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Blood serum indicators of cognitive impairment in peripubertal rats in-utero exposed to ELF-MF
No full textLong-term changes in serum albumin, total protein, total cholesterol, creatinine, and
Ca2+ concentrations may be associated with cognitive impairment. However, the
definitive role of these blood parameters in cognitive functions has not yet been
conclusively clarified. An extremely low-frequency magnetic field (ELF-MF)
generated by domestic installations, household appliances, and power grids has
been associated with various short- and long-term (neuro)physiological and
neuropsychological effects in humans. This study addresses the effect of
continuous in-utero exposure to ELF-MF (50 Hz, 0.5 mT) on the concentrations of
these potential serum indicators of cognitive impairment in peripubertal rats. Adult
male and female rats (Wistar IGS) were placed near the on/off electromagnet
generating ELF-MF (50 Hz, 0.5 mT) until conception. The pregnant females were
further exposed to ELF-MF until the offspring were born. Immediately after birth,
the mothers and their offspring were removed from the ELF-MF exposure system.
Between 09:00 and 10:00 on the postnatal days 40-42 blood samples were taken
from the trunk of each animal, and the sera were isolated and stored at -80°C until
analysis. Serum parameters were analyzed using an automated biochemical
analyzer (BS-240 Vet). The Kruskal-Wallis and Mann-Whitney tests were used to
evaluate the changes in each parameter. Continuous in-utero exposure to ELF-MF
causes the following significant effects in peripubertal offspring: (1) Decreased
albumin concentration in males, (2) Decreased total cholesterol concentration in
males, (3) Decreased creatinine concentration in males and increased creatinine
concentration in females, and (4) Decreased Ca2+ concentration in males and
increased Ca2+ concentration in females. These results suggest that continuous
in-utero exposure to ELF-MF may affect blood serum indicators of cognitive
impairment in peripubertal rats.Dragić M, editor. Book of abstracts: 9th Congress of Serbian Neuroscience Society; 2025 Oct 6-8; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2025
Novel pyrimidine-artesunate hybrids overcome multidrug-resistance in non-small cell lung carcinoma through collateral sensitivity
No full textA series of hybrid compounds based on artesunic acid and pyrimidine were synthesized and tested for their anticancer activity against non-small cell lung carcinoma (NSCLC), specifically targeting multidrug resistance mediated by P-glycoprotein (P-gp). Preliminary screening showed that artesunate and the hybrid compounds exhibited enhanced cytotoxicity towards resistant NCI-H460/R cells at 5 μM, indicating collateral sensitivity. Dose-response analysis identified compounds 15h and 17a with the most substantial effect, displaying collateral sensitivity indexes (CSI) 4 and 5, respectively, while 15d, 15f, and 15i showed remarkable selectivity for cancer cells with selectivity indexes (SI) above 10. Mechanistic studies revealed that some hybrids effectively inhibited P-gp activity, outperforming the benchmark inhibitor tariquidar (TQ). Co-treatment of 15h and 17a with P-gp inhibitors indicated that the type of P-gp inhibition matters. Substrate inhibitor dexverapamil (Dex-Ver) lowered cytotoxicity of 15h and 17a, while non-substrate inhibitor TQ, increased it. Computational docking study showed that 17a binds the verapamil-binding pocket of P-gp with greater affinity than dexverapamil (Dex-Ver). The P-gp mechanism and the difference in redox balance between sensitive and resistant NSCLC cells drive collateral sensitivity achieved by 15h and 17a. Overall, the study demonstrates that pyrimidine-artesunate hybrids selectively target MDR cancer cells, highlighting their potential to overcome drug resistance in cancer treatment
Strain-Dependent Differences in Inflammatory/Immune Activity in Cutaneous Wound Tissue Repair in Rats: The Significance of Body Mass/Proneness to Obesity
No full textInflammatory/immune cells and mediators are substantial for wound healing because they orchestrate biological activities in this
complex process. Among factors that affect wound healing, obesity, and metabolic diseases are among the most significant,
particularly because of a relationship between obesity and a prediabetic state with immune reactivity. Using Dark Agouti (DA)
and Albino Oxford (AO) rats, which differ in immune responses as well as in proneness to obesity, we examined the impact of these
intrinsic factors on cutaneous wound healing. Dynamics of the process were monitored at days 3, 5, and 7 post-wounding parallel
in both rat strains by analysis of selected basic aspects of the wound repair process (cytokine and growth factor responses) in
granulation tissue. Strain-related differences in the extent of reduction of the wound area were shown, which coincided with
differential proinflammatory and immune-regulatory cytokines, as well as growth factors response in these rats. Some of these
differences seem related to their dissimilarities in the proneness to obesity. Results in this study extended so far known differences
in inflammatory/immune responses to a variety of stimuli between AO and DA rats and showed, for the first time, immune-based
differences in wound healing between rats that differ in body mass (BM) and obesity proneness (under ad libitum feeding
conditions with normal rodent chow)
