BIOREpository (Faculty of Biology, University of Belgrade)
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    Nrf2-driven redox coupling of tumour and associated adipose tissue during early tumour growth in an orthotopic breast cancer model

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    The redox-based two-way communication between breast cancer cells and their tumour microenvironment (TME) contributes significantly to the establishment of the malignant phenotype. Due to its well-established role in redox-metabolic reprogramming, Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) has emerged as a potentially key player in the bilateral interaction between breast cancer cells and cancer-associated adipose tissue (CAAT), the main cellular component of the TME. In this study, we used an orthotopic model of Nrf2+/+ luminal type B breast cancer in wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2KO) to investigate the role of Nrf2-driven redox coupling between breast cancer and CAAT. To this end, we examined the expression profiles, localisation, and activity of the main antioxidant defence (AD) enzymes in breast tumour tissue in the Nrf2+/+ or Nrf2-/- host environment at different phases of early tumour growth. In addition, we analysed key enzymes involved in nicotinamide adenine dinucleotide phosphate (NADPH) metabolism. We demonstrate the establishment of a distinct redox profile of breast cancer cells in the Nrf2-/- TME when compared to WT TME. Furthermore, the activity and protein levels of AD enzymes in CAAT showed both Nrf2-dependent and/or tumour-dependent changes. Taken together, these results highlight the importance of Nrf2-driven modulations in the host TME for establishing the redox profile of breast cancer. Moreover, the initial phase of early tumour growth appears most susceptible to the absence of functional Nrf2 in the host TME, thus providing a new potential therapeutic target point for breast cancer therapy.M21a8.2637923

    Repetitive transcranial magnetic stimulation as a universal modulator of synaptic plasticity: Bridging the gap between functional and structural plasticity

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    Repetitive transcranial magnetic stimulation (rTMS) is a painless and non-invasive technique for neuromodulation that has shown great potential in therapy of several neurodegenerative and neuropsychiatric disorders both in patients and animal models. In addition to its non-invasiveness, the main rationale for using it for these disorders is that the positive effects extend beyond the stimulation period and can last up to several minutes, hours or even days after the last application. While the mechanisms underlying these long-lasting positive effects have not yet been fully deciphered, current literature supports hypothesis of modulation of both functional and structural plasticity. Dendritic spines are structures on dendritic branches that regulate synaptic transmission at the level of postsynapse and represent one of the structural and functional carriers of synaptic plasticity. Since rTMS has been proposed to induce long-term potentiation/long-term depression-like effects, based on the existing literature in animal studies, we suggest several molecular mechanisms which could underpin rTMS-induced structural plasticity manifested at the level of dendritic spines that include processes starting from spinogenesis to gradual spine maturation and eventual spine shrinkage and loss. The results gathered in this review postulate rTMS as a universal modulator of synaptic plasticity, which could guide future research and help in optimizing appropriate protocols of transcranial magnetic stimulation for adequate disorders and pathologies.M214.410602118

    ST1-YtnP lactonase from extreme environment: A promising antivirulence agent against multidrug-resistant Pseudomonas aeruginosa

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    The emergence of multidrug-resistant (MDR) pathogens, particularly Pseudomonas aeruginosa, requires innovative therapeutic strategies. This study investigates the potential of ST1-YtnP lactonase, an enzyme isolated from the thermophilic bacterium Bacillus licheniformis, which is found in the extreme environment of the Vranjska Banja hot springs. The extreme conditions in this habitat offer untapped potential for the discovery of biotechnologically valuable, resilient enzymes. ST1-YtnP lactonase was shown to effectively degrade acyl-homoserine lactones (AHLs), thereby disrupting the quorum sensing (QS) system of P. aeruginosa and reducing its virulence. ST1-YtnP significantly reduced biofilm formation without inhibiting bacterial growth Furthermore, in vitro analysis revealed that ST1-YtnP lactonase exhibited a synergistic effect with gentamicin and an additive effect with meropenem, enhancing the efficacy of these antibiotics against P. aeruginosa MMA83. In vivo, the combination of meropenem and ST1-YtnP lactonase completely rescued Caenorhabditis elegans from infection, surpassing the protective effect of meropenem alone. ST1-YtnP lactonase showed no adverse effects on the survival of uninfected nematodes, while it significantly enhanced the survival of P. aeruginosa-infected nematodes treated with the enzyme. These findings emphasize the potential of ST1-YtnP lactonase as a novel antivirulence agent with promising biotechnological applications to combat antibiotic-resistant infections.M21a7,511844319

    The High Level of Between-Year Burrow Reuse in a European Bee-Eater Merops apiaster Colony

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    In this paper, we report a high level of burrow reuse by European bee-eaters (Merops apiaster) in a mixed colony shared with common starlings (Sturnus vulgaris) and common swifts (Apus apus) at Višnjička Kosa, a suburban area of Belgrade, Serbia. The study was conducted during the breeding season in 2023 and 2024. Of the 255 burrows examined in 2024, 123 (48.23%) had been used in a previous breeding year, 88 (34.51%) were completely or partially excavated prior to 2024 but not used in 2023 and 36 (14.12%) were newly excavated in 2024. These results demonstrate a substantial level of burrow reuse within the studied colony, suggesting that reusing existing burrows may allow birds to conserve the energy and time otherwise required for new excavation.M230.532733177

    Detection of Echinococcus multilocularis in animals in Serbia

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    Objectives: Alveolar echinococcosis (AE) caused by the fox tapeworm Echinococcusmultilocularis is an emerging disease in Serbia, with two confirmed cases in humans. Oneobjective of the Worm_Profiler project is the detection and mapping of the occurrenceof E. multilocularis in different animal species in order to gain a better understanding ofthe distribution and major reservoirs.Materials and methods: Adult worms were collected from the intestines of goldenjackals (Canis aureus) while Taeniid eggs were collected from jackal feces using a flotationand mesh filtration technique. Tissue and cyst fluid, if present, were collected fromcondemned livers of various livestock. The Echinococcus tapeworm species wasidentified using a multiplex PCR for E. multilocularis, E. granulosus and E. canadensis.Results: E. multilocularis was detected in 6,9 % of golden jackals (7/101) and one pigliver (1/31). In terms of geographical distribution, E. multilocularis was detected nearBelgrade (Ub and Donji Tovarnik), Čajetina, Svilajnac (Grabovac), Požarevac (Ljubinje)and Niš (Vinik).Conclusion: In Serbia, golden jackals are major reservoirs of E. multilocularis and theirpresence near towns and major cities should be regarded as a concern to public health.M3419719

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    BIOREpository (Faculty of Biology, University of Belgrade)
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