91. ACE gene and male infertility : a South Slavic case-control study and multi-omics data integrationTanja Kunej, Rebeka Podgrajšek, Helena Jaklič, Alenka Hodžić, Martin Štimpfel, Olivera Miljanović, Momčilo Ristanović, Ivana Novaković, Dijana Plašeska Karanfilska, Predrag Noveski, Saša Ostojić, Alena Buretić-Tomljanović, Antun Gršković, Borut Peterlin, 2025, original scientific article Abstract: Components of the renin-angiotensin system (RAS) are expressed in both female and male reproductive tracts, with angiotensin I converting enzyme (ACE) being an important component for male reproductive function, as shown in animal models. The most studied ACE polymorphism is the Alu insertion-deletion (I/D), which has been proposed to have a negative effect on male fertility. Given the conflicting evidence in the literature, we conducted a multicentric case-control study to investigate the association between the ACE Alu I/D polymorphism and impaired spermatogenesis. Using PCR amplification and agarose electrophoresis, we genotyped the ACE gene Alu I/D polymorphism in 745 South Slavic men. The study group consisted of 457 patients with impaired spermatogenesis, 239 with non-obstructive azoospermia (NOA) and 218 with oligoasthenoteratozoospermia (OAT) and a control group of 288 fertile men. No association was found between the Alu I/D polymorphism and these semen phenotypes, suggesting that it is not associated with NOA or severe OAT in this cohort. To provide a broader regulatory context, we also developed an integrative atlas of ACE regulatory elements by in silico multi-omics analysis using genomics databases and bioinformatics tools. Data integration revealed various regulatory mechanisms at multiple omics levels, including genomics, epigenomics, miRNAomics, transcriptomics, proteomics and epiproteomics. These include genomic variants with predicted deleterious effects, a CpG island, microRNAs (miRNAs) and post-translational modifications (PTMs). In addition, protein interaction analysis revealed that ACE is indirectly linked to several proteins previously associated with male infertility and is also targeted by miRNA previously associated with oligozoospermia. This comprehensive, multi-faceted approach, combining genetic association analysis with bioinformatics, provides insights into ACE regulation in its broader molecular context. These results emphasize the importance of further integrative multi-omics and systems biology research to better understand the role of ACE in male reproductive function.
Keywords: angiotensin I converting enzyme (ACE), male infertility, azoospermia, oligozoospermia, multi-omics
Published in DiRROS: 09.12.2025; Views: 80; Downloads: 33
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92. Risking public health by approving some health claims? : The case of phosphorusIgor Pravst, 2011, other scientific articles Abstract: There is a well-established consensus on the many biological functions of essential nutrients, and related general function health claims will be soon authorised in the European Union. Such claims about the role of nutrients in the body`s growth, development and functioning could provide a powerful marketing tool and signi?cant increase in the consumption of specific food products. Even though these claims are scientifically substantiated, there are both health and ethical concerns about whether such claims should be allowed where the intake of these nutrients easily exceeds the recommendations and a bigger intake might have adverse affects. The case of phosphorus and its role in the maintenance of normal bone is discussed.
Keywords: health claims, consumer protection, essential nutrients, adverse effects
Published in DiRROS: 09.12.2025; Views: 77; Downloads: 41
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96. European human granulocytic anaplasmosis is caused by a subcluster of Anaplasma phagocytophilum Ecotype IPaulina M. Lesiczka, Friederike D. von Loewenich, Robert Kohl, Aleksandra I. Krawczyk, Ron P. Dirks, Pierre H. Boyer, Benoit Jaulhac, Anna Moniuszko-Malinowska, Tina Uršič, Franc Strle, Stanka Lotrič-Furlan, Tatjana Avšič-Županc, Miroslav Petrovec, Hein Sprong, 2025, original scientific article Abstract: Anaplasma phagocytophilum causes human granulocytic anaplasmosis. However, despite its ubiquitous presence in animals and ticks, human cases are rarely reported in Europe. We generated genetic data from A. phagocytophilum from patients and compared them with sequences from wild and domestic animals to assess the zoonotic potential of the respective genotypes. The genomic sequence of an A. phagocytophilum isolate obtained from a Slovenian patient was determined. We also sequenced a groEL-gene fragment of eight isolates from human patients from France and Poland. The A. phagocytophilum genome from the Slovenian patient was more closely related to isolates from dogs than from sheep. Using groEL-based typing, isolates from humans were found within a distinct subcluster of A. phagocytophilum Ecotype I. This subcluster was defined as zoonotic. Strains from dogs, horses, cats, foxes, wolves, and wild boar were significantly overrepresented in this branch. Variants outside this subcluster were more abundant and found in a wider variety of domestic and wild animals, most notably ruminants. A similar pattern was observed for the MLST analyses targeting seven housekeeping genes. Human anaplasmosis in Europe is associated with a specific subcluster of A. phagocytophilum Ecotype I, which is not primarily associated with ruminants, but rather with dogs, horses, cats, carnivores, wild boar and hedgehogs. Our findings provide a reasonable explanation for the discrepancy between the omnipresence of A. phagocytophilum in the environment and the limited number of reported human cases. We recommend taking this genetic sub-clustering into account for future risk assessments.
