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Oral administration of the probiotic strain Lactobacillus helveticus BGRA43 reduces high-fat diet–induced hepatic steatosis in mice and restores gut microbiota composition
No full textIntroduction: The prevalence of metabolic dysfunction-associated steatotic liver
disease (MASLD) is rapidly increasing. Modulation of the gut microbiota through
the use of probiotics has been recognized as an important option for the
treatment of hepatic steatosis. Previous studies suggested that the bacterial
strain Lactobacillus helveticus BGRA43 (LHBGRA43) can reduce inflammation
and improve the bacterial balance in the gut. The aim of this study was to
investigate whether oral administration of LHBGRA43 in mice fed a high-fat
diet contributes to the reduction of hepatic steatosis through its beneficial effects
on the composition of the gut microbiota.
Methods: Male C57BL/6J mice (2.5 months old) were divided into three groups: a
control group fed a standard diet (10% kcal fat), a high-fat diet (HFD) group (60%
kcal fat for 14 weeks) and a HFD group that received freeze-dried LHBGRA43
dissolved in PBS orally for the last 5 weeks of the diet.
Results: Histological analysis of the liver showed that animals fed HFD exhibited
hepatic steatosis, while no lipid droplets were present in the liver of animals
receiving LHBGRA43. This decrease in steatosis correlated with decreased level
of sterol regulatory element-binding protein-1c, reduced expression of the fatty
acid transporter Cd36, enzymes involved in ceramide synthesis and
proinflammatory markers. The administration of LHBGRA43 also improved the
integrity of the small intestine barrier, as evidenced by an increased level of ZO-1
protein. The observed reduction in intestinal permeability was associated with a
decreased Firmicutes/Bacteroidota ratio and increased abundance of the genera
Alistipes, Acetatifactor and Odoribacter, as well as a decreased concentration of
branched-chain 4-methylvaleric acids.
Discussion: In conclusion, the restoration of the gut microbiota composition in
combination with the strengthening of the small intestine barrier suggests that
LHBGRA43 could be used as a general probiotic strain with ameliorative effects on
hepatic lipid accumulation and lipotoxicity
Developing under artificial light is not so bright: Oxidative stress as a physiological response to light pollution across amphibian life stages
No full textLight pollution has emerged as a new environmental challenge. Natural light has long been a selecting force in shaping physiological, morphological and behavioral traits across species. The introduction of artificial light at night (ALAN) disrupts the natural light-dark cycle, affecting a broad range of biological processes. In amphibians, ALAN has been suggested as a potential driver behind demographic declines in recent years. In this study, we investigated how exposure to cold LED light affects the development, body length, and oxidative status of the European tree frog (Hyla arborea). Individuals were exposed to ALAN from egg hatching (GS25) to two developmental endpoints: the larvae (GS38) and the juveniles. The experiment included three night-time light conditions: a natural dark control (<0.3 lx), LED light intensity at 20 lx, and LED light intensity at 90 lx. Larvae reared under artificial light reached metamorphosis in a shorter period and exhibited larger body sizes. Nocturnal light also induced changes in oxidative status across life stages. Tadpoles under both 20 lx and 90 lx levels experienced greater oxidative damage of lipids. Likewise, juveniles had higher oxidative damage of proteins and elevated activities of the first-line antioxidant defense enzymes (SOD, CAT and GSH-Px) in response to both light intensities. Our results show that exposure to ALAN shapes development and body size of amphibians, which appears to be accompanied by disturbances in redox balance. Overall, we highlight that ALAN can be a factor affecting amphibian populations, and thus it should be taken into consideration in future conservation strategies
Naturally aged rats, characterized by persulfidation decline, provide an adequate translational preclinical model for BPH: A hypothesis
No full textBenign prostatic hyperplasia (BPH) is a prevalent age-related disorder characterized by progressive prostate enlargement. Current preclinical models fail to replicate decline in persulfidation and chronic oxidative stress, inflammation, and cellular aging that drive human BPH pathology. We propose that a naturally aging rat model (middle to early old-aged) provides a superior alternative by mimicking BPH progression as a multifactorial aging-associated disease. Furthermore, we hypothesize that a decline in persulfidation (PSSH) may be a novel biomarker for oxidative stress susceptibility, allowing precision medicine approaches in BPH treatment. Naturally, aging models likely provide a more translationally relevant platform for preclinical drug testing, leading to improved therapeutic validation and regulatory approval. We propose multicenter validation of persulfidation biomarkers, integration into clinical trials, and their application in biomarker-guided BPH therapy. This hypothesis shifts BPH research towards a multi-dimensional aging-based disease model, facilitating biomarker-driven precision medicine strategies that could significantly improve treatment outcomes.This is the peer reviewed version of the following article: Miler M, Mijajlović V, Vukojević M, Mojić M, Filipović B, Živanović J, Ajdžanović V. Naturally aged rats, characterized by persulfidation decline, provide an adequate translational preclinical model for BPH: A hypothesis. in Medical Hypotheses. 2025;206:111844. [https://doi.org/10.1016/j.mehy.2025.111844
