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Unveiling the antimicrobial, biofilm inhibition, and photoprotective potential of Bupleurum falcatum L. for dermatological applications
Bupleurum falcatum L. is known for its therapeutic properties, especially in treating fever, inflammation, and infectious diseases. However, its potential for dermatological applications remains mainly unexplored. Thus, present study explores antimicrobial potential of B. falcatum against biofilm-associated infections, antibiotic-resistant strains, and UV-induced skin damage. This aligns with the growing interest in natural products as sources of bioactive compounds with skin-protecting features. Herein, we employed maceration (M) and ultrasound-assisted extraction (USA) at 50 Hz and 100 Hz (USA 50 and USA 100) to obtain extracts from aerial parts of the plant. Chemical profiling was performed using UHPLC. Antimicrobial activity, biofilm inhibition, EPS and eDNA production were assessed using microdilution test, crystal violet, Congo red, and eDNA assays. Cytotoxicity and photoprotective effects were evaluated on human keratinocytes using MTT assay. Chemical analysis identified 64 compounds, including benzoic and cinnamic acid derivatives, flavonoid glycosides, and saikosaponins. Extracts showed strong antimicrobial activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MIC as low as 0.5 mg/mL). The M extract displayed moderate biofilm inhibition and reduced eDNA production. Cytotoxicity assays confirmed safety on keratinocytes, while M and USA 100 extracts demonstrated photoprotective effects. B. falcatum extracts show promise in addressing biofilm-associated infections, antibiotic resistance, and UV-induced skin damage
Institut za biološka istraživanja „Siniša Stanković“ – Institut od nacionalnog značaja za Republiku Srbiju, Univerzitet u Beogradu : bibliografija: 2024
Bibliografija Instituta za biološka istraživanja „Siniša Stanković“ (IBISS)-Instituta od nacuonalnog značaja za Republiku Srbiju, Univerziteta u Beogradu za 2023. godinu obuhvata rezultate koji su ostvareni realizaciojom Ugovora o realizaciji i finansiranju naučnoistraživačkog rada nio u 2024. godini, finansiran od strane Ministarstva prosvete, nauke i tehnološkog razvoja Republike Srbije., Evidencioni broj: 451-03-66/2024-03/200007, kao i rezultata međunarodnih projekata i ugovora u ovom periodu
Therapeutic effects of H₂S donors on ferroptosis-mediated liver damage in C57BL/6 mice – a microscopic study
Today, it is well known that diabetes (DM)-induced liver damage includes different types of cell death such as apoptosis, necrosis, autophagy and pyroptosis [1]. Recently, our group discovered that hepatocytes [2], as well as pancreatic β-cells [3], in diabetic condition are prone to ferroptosis, a regulated cell death initiated by iron-driven lipid peroxidation. Besides well-described oxidative imbalance in DM, it is less known that DM is also characterized by decreased level of hydrogen-sulfide (H2S) in peripheral tissues and the circulation [4]. Although H₂S has antiferroptotic properties, its role in DM-induced liver damage remains unclear. This study aimed to examine the antiferroptotic effects of three H₂S/reactive sulfur species (RSS) donors in the diabetic liver. DM was induced in male C57BL/6 mice with one i.p. STZ injection (150 mg/kg). Two months after DM induction, synthetic H2S donors: (1) direct H2S donor – GYY4137, (2) polysulfide donor – Sodium sulfide (Na2S4) and (3) persulfide donor – cysteine-3-sulfide (Cys-S3) were i.p. administered, for one month. After treatments ended, mice were sacrificed, afterwards blood and liver were collected and processed for further biochemical, microscopical and molecular analyses. As shown in Figure 1, treatment with H2S donors led to amelioration of diabetes-induced increase in glycemia, glycosuria and ALT level. In accordance with the improvement of biochemical parameters, morphological and morphometric analysis of liver revealed reduced fibrosis and less DM-induced hypertrophy and binucleation of hepatocytes in groups treated with GYY and Cys-S3. Figure 1: Biochemical and morphological parameters. Glucose level in serum (a) and urine (b), serum ALT (c) and AST (d) activity. H&E (e) and AZAN (f) staining of liver. Quantification of binucleation (g), profile area (h) of hepatocytes, and level of fibrosis in liver (i). 227 Regarding the signs of ferroptosis – free iron and lipofuscin accumulation (Figure 2; quantification – 2b and 2c) were significantly decreased in Na2S4 and Cys-S3 treated groups, while Cys-S3 also decreased DM-induced lipid peroxidation (lowered 4-HNE immunopositivity, Figure 2d). Regarding immunopositivity of the main enzyme involved in the removal of lipid peroxides in the membrane, GPX4, a tendency to return to control levels was observed in the hepatocytes of mice treated with Na2S4 and Cys-S3 (Figure 2e). These findings highlight the potent antiferroptotic effects of H₂S donors and point to a novel strategy for preventing or treating diabetes by modulating ferroptosis through H₂S signalling.Book of abstracts : 17th Multinational Congress on Microscopy : 17MCM; 2025 Sep 7-12; Portorož, Slovenia. Ljubljana : Slovene Society for Microscopy; 2025. p. 227-8
