601. Bisphenol a disrupts steroidogenesis and induces apoptosis in human granulosa cells cultured in vitroDominika Celar Šturm, Tadeja Režen, Nina Jančar, Irma Virant-Klun, 2025, izvirni znanstveni članek Povzetek: Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 µM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 µM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 µM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations.
Ključne besede: bisphenol A, human granulosa cells, steroidogenesis, apoptosis, steroid hormones
Objavljeno v DiRROS: 13.11.2025; Ogledov: 163; Prenosov: 72
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602. Safety, long-term effectiveness, and immunogenicity of varicella vaccination in children with juvenile idiopathic arthritis treated with biologic therapyMaša Bizjak, Jakob Peterlin, Tadej Avčin, Miroslav Petrovec, Alojz Ihan, Mojca Zajc Avramovič, Gašper Markelj, Tina Vesel, Veronika Osterman, Jerneja Ahčan, Helena Mole, Katja Dejak Gornik, Alenka Biteznik, Sara Jevnikar, Larisa Janžič, Miha Bajc, Andreja Nataša Kopitar, Nataša Toplak, 2025, izvirni znanstveni članek Povzetek: Objective: To evaluate safety, long-term effectiveness and immunogenicity of varicella vaccination in children with JIA, treated with biologic disease-modifying antirheumatic drugs (bDMARDs). Methods: This is a prospective case-control study. VZV-naive patients with JIA on selected bDMARDs (TNFi, IL-6 and IL-1 inhibitors), who were at risk for contracting varicella, had stable disease and normal values of immunoglobulins and lymphocyte populations, were vaccinated against varicella. Adverse events (AEs) and disease activity were followed after vaccination. VZV-specific humoral (VZV-IgG) and cell-mediated immunity (VZV-CMI) were measured at predetermined time points after vaccination by Liaison and intracellular cytokine staining, respectively. Two healthy control (HC) groups comprised 52 healthy children after varicella vaccination and 69 healthy children after varicella infection. Results: 17 patients were vaccinated against varicella (12 on TNFi, 4 on IL-6 inhibitors and 1 on IL-1 inhibitor), of whom 14 patients received both the first and second dose on bDMARDs. No vaccine-strain infections or other serious AEs occurred after vaccination. Disease activity increased in 3/17 (18 %) patients following vaccination. Four out of 17 (24 %) patients developed mild breakthrough varicella (BV) 4 months-4.5 years after vaccination, and none of the HC. Fourteen out of 17 (82 %) patients and 50/52 (96 %) vaccinated HC were seropositive after second vaccination and 8/11 (72 %) patients and 42/43 (98 %) vaccinated HC developed VZV-CMI, which persisted longer compared to VZV-IgG. Patients presented lower antibody levels compared to HC. The rate of VZV-IgG decline was comparable between patients and HC after vaccination or infection. Five patients received the third vaccine dose due to primary or secondary vaccine failure, and none of them developed BV. Conclusions: Varicella vaccination was safe and largely immunogenic in our cohort of JIA patients treated with bDMARDs. Although the vaccination was not always fully effective, it prevented severe disease in all vaccinated patients.
Ključne besede: varicella vaccination, juvenile idiopathic arthritis, biologic therapy, anti-cytokine therapy
Objavljeno v DiRROS: 13.11.2025; Ogledov: 186; Prenosov: 75
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604. Napredno upravljanje betonarn s podporo digitalnih dvojčkovMateja Držečnik, Uroš Klanšek, Tjaša Zupančič Hartner, Rok Cajzek, 2025, pregledni znanstveni članek Povzetek: Članek predstavlja najnovejše stanje tehnike na področju naprednega upravljanja betonarn s podporo digitalnih dvojčkov (angl. Digital Twins, DT), s poudarkom na povezovanju senzorskih podatkov, spremljanju procesov v realnem času, napovednem vzdrževanju, simulacijah delovanja in usposabljanju v kontekstu razvoja Industrije 4.0. Za zagotavljanje ažurnega virtualnega modela betonarne, tj. njenega DT, se kontinuirano zbirajo potrebni podatki iz številnih sistemskih komponent. Računalniška analitika, ki podpira DT betonarne in se napaja s podatki v realnem času, omogoča hitre prilagoditve v proizvodnem procesu, kar izboljšuje učinkovitost in zmanjša količino odpadkov. DT betonarne tako služi tudi kot učinkovito orodje za usposabljanje strokovnjakov, saj omogoča preizkušanje različnih scenarijev brez tveganja za dejanski obrat. Poleg tega DT izboljša preglednost delovanja in predvidljivost vzdrževanja betonarne ter poveča njeno operativno učinkovitost, kar vodi do znižanja stroškov in doseganja višjih nivojev kakovosti poslovanja. Prispevek poudari vlogo DT pri preoblikovanju tradicionalnih proizvodnih procesov, kot je proizvodnja betona, in podaja reprezentativen dejanski primer srednje velike betonarne, ki s podporo DT kaže napredek pri upravljanju tovrstnih proizvodnih obratov.