Under-explored Asteraceae plants as a valuable source of bioactive compounds with enzyme inhibitory activity
No full textNatural resources of bioactive compounds with enzyme inhibitory activity from plants which belong to
Asteraceae family are under-explored. The main goal of this research was to determine the chemical
profile of Asteraceae plants extracts and ability to inhibit the activity of enzymes. Teen different plants
were investigated: Solidago virgaurea, Tanacetum vulgare, Tussilago farfara, Cota tinctoria, Inula
ensifolia, Eupatorium cannabinum, Cichorium intybus, Tanacetum parthenium, Tragopogon pratensis,
and Cichorium endivia. All plants belong to the Asteraceae family and nine different genera (two plant
varieties were researched within genus Tanacetum). Conventional maceration with 60% ethanol, 1:20
m/v solid/liquid ratio, at room temperature, for 24 h and with constant shaking (180 rpm) was performed
for obtaining the Asteraceae plant extracts. Extracts inhibitory activity was investigated against four
enzymes: α-amylase, α-glucosidase, acetylcholinesterase, and tyrosinase. Chemical profile of plant
extracts was defined by LC-MS. Tanacetum vulgare expressed the highest ability to inhibit α-amylase
(317.23 μM ACAE/g), while Eupatorium cannabinum showed the lowest inhibitory activity (188.60 μM
ACAE/g). In term of ability to inhibit the α-glucosidase, Solidago virgaurea (245.12 μM ACAE/g)
possessed the highest value and Tragopogon pratensis (102.79 μM ACAE/g) the lowest. For enzyme
inhibitory activity against acetylcholinesterase Solidago virgaurea (0.12 μM GALAE/g) had significantly
high inhibitory potential in comparison to the other plants. By analyzing the enzyme inhibitory activity
against tyrosinase, Inula ensifolia (203.52 μM KAE/g) stood out as the best. According to LC-MS
analysis 130 compounds were identified and quinic, fumaric, dihydroxybenzoic, quercetin 3-O-hexoside,
kaempferol 3-O-hexoside, luteolin, quercetin, apigenin and kaempferol were present in Solidago
virgaurea, Tanacetum vulgare, Tussilago farfara, Cota tinctoria and Inula ensifolia. Exploring and
implementing less-known Asteraceae plants rich in bioactive compounds with enzyme inhibitory activity
in form of functional food or dietary supplements may fight with today's global diseases such as
Alzheimer diseases, diabetes type two and skin pigmentation.Popović-Đorđević J, Kostić A, editors. Book of Abstracts: 3rd European Symposium on Phytochemicals in Medicine and Food (3-EuSPMF); 2025 Jul 1-4; Belgrade, Serbia. Belgrade: University of Belgrade, Faculty of Agriculture; 2025. p. 90
Liraglutide and strength-endurance training as modulators of the stress axis in middle-aged female rats
No full textThe pituitary-adrenal (PA) axis undergoes structural and functional changes with aging, including elevated glucocorticoid levels, impaired negative feedback, and reduced stress responsiveness. These alterations contribute to endocrine imbalance and adverse health outcomes, highlighting the importance of interventions that support endocrine health during aging. Liraglutide, a GLP-1 receptor agonist, exerts endocrine-modulating effects beyond its established roles in glycemic and weight control, while exercise supports endocrine health by promoting PA axis function. Although both liraglutide and exercise show potential in modulating the PA axis, data on their effects in aged animals remain limited. To address this gap, we investigated the individual and combined effects of liraglutide and strengthendurance training in 16-month-old female Wistar rats, using histomorphometric, molecular, and hormonal analyses of pituitary and adrenal glands. Animals were divided into four groups: control (C, 0.3 ml/day saline subcutaneously), liraglutide (L, 0.3ml/day Saxenda® (0.186 mg/kg/day) subcutaneously), strength- endurance training (E, ladder-climbing, 25-50% body weight load, 3 times/week) and liraglutide + strength-endurance training (L+E). The treatment lasted seven weeks, preceded by a two-week adaptation period. Pituitary Pomc expression and plasma ACTH levels were elevated in E group (p<0.05 vs.C), without changes in pituitary weight. Adrenal weight, adrenal volume, and zona fasciculata volume were reduced in L group (p<0.05 vs.C, for all). Mc2r expression was downregulated in L (p<0.05 vs.C) and L+E (p<0.05 vs.C), along with downregulation of Cyp11b1 expression in L (p<0.01 vs.C) and L+E (p<0.05 vs.C) groups. These molecular changes were accompanied by lower plasma corticosterone levels in L (p<0.05 vs.C) and L+E (p<0.001 vs.C) groups. Volume density of blood vessels within the adrenal cortex