Ubiquitin-like modifier-activating enzyme 1 as a potential therapeutic target for aortic dissection DOI Creative Commons
Yao Wang,

Jinjin Zhang,

Yunsong Wang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 145, P. 113742 - 113742

Published: Dec. 5, 2024

Aortic dissection (AD) is a life-threatening aortopathy with no specific pharmacological therapy. Ubiquitination, highly orchestrated enzymatic cascade involving sequential E1-E2-E3 interactions, suggested to contribute the disease pathogenesis. However, role of E1 enzymes in AD progression remains unknown. In this study, we analyzed aortic transcriptional profiles human ascending dataset (GSE52093) and identified ubiquitin-like modifier-activating enzyme 1 (UBA1) as significantly up-regulated AD. This finding was further corroborated by immunohistochemistry RT-qPCR mouse model induced β-aminopropionitrile (BAPN). Treatment TAK-243, UBA1 inhibitor, prevented BAPN-induced formation mice attenuated medial degeneration, evidenced decreased elastin fragmentation (evaluated EVG scoring), reduced vascular smooth muscle cell loss (visualized α-SMA immunohistochemistry), less extracellular matrix degradation (indicated diminished MMP2 MMP9 expression RT-qPCR). Furthermore, TAK-243 treatment lesional macrophage accumulation activation, demonstrated CD68 analysis pro-inflammatory cytokine expression. vitro, activation observed macrophages (RAW264.7 cells) treated angiotensin II (AngII), AngII-induced at least partially through inhibition IκBα NF-κB p65 phosphorylation. conclusion, demonstrate that may facilitate promoting via signaling pathway. These findings reveal pathogenic for show potential UBA1-targeted therapy against disease.

Language: Английский

Latest Insights and Therapeutic Advances in Myelodysplastic Neoplasms DOI Open Access
Pasquale Niscola, Valentina Gianfelici, Marco Giovannini

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1563 - 1563

Published: April 19, 2024

Myelodysplastic syndromes/neoplasms (MDSs) encompass a range of hematopoietic malignancies, commonly affecting elderly individuals. Molecular alterations in the stem cell compartment drive disease pathogenesis. Recent advancements genomic profiling have provided valuable insights into biological underpinnings MDSs and expanded therapeutic options, particularly for specific molecularly defined subgroups. This review highlights diagnostic principles, classification updates, prognostic stratification systems, novel treatments, which could inform future clinical trials enhance management adult MDS patients,

Language: Английский

Citations

7
Critical cardiovascular complications during non-immunosuppressive therapy for VEXAS syndrome DOI Creative Commons
Yuna Saito, Satoshi Suzuki, Keigo Ikeda

et al.

Rheumatology Advances in Practice, Journal Year: 2025, Volume and Issue: 9(2)

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Challenging and Unique Diagnosis of VEXAS Syndrome: A Case Report DOI Creative Commons
Jowan Al‐Nusair, Olivia Lim,

Leena Alhusari

et al.

Journal of Investigative Medicine High Impact Case Reports, Journal Year: 2025, Volume and Issue: 13

Published: April 1, 2025

VEXAS syndrome, a myeloid-driven autoinflammatory disorder associated with somatic mutations in the UBA1 gene, was first described 2020 and presents significant diagnostic challenges due to its complex clinical features, including hematological abnormalities autoimmune manifestations. We describe case involving 64-year-old male presenting persistent anemia, weight loss, fatigue, fever, recurrent inflammatory symptoms. Diagnostic workup, imaging, serology, bone marrow biopsy, revealed characteristic findings, myeloid hyperplasia, vacuolization precursor cells. Genetic testing identified gene mutation, solidifying diagnosis of syndrome. The patient responded immunosuppressive treatment prednisone ruxolitinib, improvement This tells us importance considering syndrome patients refractory systemic inflammation abnormalities, particularly older males. Early recognition genetic are crucial for guiding decisions, as condition is progressive, often relapsing, requires multidisciplinary management.

Language: Английский

Citations

0
Rapid screening and monitoring of UBA1 mutations in VEXAS syndrome. DOI
Iván Martín, Elvira Mora, Rafael Hernani

et al.