Improved methodology for estimating the rainfall erosivity factor (R)
У раду је приказана унапређена методологија за одређивање вредности
фактора ерозионе снаге кише R, најзначајнијег фактора једначине USLE за прорачун
губитака земљишта (Universal Soil Loss Equatation). Унапређење методологије
огледа се кроз увођење ерозивности падавина слабијих интензитета и дужег трајања
у облику кише или снега, у периоду када не раде плувиографи (новембар – март).
Вредности фактора Rgod омогућавају поређење са резултатима добијеним у европским
земљама, где се последњих 60 година интензивно ради на прилагођавању поменуте
методологије локалним условима. Вредности емпиријског коефицијента b0 који
омогућава једноставнији обрачун коришћењем сума средњих месечних падавина, су
у нашим истраживањима неправилно коришћене (усвајане су вредности из опсега
који је дефинисан за Италију). Вредности b0 добијене на основу података очитаних
са плувиографских трака и увођењем ерозивности падавина у зимским месецима за
3 климатолошке станице у Србији крећу се од 1,34 до 1,75. Правилно одређивање
вредности фактора R је од изузетног значаја за примену методологије USLE у нашим
условима и израду Карте ерозије Србије.U radu je prikazana unapređena metodologija za određivanje vrednosti faktora erozione snage kiše R, najznačajnijeg faktora jednačine USLE za proračun gubitaka zemljišta (Universal Soil Loss Equatation). Unapređenje metodologije ogleda se kroz uvođenje erozivnosti padavina slabijih intenziteta i dužeg trajanja u obliku kiše ili snega, u periodu kada ne rade pluviografi (novembar - mart). Vrednosti faktora R God omogućavaju poređenje sa rezultatima dobijenim u evropskim zemljama, gde se poslednjih 60 godina intenzivno radi na prilagođavanju pomenute metodologije lokalnim uslovima. Vrednosti empirijskog koeficijenta b0 koji omogućava jednostavniji obračun korišćenjem suma srednjih mesečnih padavina, su u našim istraživanjima nepravilno korišćene (usvajane su vrednosti iz opsega koji je definisan za Italiju). Vrednosti b0 dobijene na osnovu podataka očitanih sa pluviografskih traka i uvođenjem erozivnosti padavina u zimskim mesecima za 3 klimatološke stanice u Srbiji kreću se od 1,34 do 1,75. Pravilno određivanje vrednosti faktora R je od izuzetnog značaja za primenu metodologije USLE u našim uslovima i izradu Karte erozije Srbije.In this paper, an improved methodology for estimating the rainfall erosivity factor
(R), the most important factor in the USLE (Universal Soil Loss Equation) equation for calcu-
lating soil loss, is proposed. The improvement of the methodology is reflected in the introduc-
tion of the erosiveness of precipitation with lower intensity and longer duration in the form of
rain or snow, during the period when pluviographs are not operating (November–March). The
values of the Ryear factor allow for comparison with the results obtained in European countries,
where intensive work has been carried out over the past 60 years to adjust the aforementioned
methodology to local conditions. On the other hand, the values of the empirical coefficient b0,
which allows for a simpler calculation using the sum of average monthly precipitation, were
incorrectly used in Serbia (i.e., values from the range defined for Italy were adopted). Based on
the data read from pluviographic strips charts and the introduction of precipitation erosivity for
the winter months from three climatological stations in Serbia, the b0 values ranged from 1.34 66I
to 1.75. The correct determination of the R-factor is of utmost importance for the application of
the USLE methodology in local conditions and the preparation of the Erosion Map of Serbia
The effect of hydrogen (per)sulfide donors on β-cells ferroptosis in diabetic conditions
Hydrogen sulfide (H2S) is an important gassotransmiter which level is reduced in diabetic state. Although its donors represent an innovative approach in the treatment of some diabetes-related pathologies, its role in the regulation of function/destiny of β-cells has not been elucidated. We examined the effects of slow releasing H2S donor (GYY4132), polysulfide (Na2S4) and persulfide (Cys-3S) donors on β-cells ferroptosis under diabetic conditions in vitro and in vivo.