was reduced in L (p<0.05 vs.C) and L+E (p<0.01 vs.C) groups, suggesting microvascular remodeling associated with suppressed steroidogenesis. Liraglutide alone induced pronounced structural changes in the adrenal gland, and suppressed adrenal steroidogenesis, both administered alone and combined with strength-endurance training. In contrast, strength-endurance training alone enhanced pituitary activity without altering adrenal morphology. These findings suggest that liraglutide and strength-endurance training modulate the PA axis at both structural and functional levels in middle-aged female rats.Meeting Abstract Book: 12th ESE Young Endocrinologists and Scientists (EYES); 2025 Sep 26-28; Milan, Italy. Oxford: University Press; 2025. p. i31-2. (European Journal of Endocrinology; Vol. 193; Suppl. 1)
Vitamins formed by microorganisms in fermented foods: effects on human vitamin status—a systematic narrative review
No full textIntroduction: Vitamin deficiencies remain a global health issue, particularly
among vulnerable populations. As microorganisms also produce vitamins, this
has led to considering Fermented Foods (FF) as potential vehicles for improving
vitamin intake. This systematic narrative review, which exclusively relies on
human studies, aims to assess the extent to which the consumption of vitaminrich
FF contributes to the maintenance or enhancement of vitamin status in
healthy or deficient populations.
Methods: A comprehensive literature search (1970–2024) was conducted
following the protocols of EFSA and the COST Action PIMENTO to identify
interventional and observational studies investigating the influence of FF on
biomarkers of vitamin status.
Results: Findings confirm that certain microorganisms, including Bacillus subtilis,
Propionibacterium freudenreichii, and some lactic acid bacteria, can increase
the levels of vitamins K2, B2, B9, and B12 in FF. Evidence of bioavailability and
physiological effects is reported. Notably, folate (vitamin B9) bioavailability was
enhanced in some cases following the consumption of Camembert cheese naturally rich in folate, while vitamin K2 status was effectively improved in several studies on natto (fermented soy) and in one study on Jarlsberg cheese. However, evidence for other B vitamins (B1, B2, B3, B5, B6 and B12) is limited or inconsistent, and no human evidence exists for other vitamins. Vitamin bioavailability was found to be significantly influenced by the food matrix, fermentation type, microbial strain, and the form of the vitamin (vitamers). Effects may also be influenced by interactions with gut microbiota, including microbial vitamin synthesis and modulation of absorption.
Discussion: Despite encouraging data, there is a lack of well-controlled, large-scale human studies to validate FF as a sustainable strategy to improve vitamin status. Future human studies research should investigate strain-specific effects, food matrix interactions, and long-term health outcomes
Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group
No full textIn the past decade, precise targeting through genome editing has emerged as a promising alternative to traditional therapeutic approaches. Genome editing can be performed using various platforms, where programmable DNA nucleases create permanent genetic changes at specific genomic locations due to their ability to recognize precise DNA sequences. Clinical application of this technology requires the delivery of the editing reagents to transplantable cells ex vivo or to tissues and organs for in vivo approaches, often representing a barrier to achieving the desired editing efficiency and safety. In this review, authored by members of the GenE-HumDi European Cooperation in Science and Technology (COST) Action, we described the plethora of delivery systems available for genome-editing components, including viral and non-viral systems, highlighting their advantages, limitations, and potential application in a clinical setting
Adamantane–sclareol hybrids selectively target multidrug resistant glioblastoma cells by inducing oxidative stress
No full textBackground: Glioblastoma is an aggressive brain malignancy characterized by a limited therapeutic response, primarily
due to multidrug resistance (MDR). One critical contributor to MDR is the activity of P-glycoprotein (P-gp), an efflux
transporter that decreases drug accumulation within cells. Inhibiting P-gp and disrupting redox homeostasis may
present viable strategies to counteract MDR. This study evaluates the in vitro biological activity of two adamantanesclareol hybrid compounds (1 and 2) in terms of glioblastoma cell viability, P-gp functionality, and oxidative stress.
Materials and Methods: Our experimental model comprises the human glioblastoma U87 cell line (P-gp-negative), its
drug-resistant counterpart U87-TxR (P-gp-positive), and normal human astroglial SVG p12 cells. Cytotoxicity assays for
compounds 1 and 2, alone or in combination with paclitaxel (PTX), were conducted via the MTT. Flow cytometry was
employed to assess P-gp activity, apoptosis induction, and intracellular reactive oxygen species (ROS) levels. Real-time
PCR was performed to quantify the expression of antioxidant-related genes.
