Cell Calcium, Год журнала: 2025, Номер unknown, С. 103014 - 103014
Опубликована: Март 1, 2025
Язык: Английский
Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(9), С. 798 - 810
Опубликована: Авг. 9, 2024
Язык: Английский
Процитировано
3
Опубликована: Янв. 7, 2025
<p dir="ltr">Psoriatic arthritis mutilans (PAM) and atopic dermatitis (AD) are two skin disorders. PAM is the most severe rarest form of psoriatic arthritis, it characterized by osteolysis joint erosion, leading to permanent disability. There no clear susceptibility genes identified for PAM. AD, a chronic inflammatory condition, influenced genetic environmental factors, resulting in barrier dysfunction, inflammation, immune dysregulation. In while risk factors have been explained, these explain only modest proportion heritability. The pathogenesis varies different populations, such as those African descent.</p><p dir="ltr">In this thesis, I explore molecular underpinnings both AD through next-generation sequencing functional studies. We aim uncover novel involved disease development. research goals were achieved following four studies included thesis.</p><p study I, we performed Next-generation Nordic cohort (n = 61) basis uncovered rare variants NADPH oxidase 4 (NOX4) gene suggested NOX4 candidate gene. an enzyme responsible generating reactive oxygen species (ROS) production osteoclast differentiation. Functional showed that upregulate ROS levels patient- derived osteoclasts, zebrafish models HEK293 cells. All data collected linked dysfunction proposed gene, offering potential therapeutic target modulating addressing PAM.</p><p II, shifted focus exploring its origins Ethiopian family with multiple affected members. Notably, mutations FLG Ethiopians, highlighting need investigate alternative contributors population. Whole-genome revealed co-segregating family, FLG2 - p.D13Y NOD2 p.A918S genes. Further genotyping case-control significant association variant. Additionally, previously p.A849V p.G908R also patients. These findings highlight importance etiology particularly populations.</p><p III, further explored role 2-amino ethanethiol dioxygenase (ADO) AD. idea arises from previous which GWAS variant was promoter ADO published Chromosome conformation capture (Capture Hi-C). expression significantly higher lesional compared non-lesional Zebrafish vitro demonstrated dysregulation impairs function enhances inflammation. This suggests plays critical maintaining homeostasis, contributing pathogenesis.</p><p IV, investigated gene's Swedish population, focusing on p.S2377X Genotypic analysis independent cohorts between reduced observed tissue carriers. underscores contribution risk, within population.</p><p dir="ltr">Collectively, thesis broadens understanding Novel insights provided identifying factor PAM, presenting first lead pinpointing condition. Furthermore, highlighted roles FLG2, NOD2, cause.</p><p dir="ltr">Genome serves tool identify cause diseases; Subsequent new into treatment approaches managing diseases.</p><h3>List scientific papers</h3><p dir="ltr">I. Rare coding link high mutilans<br><b>Sailan Wang</b>, Pernilla Nikamo, Leena Laasonen, Bjorn Gudbjornsson, Leif Ejstrup, Lars Iversen, Ulla Lindqvist, Jessica J Alm, Jesper Eisfeldt, Xiaowei Zheng, Sergiu-Bogdan Catrina, Fulya Taylan, Raquel Vaz, Mona Ståhle Isabel Tapia-Paez EMBO Molecular Medicine.2024;16(3):596-615. <a href="https://doi.org/10.1038/s44321-024-00035-z">https://doi.org/10.1038/s44321-024-00035-z</a><br><br>II. Uncommon associated population</p><p dir="ltr"><b>Sailan Julia K. Elmgren, Samina Asad, Marlene Ek, Kassahun Bilcha, Annisa Befekadu, Carl-Fredrik Wahlgren, Magnus Nordenskjöld, Tapia-Paez* Maria Bradley *. JID Innovations. 2024 Apr 29;4(4):100284. href="https://doi.org/10.1016/j.xjidi.2024.100284">https://doi.org/10.1016/j.xjidi.2024.100284</a><br><br>III. cysteamine dermatitis</p><p Josefin Lysell, Pelin Sahlén, Nordenskjold, Bradley* [Manuscript]<br><br>IV. patients</p><p Mahsa Tayefi, Axel Svedbom, Carl- Fredrik Emma Johansson, [Manuscript]</p><p dir="ltr">* Authors contributed equally</p>
Язык: Английский
Процитировано
0
Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)
Опубликована: Фев. 7, 2025
Abstract Background Diabetes mellitus (DM), characterized by hyperglycemia, is intricately linked with cardiovascular complications. Hyperglycemia induces oxidative stress, compromising mitochondria energy metabolism disturbances, leading to cardiomyocyte hypoxia and dysregulation of hypoxia-inducible factor-1α (HIF-1α), thereby exacerbating diabetic myocardial injury. Roxadustat (FG-4592), as an inhibitor HIF-PHD, reduces HIF-1α degradation regulates the transcription function downstream target genes. This study explores protective effect FG-4592 on myocardium further investigates specific mechanisms responsible for this action. Methods We established injury mice high glucose-induced rat models, administered pretreatment clarify effects related detecting changes in mitochondrial function, pathways. Results demonstrated cardioprotective regulating structure well maintaining stress balance myocardium. It stabilized HIF-1α, activated UCP2, enhanced PI3K/AKT/Nrf2 pathway, reducing superoxide production, improving respiratory potential, modulating markers cardiomyocytes. Conclusions exerts against stress. The mechanism upregulation which subsequently activate signaling pathway.
Язык: Английский
Процитировано
0
Cell Reports, Год журнала: 2025, Номер 44(3), С. 115403 - 115403
Опубликована: Март 1, 2025
Chronic inflammation and a decline in mitochondrial function are hallmarks of aging. Here, we show that the two mechanisms may be linked. We found interleukin-6 (IL6) suppresses settings where PGC1 (both PGC1α PGC1β) expression is low. This suppression mediated by JAK1/STAT1/3 axis, which activates HIF1α through non-canonical involving upregulation HIF1A ERRα transcription, subsequent stabilization protein ERRα. HIF1α, turn, inhibits ERRα, master regulator biogenesis, thus contributing to inhibition function. When expressed at higher levels, rescues boost baseline respiration, including under IL6-treated conditions. Our study suggests IL6 signaling axis could potential treatment for those inflammatory compromised.
Язык: Английский
Процитировано
0
Cell Calcium, Год журнала: 2025, Номер unknown, С. 103014 - 103014
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0