Journal of Molecular Diagnostics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Visual analysis of the current status and trends of VEXAS syndrome research based on Citespace DOI

M. Mao,

Yifei Shao,

Shan Liu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Abstract Background: Understanding the current research status and hotspots of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Syndrome) syndrome provides reference guidance for diagnosis treatment syndrome. Method: Using Web Science Core Collection (WOSCC) literature retrieval platform, we filtered related to conducted a visual analysis publication volume, authors, publishing institutions, countries, keywords based on CiteSpace 6.3.R1. Conclusion: A total 382 articles were obtained through results filtering. The first article was published in 2020, 136 2024. According author collaboration network analysis, Beck David B from United States had highest number publications, with 27 articles. Institution country revealed that APHP National Institutes Health while count (n=121). top ten ranked by co-occurrence mainly revolve around definition, mechanism, clinical manifestations Keyword cluster indicates main features are inflammatory hematological manifestations, its mechanisms characteristics being relatively complex. In terms treatment, azacitidine interferon-gamma inhibitors, IL-1 receptor antagonists, tumor necrosis factor stem cell transplantation, biological agents mentioned succession. primary format is case reports. timeline shows sustained intensity onset disease present. Burstness focus 2020 definition classification From 2021 2022, shifted including immunological diseases such as myelodysplastic syndromes (MDS), chronic monocytic leukemia, systemic lupus erythematosus, polyarteritis nodosa. Conclusion: has gradually attracted attention researchers, an overall upward trend annual although publications low. Collaboration between authors institutions dispersed, primarily among their affiliated lacking cross-border cooperation. Currently, lies genetic mutations, immune regulation, multi-system pathologic presentations, which show high correlation MDS hematology. lack plans standardized protocols may be short duration absence large-scale trials. At present, analyses. summary, this still requires more practice, mechanisms, features, strategies should explored depth lay solid foundation effective prevention future.

Language: Английский

Citations

0
VEXAS Syndrome: A Comprehensive Review of Current Therapeutic Strategies and Emerging Treatments DOI Open Access
Safi Alqatari,

Abdulaziz A. Alqunais,

Shahad Mufeed Alali

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(22), P. 6970 - 6970

Published: Nov. 19, 2024

VEXAS syndrome is a recently identified autoinflammatory disorder resulting from somatic mutations in the UBA1 gene, leading to complex spectrum of severe inflammatory and hematologic manifestations. The absence established treatment guidelines variability clinical presentation make its management particularly challenging. Current therapeutic approaches are often based on limited evidence, their effectiveness remains inconsistent. This review seeks consolidate existing knowledge strategies for syndrome, offering critical evaluation efficacy addressing gaps current literature. As recognition grows, there an urgent need explore more targeted, effective treatments that can address both aspects disease. By providing comprehensive analysis landscape, this aims guide clinicians researchers toward developing effective, long-term life-threatening condition.

Language: Английский

Citations

2
Síndrome de VEXAS: a propósito de una serie de 2 casos DOI
Adrián Mayo-Juanatey,

María José Fernández-Llavador,

María del Mar Fernández-Garcés

et al.

Reumatología Clínica, Journal Year: 2024, Volume and Issue: 20(6), P. 341 - 344

Published: May 29, 2024

Citations

0
VEXAS syndrome: A 2-case series report DOI
Adrián Mayo-Juanatey,

María José Fernández-Llavador,

María del Mar Fernández-Garcés

et al.

Reumatología Clínica (English Edition), Journal Year: 2024, Volume and Issue: 20(6), P. 341 - 344

Published: June 1, 2024

Citations

0
Ubiquitin-like modifier-activating enzyme 1 as a potential therapeutic target for aortic dissection DOI Creative Commons
Yao Wang,

Jinjin Zhang,

Yunsong Wang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 145, P. 113742 - 113742

Published: Dec. 5, 2024

Aortic dissection (AD) is a life-threatening aortopathy with no specific pharmacological therapy. Ubiquitination, highly orchestrated enzymatic cascade involving sequential E1-E2-E3 interactions, suggested to contribute the disease pathogenesis. However, role of E1 enzymes in AD progression remains unknown. In this study, we analyzed aortic transcriptional profiles human ascending dataset (GSE52093) and identified ubiquitin-like modifier-activating enzyme 1 (UBA1) as significantly up-regulated AD. This finding was further corroborated by immunohistochemistry RT-qPCR mouse model induced β-aminopropionitrile (BAPN). Treatment TAK-243, UBA1 inhibitor, prevented BAPN-induced formation mice attenuated medial degeneration, evidenced decreased elastin fragmentation (evaluated EVG scoring), reduced vascular smooth muscle cell loss (visualized α-SMA immunohistochemistry), less extracellular matrix degradation (indicated diminished MMP2 MMP9 expression RT-qPCR). Furthermore, TAK-243 treatment lesional macrophage accumulation activation, demonstrated CD68 analysis pro-inflammatory cytokine expression. vitro, activation observed macrophages (RAW264.7 cells) treated angiotensin II (AngII), AngII-induced at least partially through inhibition IκBα NF-κB p65 phosphorylation. conclusion, demonstrate that may facilitate promoting via signaling pathway. These findings reveal pathogenic for show potential UBA1-targeted therapy against disease.

Language: Английский

Citations

0