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26. Inhibitor selectivity of CNTs and ENTs

Author

Vaskó B, Juhász V, Tóth B, Kurunczi A, Fekete Z, Zolnerciks JK, Kis E, Magnan R, Bidon-Chanal Badia A, Pastor-Anglada M, Hazai E, Bikadi Z, Fülöp F, and Krajcsi P

Subjects
Concentrative nucleoside transporter, IC value, antiviral drug, chemotherapy drug, equilibrative nucleoside transporter, nucleoside analog
Abstract

The concentrative nucleoside transporters (CNT; solute carrier family 28 (SLC28)) and the equilibrative nucleoside transporters (ENT; solute carrier family 29 (SLC29)) are important therapeutic targets but may also mediate toxicity or adverse events. To explore the relative role of the base and the monosaccharide moiety in inhibitor selectivity we selected compounds that either harbor an arabinose moiety or a cytosine moiety, as these groups had several commercially available drug members. The screening data showed that more compounds harboring a cytosine moiety displayed potent interactions with the CNTs than compounds harboring the arabinose moiety. In contrast, ENTs showed a preference for compounds with an arabinose moiety. The correlation between CNT1 and CNT3 was good as five of six compounds displayed IC 50 values within the threefold threshold and one displayed a borderline 4-fold difference. For CNT1 and CNT2 as well as for CNT2 and CNT3 only two of six IC 50 values correlated and one displayed a borderline 4-fold difference. Interestingly, of the six compounds that potently interacted with both ENT1 and ENT2 only nelarabine displayed selectivity. Our data show differences between inhibitor selectivities of CNTs and ENTs as well as differences within the CNT family members.

Published
2019

28. The Mediating Role of Maladaptive Metacognitive Beliefs between Adverse Childhood Experiences and Trait Anxiety.

Author

Horváth, D., Kovács-Tóth, B., Oláh, B., and Fekete, Z.

Subjects
ADVERSE childhood experiences, STRUCTURAL equation modeling, ANXIETY, METACOGNITION, SELF-consciousness (Awareness), METACOGNITIVE therapy
Abstract

Introduction: Adverse childhood experiences (ACE) have a significant negative impact on health. ACEs lead to more pronounced trait anxiety, among others, which serves as a basis for various mental and somatic symptoms. Recent findings suggest that the fact that individuals with more ACEs also have more maladaptive metacognitive beliefs may contribute to the development of these symptoms. Objectives: We aim to study the possible mediating role of maladaptive metacognitive beliefs, resulting from adverse childhood experiences, on trait anxiety. Methods: Data was collected online, anonymously, in a non-clinical population of adults over 18 years of age. The sample consisted of 304 subjects (84.21 % women, 15.79 % men). The applied questionnaires included a demographic questionnaire, the Adverse Childhood Experiences Questionnaire 10 item version, the Meta-Cognitions Questionnaire, and the Spielberger Trait Anxiety Questionnaire. The system of correlations between the examined variables was explored using structural equation modeling (SEM). The study was carried out with ethical approval and in accordance with the Declaration of Helsinki. Results: Our results confirm that ACEs have a significant impact on all the measured dimensions of maladaptive metacognitive beliefs. The direct effect of ACEs on adult trait anxiety is also significant. The results of the study on indirect effects support the joint mediating role of the five metacognitive dimensions. The strongest significant mediating effect was found for the uncontrollability and dangerousness of negative beliefs about worry. Both the direct and indirect effects of cognitive self-consciousness on adult trait anxiety are negative, which means that the more the cognitive self-consiousness is characteristic of someone, the lower the degree of trait anxiety in adulthood is. Conclusions: Our results confirm the mediating effect of metacognitive beliefs on trait anxiety in the context of adverse childhood experiences, which points to the importance of further research on metacognition among the population that suffered early adversities. One of the limitations of the study roots in online data collection: the examined sample is not representative. Moreover, to extend the results, it is recommended to repeat the study on a clinical population. This would enable us to compare our results with those of the clinical population, which could provide further important results in the field of metacognition and adverse childhood experiences. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Published
2024
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