented food consumption with lower mortality risk
No full textFermented foods are consumed worldwide and are increasingly being studied for their potential health benefits. Although their consumption is widespread, their association with long-term health outcomes such as mortality risk remains unclear. The aim of this systematic review was to assess the association between the consumption of fermented foods and risk of all- cause, cardiovascular, and cancer-related mortality in generally healthy adult populations in accordance with the European Food Safety Authority (EFSA) framework for the substantiation of health claims. A comprehensive literature search identified prospective cohort studies from 1970 to 2025 that investigated the association between fermented food consumption and mortality outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale, and strength of evidence was evaluated based on study quality, sample size, and precision within a structured narrative framework that also classified the direction of association across categories. A complementary non-systematic review examined the compositional characteristics, mechanisms of action, and potential health risks associated with fermented foods. Fifty-two cohort studies were included. Fermented milk products (including yogurt), chocolate, and fermented soy products (particularly natto) suggested a modest inverse association with all-cause and cardiovascular mortality. Cheese was associated with reduced all-cause mortality in some studies, but it showed inconsistent effect on cardiovascular mortality. The evidence for cancer-related mortality was weaker, although yogurt and fermented milk displayed some protective trends. Evidence from a single cohort suggested a potential reduction in all-cause mortality with fermented vegetable consumption, whereas fermented meat suggested no clear association with mortality. Biological plausibility was supported by fermentation-derived compounds such as bioactive peptides, polyphenols, isoflavones, natto-kinase, and vitamin K2. Habitual consumption of certain fermented foods may be associated with modest reductions in mortality risk, but the current evidence remains insufficient to support EFSA-approved health claims. Randomized controlled trials are essential to demonstrate causality. While long-term trials with mortality endpoints are not feasible, studies targeting intermediate outcomes linked to mortality offer a practical alternative. These should be complemented by observational studies to capture long-term, real-world associations. Together, such efforts support the objectives of the COST Action PIMENTO (CA20128) in building a more robust evidence base on fermented foods and health
The mechanism of action of HYCO-3, an Nrf2 activator/CO releaser hybrid in inhibiting autoimmune disease development in mouse models
No full textThe novel hybrid compound HYCO-3, consisting of a CO-releasing molecule conjugated to a fumaric
ester derivative, is known to release CO and simultaneously induce Nrf2-dependent expression of the
CO-producing enzyme HO-1. We have previously shown that HYCO-3 ameliorates EAE, the animal model of multiple sclerosis1. The immunomodulatory potential of HYCO-3 was tested on myeloid-derived
cells, microglial cells and T lymphocytes obtained from EAE-immunized mice. HYCO-3 exerted immunomodulatory effects on all the examined cell populations by inhibiting the generation of pro-inflammatory cytokines and NO, and downregulated antigen-presenting capacity of these cells2.
In the animal model of type 1 diabetes, HYCO-3 inhibited the development of the disease by halting
infiltration of immune cells in the pancreas and maintaining normoglycaemia. HYCO-3 decreased the
frequency of IL-17+CD8+ cells in the pancreatic draining lymph nodes and IL-17+CD4+ cells in the pancreas, which are key pathogenic populations in disease progression. Also, HYCO-3 increased the frequency of Treg cells, displaying a shift towards the protective Treg axis. Furthermore, we determined
the kinetics of activation of Nrf-2 and CO levels in blood, pancreas, spleen and liver during oral application, thus correlating the effect of HYCO-3 with its mechanism of action.Robajac D, editor. Book of abstracts: FEBS3+ meeting: Advances in molecular biosciences: from genes to personalized therapies; 2025 Sep 24-27; Belgrade, Serbia. Belgrade: Serbian Biochemical Society; Faculty of Chemistry, University; 2025. p. 70-1
Untargeted UHPLC-QToF profiling of bee-collected pollen originating from Amorpha fruticosa L. plant