Cys-3S had positive effects on diabetes-induced proferroptotic events (accumulation of iron and lipid peroxides and failure of the antiferroptotic axis, Nrf2/xCT/GPX4/GSH) in pancreatic islets in vivo, which was reflected in the maintenance of the functional population of β-cells, serum glucose level and decrease in diabetes incidence. In parallel, the expression of CSE in pancreatic islets was significantly upregulated by Cys-3S treatment. The results from in vitro study confirm its strong antiferroptotic potential: Cys-3S prevented high glucose- and RSL-3-induced β-cell death in similar manner as established ferroptosis inhibitor Fer-1. Na2S4 also acted beneficially on the ferroptotic parameters and pancreatic CSE level, but failed to maintain β-cell population and stabilize hyperglycemia in diabetic animals. The effects of GYY4137 on diabetes-induced changes in systemic or tissue ferroptotic parameters were less pronounced and complete.
Although both donors of polysulfide and persulfide ameliorated diabetes-induced ferroptotic phenotype of β-cells and disturbances in H2S biosynthetic pathways, only in the case of Cys-3S antidiabetic effect and better metabolic control was achieved. This qualifies direct donors of persulfides as a effective approach in the prevention of β-cells death and diabetes development.Abstract book: EMBO WORKSHOP: Thiol based thiol switches; From chemistry to physiology and pathology; 2025 Sep 13-18; Sant Feliu de Guixols, Spain. Heidelberg: EMBO Press; 2025. p. P75
Утицај различитих услова гајења на хемијски састав листова врсте Nepeta nuda
Nepeta nuda je široko rasprostranjena vrsta ovog roda koja se u Srbiji može naći južno od Save i Dunava, a karakteriše se sadržajem velikog broja bioaktivnih jedinjenja poput različitih monoterpena (uključujući i iridoide), diterpena, seskuiterpena kao i fenolnih jedinjenja. Gajenje vrste Nepeta nuda u stakleniku i u in vitro uslovima ukazalo je da se specijalizovani metabolizam ove vrste značajno menja u zavisnosti od uslova gajenja. Kvantitativna UHPLC/DAD/(±)HESI-MS² analiza listova Nepeta nuda gajenih u različitim uslovima bila je usmerena na šest iridoidnih jedinjenja (nepetazid, 1,5,9-epi-deoksiloganičnu kiselinu, nepetanudozid, 5,9-dehidronepetalakton, cis,trans- i trans,trans-nepetalakton), kao i na pet fenolnih jedinjenja (kvercetin, luteolin, ruzmarinsku, kofeinsku i hlorogensku kiselinu). Dok su listovi biljaka gajenih u in vitro uslovima bili bogatiji isparljivim iridoidnim jedinjenjima, pre svega usled visoke koncentracije dehidronepetalaktona, koncentracija fenolnih jedinjenja bila je značajno viša u listovima biljaka gajenih u stakleniku. Analizirani listovi karakterisali su se niskim koncentracijama iridoidnog aglikona nepetalaktona, pri čemu je u listovima in vitro biljaka detektovan trans,trans- dok je kod biljaka gajenih u stakleniku preovladao cis,trans-nepetalakton. GC-MS analiza je takođe ukazala na veću zastupljenost iridoidnih jedinjenja u listovima biljaka gajenih u in vitro uslovima. Prisustvo različitih terpenskih jedinjenja poput beta-farnesena, fitola i skvalena detektovano je samo kod biljaka gajenih in vitro, dok su 1,8-cineol i pinanediol detektovani samo u listovima biljaka gajenih u stakleniku. Dobijeni rezultati ukazuju na značajan uticaj uslova gajenja na kvantitativan i kvalitativan sastav specijalizovanih metabolita u listovima Nepeta nuda, što omogućava optimizaciju uslova gajenja u cilju produkcije željenih bioaktivnih jedinjenja.Nepeta nuda је широко распрострањена врста овог рода која се у Србији може наћи
јужно од Саве и Дунава, а карактерише се садржајем великог броја биоактивних једи-
њења попут различитих монотерпена (укључујући и иридоиде), дитерпена, сескви-
терпена као и фенолних једињења. Гајење врсте Nepeta nuda у стакленику и у in vitro
условима указало је да се специјализовани метаболизам ове врсте значајно мења
у зависности од услова гајења. Квантитативна UHPLC/DAD/(±)HESI-MS² анализа
листова Nepeta nuda гајених у различитим условима била је усмерена на шест ири-
доидних једињења (непетазид, 1,5,9-epi-деоксилоганинску киселину, непетанудозид,
5,9-дехидронепеталактон, cis,trans- и trans,trans-непеталактон), као и на пет фенолних
једињења (кверцетин, лутеолин, рузмаринску, кафеинску и хлорогенску киселину).