Ključne besede: betonarne, digitalni dvojčki, industrija 4.0, spremljanje procesov, vzdrževanje, simulacije, usposabljanje
Objavljeno v DiRROS: 13.11.2025; Ogledov: 185; Prenosov: 81
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605. Prophylactic treatment of hepatitis C virus infection after kidney transplantation with the combination of glecaprevir/pibrentasvir and sofosbuvir in a highly sensitized hepatitis c virus-negative recipient : a case report and review of the literatureTanja Belčič Mikič, Igor Sterle, Mojca Matičič, Miha Arnol, 2025, drugi znanstveni članki Povzetek: Background: Since the discovery of successful direct-acting antiviral (DAA) treatment, kidneys from hepatitis C virus (HCV) RNA-positive donors represent a new opportunity to expand the organ donor pool for HCV-negative recipients. Case presentation: In this paper, we describe a unique case of transplantation of an HCV genotype 3a-infected kidney into an HCV-negative recipient who was highly sensitized, with a virtual panel-reactive antibody level of 99.96%. Prior to the kidney transplantation, the recipient received DAA treatment with glecaprevir/pibrentasvir as a viable prophylactic strategy. Post-transplant, the recipient received a triple-combination DAA regimen with glecaprevir/pibrentasvir/sofosbuvir, which continued for 12 weeks. Subsequently, viral load was undetectable at 12 and 24 weeks after treatment, with no significant adverse events associated with DAA therapy. A 12-month post-transplantation biopsy revealed mixed rejection requiring treatment. The 19-month follow-up showed a favorable outcome regarding the function of the kidney allograft and the recipient’s quality of life. HCV-positive transplantation allowed our recipient to receive a kidney from an immunologically compatible donor without donor-specific antibodies and the need for desensitization strategies. Conclusions: Each transplant center should decide on the selection of candidates for kidney transplantation from HCV RNA-positive donors to HCV-negative recipients, the availability and choice of DAA treatment, and post-transplant follow-up. Our case emphasizes the need for early DAA treatment based on viral load and HCV genotyping, as well as for careful post-transplant surveillance including protocol biopsies.
Ključne besede: kidney transplantation, HCV RNA, direct-acting antiviral (DAA), glecaprevir/pibrentasvir, sensitization, case report
Objavljeno v DiRROS: 12.11.2025; Ogledov: 170; Prenosov: 74
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607. Exhausted natural killer cells in adult IgA vasculitisMatija Bajželj, Emanuela Senjor, Nika Boštic, Matjaž Hladnik, Snežna Sodin-Šemrl, Milica Perišić, Janko Kos, Alojz Ihan, Alojzija Hočevar, Andreja Nataša Kopitar, Katja Lakota, 2025, izvirni znanstveni članek Povzetek: Introduction. IgA vasculitis nephritis (IgAVN) manifests in up to 84% of adult patients with IgA vasculitis (IgAV) and is associated with an elevated risk of progression to chronic kidney failure. The underlying pathogenic mechanism of adult IgAVN in leukocytes remain largely uncharacterised. Although natural killer (NK) cells were investigated in paediatric IgAV, their specific role in the pathogenesis of adult IgAV has yet to be elucidated. Methods. RNA sequencing of leukocytes from adult IgAV patients and healthy controls (HC) was performed. NK cells’ cytotoxicity was assessed using calcein-AM stained K562 cells, and exocytosis was measured by LAMP-1/CD107a expression. Intracellular perforin and granzyme B were analyzed via flow cytometry, and cytokine secretion was measured by Luminex xMAP. Interferon-induced genes were validated with qPCR. Results. Principal component analysis (PCA) of leukocyte gene expression profiles distinguished IgAV patients from HC. Pathway enrichment analysis showed differences in patients’ subsets - Interferon signalling Reactome pathway was observed only in sample from patients with skin-limited IgAV (sl-IgAV) and was confirmed by increased expression of interferon-induced genes using qPCR. Only in samples from IgAVN patients enrichment of NK cell-mediated cytotoxicity KEGG pathway was found. NK cells from IgAVN patients showed significantly decreased cytotoxicity compared to samples from sl-IgAV patients (p = 2.53 × 10− 2). The % of CD107a+-NK cells significantly increased after stimulation in HC (p = 9.7 × 10− 3) and in sl-IgAV patient samples (p = 2.21 × 10− 2) while only a minor increase was observed in samples of IgAVN patients. IgAVN patients exhibited a decreased % of perforin+ NK cells compared to HC. Following phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation, a significant reduction in intracellular perforin level was observed in HC (p = 2.53 × 10− 2), but not in IgAVN patients NK cells. Interferon (IFN)-ϒ and macrophage inflammatory protein (MIP)-1β were significantly decreased in NK cell culture supernatants from IgAVN patients (p = 2.64 × 10− 2 and p = 2.65 × 10− 2 respectively). Conclusion. Patients with IgAVN exhibited impaired cytotoxic and immunomodulatory functions of NK cells, along with a marked absence of interferon signaling in PBMCs. Further studies are needed to confirm if discrimination of patient subsets based on leukocyte samples might be of clinical use and if deregulated NK function might contribute to the pathogenesis of nephritis in adult IgAV.