No full textAmorpha fruticosa L. (known aslo as false indigo-bush) is melliferous plant known as a good source of both pollen and nectar for honeybees. Although it is invasive species it is recognized as important part of apiflora in Serbia [1]. Therefore, the aim of this research was to collect pollen from hive’s traps (further labeled as bee-collected pollen, BCP), originating from A. fruticosa plants, and to examine content of different plant secondary metabolites presented in BCP. Extraction procedure was as follow- BCP was mixed with 80% methanol (1:10, m/v) and extraction of phytochemicals was lasted for 3 hours in tube protected from the light to obtained free (extractable) fraction. After that, sample was digested in alkaline condition to liberate bound fraction of phytochemicals as it is described in our previous research [2].The obtained supernatants were separated from solid residues by centrifugation (4000 g) and it was placed in tube protected from the light in the refrigerator (4°C) before further processing. Sample was prepared for HPLC - QToF-MS/MS analysis by following procedure described in our previous research [2]. Based on the obtained phytochemical profiles, in total, 39 phenolics, 22 identified and 4 unidentified phenylamides, 4 anthocyanins (petunidin derivatives) and 2 organic acids were identified in both fractions. However, extractable fractions was characterized with significantly higher diversity of the observed phenolic compounds including 22 flavonols/derivatives, 8 phenolic acids/derivatives, 3 flavone/flavanone, 4 petunidin derivatives, and both oganic acids (malic and citric). Also, it was characterized with presence of all (un)identified phenyl amides (including 15 putrescine, 6 spermidine, 1 spermine derivatives, and 4 unidentified compounds). On the contrary, bound fraction contained 15 phenolics, and only 5 phenyl amides and one petunidin derivative (petunidin 3-O-(6"-hexosyl)hexoside) as well as citric acid. BCP obtained from A. fruticosa L. can be good source of different phytochemicals with expressed bioactivity applicable in human nutrition and medicine.Tosti T, Dapčević A, Tešić Ž, editors. Book of abstrcats: 29th International Symposium on Separation Sciences: ISSS 2025; 2025 Sep 25-27; Belgrade, Serbia. Belgrade: Serbian Chemical Society; 2025. p. 116
List of 133 references narrowly focused on secondary somatic embryogenesis (SSE) in plants, with abstract, year of publication and DOI, downloaded from Scopus
No full textThis dataset is a product of the research funded by the Ministry of Science, Technological Development and Innovation, Republic of Serbia (University of Belgrade, Institute for Biological Research "Siniša Stanković"). The dataset includes the list of 133 references narrowly focused on secondary somatic embryogenesis (SSE) in plants, with abstract, year of publication and DOI, downloaded from Scopus, from years 1983 to 2024
Interaction studies of biliverdin-Cu complex formation using XANES, XRF, and DFT analyses and its effect on cytotoxicity in glioblastoma cell line (U251)
No full textCu2+ and biliverdin build complex (BV–Cu) that is stable in water at physiological pH and may develop in living systems. However, the interactions of BV-Cu with cells and even its structure are not fully understood. Herein we showed that BV-Cu complex was significantly more cytotoxic to a human cell line than equimolar Cu2+ and biliverdin. Micro-XRF-generated maps of elements showed that in contrast to Cu2+-treated cells which exhibited physiological compartmentalization of Cu, cells treated with BV-Cu had almost even distribution of Cu throughout the cytosol. XANES showed that the complex contains Cu1+ with distorted tetrahedral or square planar geometry. This implicates that the formation of the complex includes redox reaction between the metal ion and the ligand. As a result, the complex is nominally made of Cu1+ and BV radical cation. The redistribution of charge and spin densities between Cu2+ and tetrapyrrole ring during complex formation was also corroborated by DFT modelling. Cells exposed to BV-Cu were loaded with Cu that remained in 1+ form with altered local geometry than the complex. The cytotoxicity of the BV-Cu complex may come as a result of its interference with regular Cu transport and storage routes
De Novo Transcriptome Assembly of Nepeta nuda L. leaf trichomes
No full textAssembled transcriptome from paired-end RNA sequencing of Nepeta nuda L. leaf trichomes using Illumina NovaSeq 6000, in FASTA format. The transcripts/unigens had a mean GC content of 41.58%, an average contig length of 564.47 bp, a median contig length of 316.0 bp, and an N50 of 798 bp. Nepeta nuda transcriptome data are a part of phyloNEPETOME data platform
Comparative Study of Ion Channels in Filamentous Fungi Following the Novel Development of Laser Nanosurgery for Cell Wall Removal
