BIOREpository (Faculty of Biology, University of Belgrade)
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    Impact of Skin Exposure to Benzo[a]pyrene in Rat Model: Insights into Epidermal Cell Function and Draining Lymph Node Cell Response

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    The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin's reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin's response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.M214.98631251

    Characterization of peltate trichomes of commercially important Lamiaceae species grown in Serbia

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    Peltate trichomes have been the focus of botanical research for decades as the main secretory structures responsible for the production of essential oil and other specialized metabolites. For this study, samples of the plant material were obtained from the collection of the Institute for Medicinal Plant Research “Dr. Josif Pančić”. This study was conducted to perform morphological characterization, determination of the diameter and analysis of the distribution of peltate trichomes on leaves and calyces of selected commercial Lamiaceae species. In addition, the density of peltate trichomes on the leaves was determined. The analyses were carried out using a stereomicroscope and a scanning electron microscope. The leaves of all plant species bear peltate trichomes on the adaxial and abaxial leaf sides, with the highest density observed in Origanum heracleoticum (24.3 and 17.4 per mm2, re­spectively). Density was generally higher on the adaxial surface, with the exception of Mentha × piperita (higher density on the abaxial side) and Satureja montana (equal density on both leaf sides). The largest diameter of peltate trichomes was observed in leaves and calyces of S. montana (88.79 μm and 90.57 μm, respectively), while the smallest diameter was noticed in Origanum vulgare (about 65.00 μm). The plant species studied differ in appearance, diameter, distribution and density of the peltate trichomes. The results obtained indicate that micromorphological features could be valid parameters for the microscopic authentication of aromatic plants of which the representatives of the Lamiaceae are of par­ticular commercial importance.M5171614

    Cutibacterium acnes as an overseen autoimmunity trigger: Unearthing heat-shock driven molecular mimicry

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    Cutibacterium acnes, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of C. acnes-induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans via molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized C. acnes proteome was performed. The protocol included homology screening between the C. acnes and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of C. acnes mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between C. acnes and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of C. acnes in the pathogenesis of autoimmunity in humans.M215.810542

    Diagnostic properties of miR-146a-5p from liquid biopsies in prostate cancer: A meta-analysis

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    Several studies on biomarker properties of microRNAs from liquid biopsy in prostate cancer (PCa) identified miR-146a-5p as a potential novel diagnostic marker. However, other studies with the same or similar topic failed to confirm the supposed discriminatory ability of miR-146a-5p, for which reason we aimed at elucidating the potential biomarker role of circulatory/urinary miR-146a-5p in PCa by conducting a qualitative and quantitative data synthesis.M222.915552226

    Our Journey from Individual Efforts to Nationwide Support: Implementing Newborn Screening for Spinal Muscular Atrophy in Serbia

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    Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening assay, collaboration with patient organizations and medical professionals, a feasibility study, and negotiation with public health representatives. Over 12,000 newborns were tested during the 17-month feasibility study, revealing two unrelated SMA infants and one older sibling. All three children received therapeutic interventions during the presymptomatic phase and have shown no signs of SMA. No false-negative results were found among the negative test results. As frontrunners in this field in Serbia, we established screening and diagnostic algorithms and follow-up protocols and raised awareness among stakeholders about the importance of early disease detection, leading to the incorporation of NBS for SMA into the national program on 15 September 2023. Since then, 54,393 newborns have been tested, identifying six SMA cases and enabling timely treatment. Our study demonstrates that effective collaborations between academia, non-profit organizations, and industry are crucial in bringing innovative healthcare initiatives to fruition, and highlights the potential of NBS to revolutionize healthcare outcomes for presymptomatic SMA infants and their families.M21a4.05710

    Tritrophic associations and identification key for European species of the genus Binodoxys (Mackauer) (Hymenoptera: Braconidae: Aphidiinae)

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    The genus Binodoxys includes only nine species found in Europe, yet despite its frequent occurrence, it remains insufficiently studied. This study addresses this knowledge gap through an exhaustive literature review and material collection, and a compilation of a comprehensive list detailing tritrophic associations. Based on the available molecular data, we constructed a maximum likelihood tree and a TSC (‘Statistical Parsimony’) haplotype network for six European species. Several new hosts were identified for the first time, and the geographical distribution of one species was broadened. An identification key for females of European Binodoxys species is provided. Future studies should prioritize gathering host data and investigate the existence of cryptic species among polyphagous species. Furthermore, the status of the three species not analyzed in this study due to the lack of material should be investigated by encompassing both morphological and molecular approaches.M230.828130176

    New Insight on the Presence of Several Freshwater Gastropod Species Considered Rare in Serbia

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    The freshwater gastropod fauna of Serbia can be considered understudied compared to the neighbouring countries. This is especially true for the species that frequently occur in smaller and transient habitats such as Aplexa hypnorum (Linnaeus, 1758), Physa fontinalis (Linnaeus, 1758), Anisus (Disculifer) vorticulus (Troschel, 1834), Hippeutis complanatus (Linnaeus, 1758) and Segmentina nitida (O.F. Müller, 1774). Our survey of various smaller habitats in the Pannonian part of Serbia took place in 2021 and 2022 and included 11 sites. One or more of the above-mentioned snail species were found at nine of these sites. Of particular interest are the findings of A. hypnorum, the species whose last and only confirmed finding dated back to the beginning of the 20th century. In total, we present three new localities of A. hypnorum and S. nitida. The number of known localities of A. vorticulus and H. complanatus has doubled (now seven and eight localities respectively). Physa fontinalis, a native species once quite common in the Pannonian areas, is with a declining frequency. During our survey, an abundant population of P. fontinalis was found at a new site. The results presented suggest that a comprehensive survey focusing on smaller and neglected habitats is necessary to fill the gaps in our knowledge of the occurrence and distribution of the freshwater gastropod fauna in Serbia.M230,4434878

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