Ključne besede: immunoglobulin A, IgAVN, IgA vasculitis, RNA sequencing, kidney diseases, immunoglobulins, killer cells, adults
Objavljeno v DiRROS: 12.11.2025; Ogledov: 200; Prenosov: 84
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608. Associations of essential and non-essential trace elements’ levels in the blood, serum, and urine in women with premature ovarian insufficiencyTina Kek, Ksenija Geršak, Nataša Karas Kuželički, Dominika Celar Šturm, Darja Mazej, Janja Snoj Tratnik, Ingrid Falnoga, Milena Horvat, Irma Virant-Klun, 2025, izvirni znanstveni članek Povzetek: Premature ovarian insufficiency (POI) is poorly understood, with causes identified in only 25% of cases. Emerging evidence suggests links between trace elements (TEs) and POI. This study is the first to compare concentrations of manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) across urine, serum, and whole blood in women with POI compared to healthy controls (HC), aiming to explore their distribution and potential associations with POI. This cross-sectional-case-control study enrolled 81 participants (40 POI patients and 41 healthy controls) at the University Medical Centre Ljubljana, Slovenia. Blood and urine samples were collected to quantify basic biochemical parameters using standard clinical chemistry methods and concentrations of Mn, Cu, Zn, Se, Mo, As, Cd, Hg, and Pb using inductively coupled plasma-mass spectrometry (ICP-MS). Participants also completed questionnaires on socio-demographics, medical history, lifestyle, and nutrition. Data was analyzed using the Mann–Whitney U test, Student's t-tests, Fisher exact test, logistic regression models adjusted on body mass index (BMI), age, hematocrit, and Kendall's tau correlation. Women with POI had significantly higher BMI and red blood cell (RBC) indices, including hemoglobin, hematocrit, and red cell distribution width (RDW), compared to controls. A larger proportion of POI patients resided in rural agricultural areas. Liver and kidney function assessments showed no significant differences between the groups. Adjusted models revealed that POI patients had significantly lower urinary levels of Cu, Zn, Se, Mo, Cd, Hg, and Pb than controls, while whole blood Mn levels were higher. Serum Cu levels were significantly elevated in POI patients, whereas Pb, Cd, and Hg were lower. No significant differences were observed for As. Correlation analysis showed several strong to moderate associations among TEs across biofluids, but only weak correlations were found between TEs and demographic or biochemical factors. This study suggests potential associations between TEs and POI in women. Notably, most TEs (Zn, Se, Cu, Mo, Cd, Hg, Pb) were significantly lower in the urine of the POI group, while Cu, Cd, Hg, and Pb showed significant differences in both urine and serum.
Ključne besede: premature ovarian insufciency, essential, non-essential trace elements, biofuids, reproductive health
Objavljeno v DiRROS: 12.11.2025; Ogledov: 157; Prenosov: 81
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609. Teriparatide in sequental treatment of osteoporosis in a patient with spinal muscular atrophy : a case report and literature reviewMatej Rakuša, Lea Leonardis, Blaž Koritnik, Andrej Janež, Mojca Jensterle Sever, 2025, drugi znanstveni članki Povzetek: We report the case of a female patient with spinal muscular atrophy type 3c, low bone mineral density and multiple fragility fractures, successfully treated with teriparatide. She sustained a vertebral fracture at age 35 years while treatment naïve, and additionally, one vertebral fracture as well as an intertrochanteric right hip fracture during the 5-year treatment with oral bisphosphonates. A sequential 2-year treatment with teriparatide followed by a one-year treatment with oral bisphosphonate risedronate resulted in an overall 11-year fracture-free period and stable bone mineral density. Teriparatide is an osteoanabolic medication that effectively reduces vertebral and nonvertebral fractures in postmenopausal, male and glucocorticoid-induced osteoporosis, particularly in individuals at very high risk of fracture. In the context of neuromuscular disease, teriparatide proved effective in the treatment of osteoporosis in Duchenne muscular dystrophy. In contrast, the data for patients with spinal muscular atrophy are lacking. Further studies are needed to assess its role in this population.
Ključne besede: spinal muscular atrophy, osteoporosis, fracture
Objavljeno v DiRROS: 12.11.2025; Ogledov: 183; Prenosov: 82
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