No full textThe patch-clamp technique has been a standard method for the functional characterization of ion channels in living cells for several decades. However, despite the fungal kingdom's vast diversity and significance, the study of ion channels in filamentous fungi remains very limited due to the difficulty of electrically isolating membrane patches by creating a GΩ seal with a glass pipette. Cytoplasmic droplets (CDs) are a model system used in our research group that has so far yielded the most data on novel channels in the native membrane, but this approach is limited to the use of giant sporangiophores of P. blakesleeanus. CDs have been shown to be metabolically active, enclosed by a plasma membrane, and to contain many nuclei, making them suitable for studying membrane channels in their native physiological state [1]. The development of laser nanosurgery for precise cell wall removal enabled the first ion current recordings from P. blakesleeanus mycelium [2]. Results show differences in dominant activities compared to sporangiophore membrane, as well as the spatial distribution of distinct single ion channel activities along the hyphae. The osmotically sensitive, outwardly rectifying inactivating current (ORIC)—the dominant current of the CD membrane and the most thoroughly studied to date [3]—is absent in recordings from both the whole protoplast membrane and excised membrane regions, suggesting that its expression may be sporangiophore-specific. A dominant current in the protoplast membrane seen in all whole-protoplast recordings is an inward inactivating anionic current that resembles a rarely observed activity in CDs, that remains to be fully characterized. Various single channel activities were recorded under the same recording conditions on both CDs and mycelium protoplast in parallel. Besides ORIC, a 70 pS potassium current- one of the first single-channel currents described in the CD membrane [4]- has also not been observed in the mycelium membrane, while several activities suggest a novel type of ion channels specific for the mycelium. The greatest advantage of using laser nanosurgery to obtain mycelial protoplasts is that the method can be further optimized for a wide range of filamentous fungi species. One ongoing project is focused on adjusting the protocol for phytopathogenic fungal species, to be followed by measurements of the currents induced by the insertion of peptides from biocontrol species of the genus Trichoderma. We have recently studied their effects on the growth inhibition of autochthonous phytopathogens [5], and it was further observed that peptaibol-containing extracts of T. harzianum exert an acute lethal effect on microscopic specimens of R. solani when applied extracellularly. Overall, this strategy represents a significant step toward accelerating the discovery of novel ion channels and enabling the systematic exploration of their diversity and physiological roles in filamentous fungi.Rabasović M, Ralević U, Lekić M, Krmpot A, editors. Abstracts of tutorial, keynote, invited lectures, progress reports and contributed papers: X International School and Conference on Photonics PHOTONICA 2025; 2025 Aug 25-29; Belgrade, Serbia. Belgrade: Institute of Physics; 2025. p. 43
Antimelanoma effect of mefloquine-mediated lysosomal destabilization and glucose deprivation in A375 melanoma cells
No full textBackground: Tumor cells often exhibit enlarged lysosomes and a high reliance on glycolysis for energy production,
distinguishing them from normal cells. These features support their rapid proliferation and survival under stress.
Enlarged lysosomes are more prone to membrane destabilization, while glycolytic dependence renders tumor cells
vulnerable to metabolic disruption. Targeting these distinct traits with lysosome-disrupting agents and glucose
deprivation offers a promising therapeutic strategy. To test this theory, we exposed A375 melanoma cell line and normal human dermal fibroblasts (NHDF) to mefloquine, a lysosomotropic disruptive agent, in glucose-free medium.
Material and Methods: Cell viability upon treatments was determined by crystal violet and MTT tests, and meflouqine
concentrations with the most pronounced anti-melanoma effects in combined treatment were selected for further
investigation. The type of cell death (apoptosis, necrosis) was determined using Annexin V/PI flow cytometry and
changes in lysosomal acidification were determined by flow cytometry and fluorescent microscopy after staining with
Lysotracker red.
Results: Mefloquine reduced A375 cell viability in a dose-dependent manner and glucose depletion led to proliferation
arrest, with their combination demonstrating higher cytotoxicity. The effect was absent in treated NHDF cells. Apoptosis
was induced by both agents, as demonstrated by Annexin V/PI flow cytometry, and was significantly intensified when
the agents were applied in combination. Furthermore, Lysotracker red staining revealed that lysosomal acidification
decreased following the combined treatment, in contrast to the increase observed with each treatment individually.
Conclusions: Combined treatment with mefloquine and glucose deprivation elicited a potent proapoptotic response in
A375 melanoma cells, while sparing NHDF cells, indicating that this dual-targeting approach may serve as a promising
therapeutic strategy for melanoma.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. 159-60. (Oncology Insights; No. 3)