Agmatine suppresses glycolysis via the PI3K/Akt/mTOR/HIF-1α signaling pathway and improves mitochondrial function in microglia exposed to lipopolysaccharide
No full textModulating metabolic pathways in activated microglia can alter their phenotype, which is relevant in uncontrolled neuroinflammation as a component of various neurodegenerative diseases. Here, we investigated how pretreatment with agmatine, an endogenous polyamine, affects metabolic changes in an in vitro model of neuroinflammation, a murine microglial BV-2 cell line exposed to lipopolysaccharide (LPS). Hence, we analyzed gene expression using qPCR and protein levels using Western blot and ELISA. Microglial metabolic status was assessed by measuring lactate release and cellular ATP by enzymatic and luminescence spectrophotometry. Mitochondrial functionality was analyzed by fluorescent probes detecting mitochondrial membrane potential (mtMP) and superoxide production. Our findings suggest that kinase pathways associated with hypoxia-inducible factor-1α (HIF-1α) regulate energy metabolism in pro-inflammatory activated microglia. We have shown that LPS induces HIF-1α and genes for glucose transporter and glycolytic rate, increases lactate production and causes mitochondrial dysfunction, suggesting a metabolic shift towards glycolysis. Agmatine inhibits the PI3K/Akt pathway and negatively regulates mammalian target of rapamycin (mTOR) phosphorylation and HIF-1α levels, reducing lactate and tumor necrosis factor (TNF) production, which is supported by pharmacological blockade of PI3K. Pretreatment with agmatine also rescues mitochondrial function by counteracting the LPS-induced decline in mtMP and increase in mitochondrial superoxide, resulting in an anti-apoptotic effect. Agmatine alone increases intracellular ATP levels and maintains this effect even under pro-inflammatory conditions. Our study emphasizes the ability of agmatine to engage in metabolic reprogramming of pro-inflammatory microglia through increased ATP production and modulation of signaling pathway involved in promoting glycolysis and cytokine release
Ecological status and phytochemical potential of Rindera umbellata in the Deliblato sands
No full textRindera umbellata (Waldst. & Kit.) Bunge (fam. Boraginaceae) is distributed in southeast
Europe, from the Central Balkan Peninsula to southwest Ukraine. In Serbia, R. umbellata
occurs only in the Deliblato and Kladovo Sands, with isolated populations inhabiting specific
dry, sandy habitats. R. umbellata is listed in the Red List of the Flora of Serbia as a rare and
endangered plant species and is protected under national legislation, reflecting its threatened
status and conservation priority. The aim of this study was to assess the population status of R.
umbellata in the Deliblato Sands, identify the main threats, and conduct phytochemical
profiling to determine bioactive compounds. Fieldwork included mapping localities, visual
estimation of individual abundance, and analysis of habitat characteristics. Metabolic profiling
of methanol leaf extract was performed using a UHPLC-Orbitrap/MS instrument. Results
indicate a fragmented and numerically limited population, threatened by succession, invasive
species, and anthropogenic activities. Qualitative phytochemical analysis shows that the leaves
of R. umbellata collected in nature are a rich source of flavonoids and phenolic acids. Among
the flavonoids, the most dominant compounds were quercetin 3,7- diglucoside and rutin, while
rosmarinic acid was the most abundant phenolic acid. The findings highlight the urgent need
for conservation of this species through active habitat protection, management of adverse
factors, and implementation of regular monitoring.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. 146
De Novo Transcriptome Assembly of Nepeta grandiflora L. leaf trichomes and trichome-depleted leaves
No full textAssembled transcriptomes from paired-end RNA sequencing of Nepeta grandiflora L. leaf trichomes and trichome-depleted leaves using DNBSEQ, in FASTA format. The dataset comprises 248961 assembled transcripts. N. grandiflora transcriptome data are a part of phyloNEPETOME data platform
Antimicrobial Effect of Boswellia serrata Resin’s Methanolic Extracts Against Skin Infection Pathogens
No full textFrankincense resin (Boswellia serrata), native to arid regions of India, the Mid‑
dle East, and parts of Africa, has been highly valued for its medicinal properties. This
study evaluated the antimicrobial potential of methanolic extracts of Boswellia serrata resin
against Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria monocytogenes. High‑
performance thin‑layer chromatography (HPTLC) coupled with bioautography identified
bioactive zones, while Liquid Chromatography–Mass Spectrometry (LC‑MS) quantified
the phenolic and terpenoid compounds. The cytotoxicity was assessed on HaCaT hu‑
man keratinocyte cells to evaluate the safety for dermatological applications. The results
demonstrated significant antibacterial activity, particularly against S. aureus and L. monocy‑
togenes. The bioautograms revealed that samples from central and southern Serbia showed
the highest antimicrobial effect against the tested bacterial strains. The active compounds
included 11‑keto‑β‑boswellic acid (up to 3733.96 μg/g), gallic acid (110.93 μg/g), and narin‑
genin (53.13 μg/g). Cytotoxicity assays confirmed non‑toxic effects at 10 μg/mL, with sam‑
ple 6 enhancing the keratinocyte viability by 137%, while higher concentrations (50 μg/mL)
showed variable cytotoxicity. These findings highlight the potential of B. serrata resin as