Док су листови биљака гајених у in vitro условима били богатији испарљивим иридо-
идним једињењима, превасходно услед високе концентрације дехидронепеталактона,
концентрација фенолних једињења била је значајно виша у листовима биљака гајених
у стакленику. Анализирани листови карактерисали су се ниским концентрацијама ири-
доидног агликона непеталактона, при чему је у листовима in vitro биљака детектован
trans,trans- док је код биљака гајених у стакленику преовладао cis,trans-непеталактон.
GC-MS анализа је такође указала на већу заступљеност иридоидних једињења у листо-
вима биљака гајених у in vitro условима. Присуство различитих терпенских једињења
попут бета-фарнесена, фитола и сквалена детектовано је само код биљака гајених in
vitro, док су 1,8 цинеол и пинанедиол детектовани само у листовима биљака гајених у
стакленику. Добијени резултати указују на значајан утицај услова гајења на квантита-
тиван и квалитативан састав специјализованих метаболита у листовима Nepeta nuda,
што омогућава оптимизацију услова гајења у циљу продукције жељених биоактивних
једињења.Stanković M, Bojović B, Stefanović O, Kosanić M, Milutinović M, editors. Program i izvodi saopštenja: Druga konferencija srpskog biološkog društva "Stevan Jakovljević" Kragujevac; 2025 Sep 17-19; Kragujevac, Serbia. Kragujevac: Srpsko biološko društvo "Stavan Jakovljević"; 2025. p. 103
A new record of the Greek frog at the northern border of the species area
The Greek frog (Rana graeca) is a European species, endemic to the Balkan Peninsula. This brown frog inhabits hilly/mountain
areas where it almost exclusively spawns in fast-running streams and rivers. The northern border of the species distribution range
spreads from northwestern Bosnia & Herzegovina to northwestern Serbia and then shifts towards the southeastern Balkans. The new
records noticed in the central part of Serbia (Šumadija) suggest that the presence of the Greek frog could be easily overlooked if a
locality is not inspected at the right time of the year. Possible suitable habitats positioned more to the north from the present northern
contours of the species area should be thoroughly explored
Evaluating the Effect of Sauerkraut Brine on Oxidative Stress and Inflammatory Response in C57BL/6 Mice
Systemic inflammation, often triggered by bacterial components such as
lipopolysaccharide (LPS), activates cytokine-driven immune responses. This
process can be modulated by various nutritional interventions, including
consumption of fermented foods, rich in bioactive compounds with known antiinflammatory
and immunomodulatory effects. The effects of sauerkraut brine (SB)
on LPS-induced inflammation in C57BL/6 mice were investigated in this study. In
the first experiment, mice were treated either with sauerkraut brine (SB)-treated, or
saline (S). In the second experiment, animals received fecal transplants from SB
treated (FT-SB) or S-treated (FT-S) donors. All animals were exposed to LPSinduced
inflammation three hours before sacrifice. The activity of oxidative
enzymes and level of inflammatory cytokines levels were analyzed in the cerebral
cortex. Treatment with SB resulted in a significant reduction of cytokine expression
in the cerebral cortex by modulating the TLR4-MyD88 signaling pathway,
suggesting a tissue-specific anti inflammatory effect. Experiments with fecal
transplantation indicate that these effects may be mediated by gut microbiota.
