BIOREpository (Faculty of Biology, University of Belgrade)
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    Molecular Detection and Genetic Variability of Hepatozoon canis in Golden Jackals (Canis aureus L. 1758) in Serbia

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    Hepatozoon canis is a protozoan tick-borne parasite infecting domestic and wild canids, including foxes, wolves, and jackals. It is mainly found in dogs but has also been detected in several wild carnivores, including foxes, wolves, and jackals. Host transmission primarily occurs through the ingestion of infected ticks, typically Rhipicephalus sanguineus, with documented instances of transplacental transmission from infected females to cubs. In Serbia, the golden jackal is common throughout the country, and its population has increased in recent years. Previous research has documented the presence of several vector-borne pathogens in the jackal population in Serbia, so we conducted this study to determine the presence, prevalence, and genetic variability of H. canis. Over eleven years (2010-2020), 114 animal samples were collected from 23 localities in Serbia. A total of 90/114 (78.95%) jackals were positive for H. canis, and they came from 22 localities. Among 15 juveniles, almost half (6/15 (40%)) tested positive for H. canis. In addition to the high prevalence, high genetic variability of the pathogen was also found. According to the mutated positions, four sequence types (S4-S7) of H. canis were determined. Based on our earlier research on the grey wolf and on this study, it can be observed that various sequence types of H. canis circulate within wild canid populations in Serbia. The prevalence of H. canis infection in wild carnivores raises significant concerns for wildlife conservation and animal health. Infected animals may act as reservoirs for the disease, posing a potential risk to domestic animals by acting as a source of infection.41113

    Trends in Anti-Tumor Effects of Pseudomonas aeruginosa Mannose-Sensitive-Hemagglutinin (PA-MSHA): An Overview of Positive and Negative Effects

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    Cancer is a leading cause of death worldwide, for which finding the optimal therapy remains an ongoing challenge. Drug resistance, toxic side effects, and a lack of specificity pose significant difficulties in traditional cancer treatments, leading to suboptimal clinical outcomes and high mortality rates among cancer patients. The need for alternative therapies is crucial, especially for those resistant to conventional methods like chemotherapy and radiotherapy or for patients where surgery is not possible. Over the past decade, a novel approach known as bacteria-mediated cancer therapy has emerged, offering potential solutions to the limitations of conventional treatments. An increasing number of in vitro and in vivo studies suggest that the subtype of highly virulent Pseudomonas aeruginosa bacterium called Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) can successfully inhibit the progression of various cancer types, such as breast, lung, and bladder cancer, as well as hepatocellular carcinoma. PA-MSHA inhibits the growth and proliferation of tumor cells and induces their apoptosis. Proposed mechanisms of action include cell-cycle arrest and activation of pro-apoptotic pathways regulated by caspase-9 and caspase-3. Moreover, clinical studies have shown that PA-MSHA improved the effectiveness of chemotherapy and promoted the activation of the immune response in cancer patients without causing severe side effects. Reported adverse reactions were fever, skin irritation, and pain, attributed to the overactivation of the immune response. This review aims to summarize the current knowledge obtained from in vitro, in vivo, and clinical studies available at PubMed, Google Scholar, and ClinicalTrials.gov regarding the use of PA-MSHA in cancer treatment in order to further elucidate its pharmacological and toxicological properties.M214,552416

    In silico analysis of the impact of toxic metals on COVID-19 complications: molecular insights

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    COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.M221,710210975

    Integrated mathematical modeling, experimental and bioinformatics study of Type-II antitoxin-toxin system's response to antibiotic exposure

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    M3442

    Carpinus austrobalcanica – A new highly polyploid species from the Balkan Peninsula closely related to European hornbeam

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    The Balkan Peninsula was the primary glacial refugium for many temperate tree species and contributed overproportionally to the postglacial recolonisation of central and eastern Europe. This is also the case for Carpinus betulus, the European hornbeam, whose main glacial refugium was in the Balkans. During our fieldwork in the southern Balkans, we discovered trees with a morphology similar to that of C. betulus, but differing in their rough, highly rigged bark and the shape of their fruit involucre. The aim of this study was to investigate the evolutionary origin and differentiation of these morphologically distinct populations of C. betulus from the North Pindus Mountain range in northern Greece and southern Albania using an integrative approach. Our study combined phylogenetic analyses of plastid and nuclear internal transcribed spacer sequences, amplified fragment length polymorphism fingerprinting, relative genome size estimation, and multivariate morphometric analyses. After establishing the genetic and morphological divergence of the aforementioned populations, we described them as a new species, Carpinus austrobalcanica D.Lakušić, Kuzmanović, Stevanoski, Schönsw. & Frajman, sp. nov. We provide diagnosis, description, geographical distribution, and conservation status of this enigmatic newly described tree species locally endemic to the southern Balkans.M213.61258126

    Antiferroptotic effect of hydrogen-sulfide donors on the pancreas and liver in type 1 diabetic mice

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    The pathogenesis of diabetes mellitus (DM) involves progressive cell death in islets and diabetes-targeted tissues. Ferroptosis, an iron-driven form of programmed cell death, has emerged as an important antidiabetic target. DM is also associated with decreased systemic and peripheral hydrogen sulfide (H2S) levels that contribute to DM pathology. Although recent findings indicate that H2S protects cells from ferroptosis, its role in DM prevention/amelioration is not elucidated. Thus, we aimed to examine the anti-ferroptotic potential of the donors of H2S and its reactive species on pancreas and early stages liver pathology in diabetic mice. DM was induced in C57BL/6 mice with streptozotocin (STZ, 65 mg/kg/day for 3 days). Synthetic H2S donors (1) GYY4137, (2) sodium sulfide (Na2S4) and (3) cysteine-3-sulfide (Cys-S3) were administered intraperitoneally, starting with the first dose of STZ for 3 weeks. Histologic examinations of the pancreas and liver and immunohistochemical analyses of insulin, 4-hydroxynonenal (4HNE) and glutathione (GSH) peroxidase 4 (GPX4) were performed. The GSH level and antioxidative enzymes activities were measured spectrophotometrically. The levels of ferroportin (FPN), ferritin (FTH) and ACSL4 were analysed by Western blot. The level of heme oxygenase- 1 (HO-1) was measured by ELISA. The results suggest that treatment with H2S donors, particularly Cys-S3, prevents the development of DM, as evidenced by lower glucose levels and DM incidence compared to untreated diabetic mice. In the pancreas, treatment with H2S donors improved the overall morphology, islet size, insulin and GPX4 expression in the islets and the amount of GSH. In the liver of diabetic mice early pro-ferroptotic phenotype seen through ferroptosis markers: increased content of free iron and lipid peroxidation product, 4HNE and expression of the main ferroptosis driver - ACSL4 were reduced with H2S donors. H2S donors also restored the expression of the iron- regulatory proteins FPN1 and FTH1, HO-1, and the activity of GSH-S-transferase and catalase. The beneficial effects of the H2S donors, particularly Cys-S3, were also evident in improved overall liver appearance, reduced fibrosis and an increased amount of binucleated hepatocytes. These data clearly show the strong antiferroptotic potential of H2S donors and suggest a new approach for the prevention/treatment of diabetes and diabetic diseases based on targeting ferroptosis via H2S signalling.M3421

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