a natural antimicrobial agent, particularly against antibiotic‑resistant pathogens. Its ther‑
apeutic applicability in pharmaceutical and cosmetic formulations is promising provided
that dosing ensures a balance between efficacy and safety
Innate lymphoid cells: Dual roles and therapeutic opportunities in breast cancer
No full textInnate lymphoid cells (ILC) play a crucial role in shaping immune responses and maintaining tissue homeostasis. Recent research has identified their involvement in breast cancer pathogenesis, mainly through shaping the tumor microenvironment, where they can exert dual roles, either promoting tumor eradication by enhancing anti-tumor immunity, or facilitating tumor progression through mechanisms of immune evasion. This functional plasticity makes ILC attractive targets for immunotherapy. Furthermore, their slow proliferation enables them to survive anti-proliferative radiation therapy and chemotherapy, which may support continuous immune surveillance of breast cancer tissue. However, this same resilience poses a significant challenge, as surviving ILC could contribute to tumor persistence or recurrence. Additionally, anti-estrogen therapy, chemotherapy and immune checkpoint inhibitors, commonly used in breast cancer treatment, may interfere with ILC function, either dampening their anti-tumor potential or enhancing their pro-tumor activities. Understanding the complex interactions between ILC and conventional therapies is critical for designing effective immunotherapeutic approaches that include ILC targeting, potentially overcoming resistance and improving patient outcomes in breast cancer therapy
Bioactive potential of Tripleurospermum inodorum with detailed insight into anti-inflammatory activity through in vitro, in vivo evaluations and network pharmacology
No full textThis study evaluated Tripleurospermum inodorum extract for cytotoxic, anti-inflammatory, antioxidant, antimicrobial, and antibiofilm properties, alongside its phenolic profile, predicted pharmacological interactions and in vivo anti-inflammatory properties. The methanolic extract of T. inodorum was rich in apigenin derivatives, including apigenin-O-pentoside (5.234 mg/g) and apigenin-O-acetyl hexoside (4.929 mg/g), as identified using LC-DAD-ESI/MSⁿ. The extract demonstrated potent anti-inflammatory activity (IC₅₀ = 8.4 µg/mL) by inhibiting nitric oxide production in a RAW 264.7 macrophage model, a key mechanism in controlling inflammatory responses. Its cytotoxicity against NCI-H460 lung carcinoma cells (GI₅₀ = 62.9 µg/mL) suggests potential for targeting inflammation-driven carcinogenesis. Antioxidant activity, ranging from 204.4 (FRAP) to 442.2 (ABTS) mmol of gallic acid equivalents per 100 mg dry weight, highlights its role in mitigating oxidative stress-a critical driver of chronic inflammation. The extract also displayed moderate antimicrobial activity (MIC: 3-12 mg/mL) and strong antibiofilm potential (> 70% inhibition in a crystal violet assay), which are essential for managing infection-associated inflammation. Network pharmacology revealed that dominant phenolic compound act as aldose reductase inhibitors, targeting inflammatory pathways linked to metabolic stress. In vivo assessment using a xylene-induced ear edema model revealed a dose-dependent, biphasic anti-inflammatory effect, with lower doses (125 and 250 mg/kg) exhibiting greater efficacy compared to the highest dose (500 mg/kg), suggesting a hormetic response that emphasizes the importance of optimal dosing. These findings indicate that the methanolic extract of T. inodorum possesses a broad spectrum of bioactivities relevant to inflammation control and supports its further development as a source of novel anti-inflammatory therapeutics
Development and Characterization of a Temozolomide-Resistant Human Glioblastoma Cell Line
No full textGlioblastoma is the most lethal form of brain cancer, with a median survival of only 14 months.
The poor prognosis is largely associated with development of resistance to temozolomide (TMZ),
the first-line chemotherapy and standard of care for glioblastoma patients. Therefore, reliable
preclinical models of TMZ resistance are essential for developing strategies translatable to clinical
practice. To develop a clinically relevant in vitro resistance model reflecting the cyclic TMZ
dosing used in the Stupp protocol (5-day treatment/3-week break), we adapted a culturecompatible regimen. We exposed the TMZ-sensitive A-172 human glioblastoma cell line to 10 µM
TMZ for two 3-day treatment cycles, each followed by a 3-week recovery. We assessed TMZ
sensitivity in parental and treated cells using the MTT assay after one, two, and three days of TMZ
exposure. Additionally, we performed wound healing and EGFR immunostaining assays.
Compared to the parental line, IC₅₀ values increased progressively: from 136.2 to 1582 µM (single
treatment), 60.1 to 377.2 µM (double treatment), and 32.74 to 206 µM (triple treatment), indicating
a gradual resistance development. In the wound healing assay, the resistant line showed slower
gap closure: after 72 h, the sensitive line nearly closed the wound, while the resistant line exhibited
2-fold slower closure kinetics. EGFR immunostaining indicated a slight increase in expression in
resistant cells. The cyclic TMZ regimen adapted for in vitro use successfully induced resistance in
A-172 cells, generating a cell line with reduced migratory capacity and slightly elevated EGFR
expression.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. 11