This study supports the therapeutic potential of fermented foods in modulating
neuroinflammatory processes.Dragić M, editor. Book of abstracts: 9th Congress of Serbian Neuroscience Society; 2025 Oct 6-8; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2025
Microplastic occurrence in gastrointestinal tracts of freshwater fish: addressing data gaps in Serbia and adjacent countries
Among various environmental pollutants, microplastics (MPs) have become one of the most pressing environmental problems of the 21st century due to their ubiquitous distribution in global ecosystems. The widespread distribution of MP is due to their inherent chemical stability and very slow biodegradation, which allow them to persist in environmental systems over long periods of time with minimal structural changes.
Once dispersed in the environment, MPs are difficult to remove and can end up in drinking water and aquatic food sources, harming both the environment and human health. While the presence of MPs in the marine environment has been identified worldwide, the importance of MP pollution in the freshwater environment has also been emphasised in recent years. Several field studies have reported the presence of MPs in the gut contents of fish in freshwater habitats [1, 2]. The aim of our study was to highlight the need of investigation of the occurrence of MPs in the gut contents of freshwater fish from Serbia and its bordering countries (Slovenia, Croatia, Montenegro, Bosnia and Herzegovina, North Macedonia, Albania, Hungary, Bulgaria and Romania). The literature review was conducted as part of the Interreg Ipa-Adrion project, ADRIPLAST, which highlighted the general lack of data on MP in freshwater fish. In the current literature, there are only a few publications that deal specifically with MP in the gastrointestinal tract of freshwater fish, while most research has focussed on the presence of MPs in the aquatic environment (in water and sediment matrices). Although the results are relatively scarce, a few studies have been reported from the Eastern European countries, including Romania [3, 4], Slovenia [5], Croatia [6, 7], and Serbia [8]. These results emphasise the need for a systematic and comprehensive investigation of MP contamination of freshwater fish species in these regions. Edible fish species deserve special attention as they play a direct role in the human diet and are therefore a critical vector for the transfer of MPs) into the human food chain. Therefore, the ingestion and accumulation of MPs by these fish can lead to potential human exposure, raising concerns about the toxicological and health effects of microplastic pollution. The analysis of MP in freshwater fish provides important data for environmental monitoring, ecological risk assessment, fisheries management and ultimately contributes to the protection of public health.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. 10
Metal bioaccumulation in muscle tissue of the northern pike Esox lucius Linnaeus, 1758 from Tisza River
Fish inhabiting contaminated aquatic environment tend to accumulate essential, but also toxic metals in their tissues. The extent of metal accumulation is influenced by several factors, including metal concentration in the environment, duration and frequency of exposure, mechanisms of metal uptake and intrinsic factors such as fish age, sex, or feeding habits. Various metals, depending on their type and role, have a different affinity to fish tissues. Fish muscles usually contain the lowest amounts of metals compared to other tissues, but are often used in studies because they are a part of the fish body used in the human nutrition [1, 2].
The northern pike is the top piscivore and a phytophilic species in a trophic pyramid of freshwater ecosystems that is highly dependent on backwaters and vegetated riverine areas for spawning and recruitment. In the autumn season 2024, 11 samples of northern pike were collected from the Tisza River using electrofishing (HONDA 1.2кW, 6 А). The content of metals (Ag, Al, As, Cd, Cr, Co, Cu, Fe, Li, Mn, Ni, Pb, Sr, Zn) was determined in muscle samples of fish of different ages using inductively coupled plasma optical spectrometry (ICP-OES). The age determination indicated that the sampled fish ranged from age classes 1+ to 5+. This study aimed to evaluate the potential human health risk associated with the consumption of fish muscle by calculating the estimated daily intake (EDI) of metals, following the methodology described by Javed and Usmani [3]. The risk assessment of metal exposure determined by parameters such as the EDI, involves not only the amount of contaminant ingested, but also factors such as the frequency and duration of exposure, the average body weight of the fish, and the oral reference dose.
Notably, nickel (Ni) and cobalt (Co) were below detection limits in the analyzed fish muscle samples. The concentrations of other detected metals were below the maximum concentrations set by the EU [4] and the Republic of Serbia [5]. The observed values for EDI were significantly lower than the corresponding reference doses, therefore all confirming safe human consumption.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. 109