Keywords: Anaplasma phagocytophilum, groEL, human granulocytic anaplasmosis, Ixodes ricinus, multilocus sequence typing, ecotypes, whole genome sequence, ticks
Published in DiRROS: 09.12.2025; Views: 56; Downloads: 30
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99. Anticoagulant management in an antithrombin-deficient pregnant woman with a history of venous thromboembolism : a case reportMatija Kozak, Tjaša Vižintin Cuderman, Mojca Božič Mijovski, Miha Lučovnik, Marko Miklič, Gregor Tratar, Tamara Rojnik, 2025, other scientific articles Abstract: Background: Antithrombin deficiency (ATD) in pregnant patients significantly increases the risk of venous thromboembolism (VTE), but guidelines for managing anticoagulation during pregnancy, labour, and postpartum in patients with ATD are limited. Case presentation: A pregnant woman with ATD suffered recurrent VTE in the 20th week of pregnancy despite therapeutic doses of low-molecular-weight heparin (LMWH). The acute VTE was treated with argatroban and then with warfarin until delivery. LMWH with antithrombin (AT) concentrate was introduced before and shortly after delivery, followed by warfarin, which was continued also postpartum. No further complications occurred during the remainder of pregnancy, delivery, and two-year follow-up. Conclusion: Our case highlights the challenges of anticoagulant treatment in pregnant patients with ATD. Standard weight-based LMWH dosing can lead to inadequate anticoagulation, as demonstrated by an acute VTE event in our patient. In our case, the use of argatroban proved to be safe and effective in the acute setting, followed by warfarin in the 2nd and 3rd trimester, and subsequent co-administration of LMWH and AT concentrate before and after delivery. Concomitant use of LMWH and AT concentrate allows for achieving target anti-Xa levels. Measurement of both anti-Xa and AT activity is advisable in this scenario to ensure reliable anticoagulant management. ATD is a heterogeneous disorder; therefore, each successfully managed pregnancy advances clinical practice.
Keywords: anticoagulants, antithrombin III, case report, pregnancy, venous thromboembolism
Published in DiRROS: 09.12.2025; Views: 99; Downloads: 45
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100. Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadismNadan Gregorič, Jaka Šikonja, Andrej Janež, Mojca Jensterle Sever, 2025, original scientific article Abstract: Aims To compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and parameters of functional hypogonadism (FH) in men with type 2 diabetes mellitus and obesity. Materials and Methods We designed a randomised open-label trial in 25 men with type 2 diabetes (aged 50 [46–60] years, BMI 35.9 [32.8–38.7] kg/m2) and FH randomised to semaglutide (SEMA) 1 mg/week or intramuscular testosterone undecanoate (TRT) 1000 mg/10–12 weeks for 24 weeks. Semen analysis and parameters of FH were measured at baseline and after 24 weeks of treatment. Participants completed questionnaires of the International Index of Erectile Function-15 (IIEF-15) and the Aging Symptoms in Men (AMS). Results The quality of baseline sperm parameters of our study cohort was poor, below the 5th percentile of reference values. In the SEMA group, there was a significant increase in morphologically normal sperm from baseline to the end of the study (2% [2; 3.5] vs. 4% [2; 5.5]; p = 0.012), whereas sperm concentration and total number decreased significantly in the TRT group. Compared to TRT, the SEMA group had a significantly higher number of morphologically normal sperm, sperm concentration and total number. Both groups experienced an increase in total testosterone and improvement in the AMS score, whereas the IIEF-15 score significantly improved only in the TRT group. Conclusion Semaglutide markedly improved sperm morphology, total testosterone levels and symptoms of hypogonadism. These findings highlight semaglutide's potential as a therapeutic approach for men with obesity-related FH who desire fertility.
Keywords: functional hypogonadism, obesity, semaglutide
Published in DiRROS: 09.12.2025; Views: 58; Downloads: 26
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