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1.
Exploring BPA alternatives : environmental levels and toxicity review
Ondrej Adamovsky, Ksenia J Groh, Anna Białk-Bielińska, Beate I. Escher, R. Beaudouin, Liadys Mora Lagares, K. E. Tollefsen, Alja Štern, Tina Eleršek, Marjan Vračko, Bojana Žegura, 2024, pregledni znanstveni članek

Povzetek: Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.
Ključne besede: BPA alternatives, biological activity, in silico, invertebrates, vertebrates, toxicity
Objavljeno v DiRROS: 03.06.2024; Ogledov: 118; Prenosov: 69
.pdf Celotno besedilo (1,64 MB)
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2.
Nature-inspired substituted 3-(imidazol-2-yl) morpholines targeting human topoisomerase IIα : dynophore-derived discovery
Barbara Herlah, Matej Janežič, Iza Ogris, Simona Golič Grdadolnik, Katja Kološa, Sonja Žabkar, Bojana Žegura, Andrej Perdih, 2024, izvirni znanstveni članek

Povzetek: The molecular nanomachine, human DNA topoisomerase IIα, plays a crucial role in replication, transcription, and recombination by catalyzing topological changes in the DNA, rendering it an optimal target for cancer chemotherapy. Current clinical topoisomerase II poisons often cause secondary tumors as side effects due to the accumulation of double-strand breaks in the DNA, spurring the development of catalytic inhibitors. Here, we used a dynamic pharmacophore approach to develop catalytic inhibitors targeting the ATP binding site of human DNA topoisomerase IIα. Our screening of a library of nature-inspired compounds led to the discovery of a class of 3-(imidazol-2-yl) morpholines as potent catalytic inhibitors that bind to the ATPase domain. Further experimental and computational studies identified hit compound 17, which exhibited selectivity against the human DNA topoisomerase IIα versus human protein kinases, cytotoxicity against several human cancer cells, and did not induce DNA double-strand breaks, making it distinct from clinical topoisomerase II poisons. This study integrates an innovative natural product-inspired chemistry and successful implementation of a molecular design strategy that incorporates a dynamic component of ligand-target molecular recognition, with comprehensive experimental characterization leading to hit compounds with potential impact on the development of more efficient chemotherapies.
Ključne besede: topoisomerase II, catalytic inhibitors, chemotherapy, DNA damage, cancer
Objavljeno v DiRROS: 03.06.2024; Ogledov: 194; Prenosov: 72
.pdf Celotno besedilo (7,99 MB)
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3.
Incidence of positive peritoneal cytology in patients with endometrial carcinoma after hysteroscopy vs. dilatation and curettage
Andraž Dovnik, Bojana Crnobrnja, Branka Žegura Andrić, Iztok Takač, Maja Pakiž, 2017, izvirni znanstveni članek

Povzetek: Background. The aim of the study was to compare the frequency of positive peritoneal washings in endometrial cancer patients after either hysteroscopy (HSC) or dilatation and curettage (D&C). Patients and methods. We performed a retrospective analysis of 227 patients who underwent either HSC (N = 144) or D&C (N = 83) and were diagnosed with endometrial carcinoma at the University Medical Centre Maribor between January 2008 and December 2014. The incidence of positive peritoneal cytology was evaluated in each group. Results. There was no overall difference in the incidence of positive peritoneal washings after HSC or D&C (HSC = 13.2%; D&C = 12.0%; p = 0.803). However, a detailed analysis of stage I disease revealed significantly higher rates of positive peritoneal washings in the HSC group (HSC = 12.8%; D&C = 3.4%; p = 0.046). Among these patients, there was no difference between both groups considering histologic type (chi-square = 0.059; p = 0.807), tumour differentiation (chi-square = 3.709; p = 0.156), the time between diagnosis and operation (t = 0.930; p = 0.357), and myometrial invasion (chi-square = 5.073; p = 0.079). Conclusions. Although the diagnostic procedure did not influence the overall incidence of positive peritoneal washings, HSC was associated with a significantly higher rate of positive peritoneal cytology in stage I endometrial carcinoma compared to D&C.
Objavljeno v DiRROS: 03.06.2024; Ogledov: 84; Prenosov: 49
.pdf Celotno besedilo (440,74 KB)
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4.
Genotoxicity and heating performance of VxFe3-xO4 nanoparticles in health applications
Beatriz Sanz-Sagué, Amaia Sáenz-Hernández, Bojana Žegura, Alja Štern, Katja Kološa, Iza Rozman, 2024, izvirni znanstveni članek