Results: Compounds 1 and 2 exhibited a more pronounced growth inhibition in glioblastoma cells compared to normal
SVG p12 cells. These hybrids bypassed MDR in glioblastoma cells, illustrated by lower IC50 values in MDR U87-TxR cells
relative to sensitive U87 cells. Apoptosis rates were significantly higher in U87-TxR cells when treated with the hybrids
compared to U87 cells. Furthermore, both compounds enhanced the intracellular accumulation of the P-gp substrate,
rhodamine 123, indicating their P-gp inhibitory effects. The combination of PTX with compounds 1 and 2 demonstrated
predominantly synergistic interactions. Notably, both hybrids increased intracellular ROS levels, especially in U87-TxR
cells. This oxidative stress response was also followed by upregulation of antioxidant-related genes in both glioblastoma
lines.
Conclusions: The adamantane-sclareol hybrids exhibit selective cytotoxicity against glioblastoma cells, with a marked
effect on MDR glioblastoma cells, as confirmed by MTT assay. This selective cytotoxicity was also confirmed by enhanced
apoptosis induction and disruption of the redox balance, indicating a phenomenon known as collateral sensitivity.
Additionally, both hybrids inhibited P-gp activity and displayed synergistic interactions with PTX, underscoring their
therapeutic potential in the treatment of glioblastoma.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. 144. (Oncology Insights; No. 3)
Relict species the Pulsatilla montana in the deliblato sands: conservation challenges and pharmacological perspectives
No full textThe genus Pulsatilla (Ranunculaceae) comprises relict and endemic species that inhabit dry
grasslands and sandy habitats across Eurasia. Within the Special Nature Reserve Deliblato
Sands (Serbia), significant populations of Pulsatilla montana represent important components
of local biodiversity but are exposed to increasing environmental pressures. The species is
listed as Strictly Protected under Serbian national legislation, highlighting its conservation
significance. This study aimed to assess the population status of P. montana, identify key
threats to its survival, and conduct a preliminary phytochemical analysis to evaluate its
pharmacological potential. Fieldwork included population mapping, abundance estimation,
and habitat characterization, while laboratory analyses involved extraction and qualitative
identification of secondary metabolites. The results revealed pronounced population
fragmentation and decline, primarily driven by grassland succession and overgrazing.
Metabolic profiling of the methanol leaf extract was performed using a UHPLC-Orbitrap/MS
instrument. Phytochemical screening confirmed the presence of valuable bioactive compounds,
with flavonoids and phenolic acids being the most abundant. These findings underscore the
urgent need for targeted conservation measures for P. montana, including long-term population
monitoring, habitat protection, and regulation of human-induced impacts. In addition to its
ecological importance, the presence of pharmacologically relevant compounds supports the
potential application of this species in phytotherapy and the development of natural
pharmaceutical products.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. 145
Seasonal Dynamics and Factors Shaping Aquatic Insect Assemblages in Mountain Streams of the Pannonian Lowland Ecoregion
No full textThis study focused on the aquatic insect orders that serve as biological indicators.
Ephemeroptera, Plecoptera, Trichoptera, Coleoptera, and Odonata were studied with their
relationships to physical, chemical, hydrological and morphological variables in 14 streams
on three Croatian mountains: Papuk, Medvednica and Psunj. From 675 samples collected
in three dominant sediment microhabitats (e.g., macrolithal and mesolithal) in each stream,
we identified 130 macroinvertebrate taxa. The most abundant group was Ephemeroptera
(36 taxa). Aquatic insect assemblages between Papuk and Psunj showed higher similarity
due to the geographical proximity of these two mountains, which is expressed as spatial
connectivity. In spring, greater variability and diversity of investigated aquatic insects
were observed due to the phenology of studied insects. The combination of environmental
and morphological properties (e.g., oxygen concentration and substrate type) had the
most significant influence on shaping the assemblage of aquatic insects of Psunj, while
morphological properties were the most important in shaping aquatic insect assemblages
on Papuk (e.g., streambed width) and Medvednica (e.g., elevation). Baetis sp. was the
dominant taxon in summer, Protonemura montana in spring, and Leuctra sp. in autumn.
Seasonal shifts in environmental conditions lead to functionally unique communities that
utilize the pool of available seasonal resources. The dominance of feeding groups varied
by season, with scrapers and collector–gatherers being most prevalent in summer, while
shredders were dominant in spring. The results on the relationships between environmental
characteristics and species richness, functional structure, and distribution of aquatic insects
in mountain streams provide important clues for future research and conservation strategies
in these vulnerable ecosystems