Povzetek: The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2O4) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of VxFe3-xO4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V2+ and V3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H0 = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects—types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application.
Ključne besede: magnetic nanoparticles, vanadium ferrite, cytotoxicity, genotoxicity, specific power absorption, cell viability
Objavljeno v DiRROS: 23.05.2024; Ogledov: 118; Prenosov: 120
.pdf Celotno besedilo (8,91 MB)
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5.
Perioperative increase in neutrophil CD64 expression is an indicator for intra-abdominal infection after colorectal cancer surgery
Milena Kerin-Povšič, Bojana Beović, Alojz Ihan, 2017, izvirni znanstveni članek

Povzetek: Colorectal surgery is associated with a high incidence of postoperative infections. Early clinical signs are difficult to distinguish from the systemic inflammatory response related to surgical trauma. Timely diagnosis may significantly improve the outcome. The objective of this study was to compare a new biomarker index CD64 for neutrophils (iCD64n) with standard biomarkers, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP) and procalcitonin (PCT) for the early detection of postoperative infection. Methods. The prospective study included 200 consecutive patients with elective colorectal cancer surgery. Postoperative values of biomarkers from the postoperative day (POD) 1 to POD5 were analysed by the receiver operating characteristic (ROC) analysis to predict infection. The Cox regression model and the Kaplan-Meier method were used to assess prognostic factors and survival. Results. The increase of index CD64n (iCD64n) after surgery, expressed as the ratio iCD64n after/before surgery was a better predictor of infection than its absolute value. The best 30-day predictors of all infections were CRP on POD4 (AUC 0.72, 99% CI 0.61%0.83) and NLR on POD5 (AUC 0.69, 99% CI 0.57%0.80). The best 15-day predictors of organ/ space surgical site infection (SSI) were the ratio iCD64n on POD1 (AUC 0.72, 99% CI 0.58%0.86), POD3 (AUC 0.73, 99% CI 0.59%0.87) and CRP on POD3 (AUC 0.72, 99% CI 0.57%0.86), POD4 (AUC 0.79, 99% CI 0.64%0.93). In a multivariate analysis independent risk factors for infections were duration of surgery and perioperative transfusion while the infection itself was identified as a risk factor for a worse long-term survival. Conclusions. The ratio iCD64n on POD1 is the best early predictor of intra-abdominal infection after colorectal cancer surgery. CRP predicts the infection with the same predictive value on POD3.
Ključne besede: colorectal surgery, index CD64n, postoperative infection
Objavljeno v DiRROS: 10.05.2024; Ogledov: 178; Prenosov: 67
.pdf Celotno besedilo (666,38 KB)

6.
Development and preliminary validation of the scale of factors which influence decision-making of the elderly to take part in physical exercise programs
Tatjana Tomažič, Bojana Filej, Nadja Plazar, 2023, izvirni znanstveni članek

Povzetek: Regular physical activity and exercise are beneficial for both physical and mental health. However, in the elderly, the level of physical activity they partake in is consist-ently inadequate. Recognizing the need to enhance the participation of the elderly in organized physical exercise and understanding the factors which influence their deci-sion-making becomes pivotal. The purpose of this study was to develop a measurement instrument, specifically a scale, to identify these factors and evaluate its psychometric properties. First, the statements were formulated, which was followed by content as-sessment by a panel of experts. In the process of scale validation, its internal consist-ency, stability, correlations between the variables, and factor structure were also evalu-ated. The scale was tested on a sample of 1777 participants engaged in guided physical exercise at the School of Health Association (društvo Šola zdravja), all aged 60 years or more. Theexploratory factor analysis yielded a four-factor model with 27 state-ments which explained 42.9% of variability. The results indicated weak, but statistically significant correlations between the factors and an acceptable level of internal consist-ency and stability of the entire scale. This scale, developed to establish the factors that influence the decision-making of the elderly to take part in organized physical exercise, represents a valid and reliable measurement instrument, which can be beneficial in the planning and promotion of organized physical exercise programs for the elderly.
Ključne besede: physical exercise, quantitative methodology, elderly, social gerontology
Objavljeno v DiRROS: 16.04.2024; Ogledov: 155; Prenosov: 122
.pdf Celotno besedilo (610,88 KB)
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7.
Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell lines
Matija Rojnik, Zala Jevnikar, Bojana Mirković, Damjan Janeš, Nace Zidar, Danijel Kikelj, Janko Kos, 2011, izvirni znanstveni članek

Povzetek: Background. Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods. BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results. In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions. Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression.
Objavljeno v DiRROS: 18.03.2024; Ogledov: 319; Prenosov: 293
.pdf Celotno besedilo (722,81 KB)
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8.
Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell lines
Matija Rojnik, Zala Jevnikar, Bojana Mirković, Damjan Janeš, Nace Zidar, Danijel Kikelj, Janko Kos, 2011, izvirni znanstveni članek

Povzetek: Background. Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods. BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results. In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions. Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression.
Objavljeno v DiRROS: 18.03.2024; Ogledov: 204; Prenosov: 39
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9.
Subchronic exposure of rats to sublethal dose of microcystin-YR induces DNA damage in multiple organs
Metka Filipič, Bojana Žegura, Bojan Sedmak, Irena Horvat-Žnidaršič, Aleksandra Milutinović Živin, Dušan Šuput, 2007, izvirni znanstveni članek

Povzetek: Background. Microcystins (MCs) are cyclic heptapeptides that are considered tobe liver specific toxins. They are potent tumour promoters and recent studies indicate that they are also genotoxic. In this study we measured DNA damage in lymphocytes, liver, kidney (cortex and medulla), lung, spleen and brain cells of male Fisher F344 rats that were exposed to sublethal dose (every second day 10 Ugžkg b.w.č i.p) of microeysrin-YR (MCYR) for one month. Methods. At the end of exposure the animals were sacrificed, the lymphocytes were isolated from blood taken from jugular vein, liver cells were obtained byperfusion with collagenase A and the cells from other organs were isolated by incubating small tissue pieces with eollagenase A. The DNA damage in isolated cells was measured with the single cells gel electrophoresis (SCGE) also called the comet assay. Results. A significant increase of the % tail DNAin MCYR-exposed animals compared to the nonexposed control ones was observed in brain (2.5 fold), liver (2.1 fold), kidney medulla (1.9 fold), kidney cortex (1.8 fold) and lung (1.7 fold) cells, while the DNA from lymphocytes and spleen cells was not affected. Conclusion. This study demonstrated that subehronic exposure to sublethal doses of MCs can induce systemicgenotoxicity in mammals, and it affects not only the liver but also other vital organs.
Ključne besede: DNA damage, comet assay, cyanobacteria, bacterial toxins, rats, inbred F344
Objavljeno v DiRROS: 20.02.2024; Ogledov: 233; Prenosov: 55
.pdf Celotno besedilo (142,90 KB)

10.
Cerebral hyperperfusion syndrome after carotid angioplasty
Zoran Miloševič, Bojana Žvan, Marjan Zaletel, Miloš Šurlan, 2002, objavljeni znanstveni prispevek na konferenci

Povzetek: Background. Cerebral hyperperfusion syndrome after carotid endarterectomy is an uncommon but well-de- fined entity. There are only few reports of "hyperperfusion injury" following carotid angioplasty. Case report. We report an unstable arterial hypertension and high grade carotid stenosis in a 58-year-old, right-handed woman. After a stroke in the territory of middle cerebral artery carotid angioplasty was per- formed in the patient. Among riskfactors, the long lasting arterial hypertension was the most pronounced. Immediately after the procedure, the patient was stable without any additionalneurologic deficit. The sec- ond day, the patient had an epileptic seizure and CT revealed a small haemorrhage in the left frontal lobe. Conclusions. The combination of a high grade carotid stenosis and unstable arterial pressure is probably an important prognostic factor in the pathogenesis of hyperperfusion syndrome.
Objavljeno v DiRROS: 31.01.2024; Ogledov: 213; Prenosov: 61
.pdf Celotno besedilo (347,68 KB)

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