Exploring the complexities of epigenetics in multiple sclerosis: A study involving meta-analysis of DNA methylation profiles, epigenetic drift, and rare epivariations DOI Creative Commons
Giulia Nicole Baldrighi, Rebecca Cavagnola, Davide Sacco

et al.

Multiple Sclerosis Journal - Experimental Translational and Clinical, Journal Year: 2024, Volume and Issue: 10(4)

Published: Oct. 1, 2024

Background Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory and neurodegenerative traits. Recently, DNA methylation has emerged as a promising field of investigation for elucidating dynamics characterizing MS development progression. Objectives This study aimed to comprehensively investigate the role epigenetics in analyzing profiles from blood brain tissues public datasets. Methods Employing meta-analytical framework differential analyses, extended beyond conventional analyses explore additional dimensions epigenetic regulation, including drift, age acceleration, rare epivariations. Results analysis were line with previously reported findings. No significant differences observed acceleration or global drift between cases controls. However, upon closer at gene level, distinctive patterns emerged, particularly within genes implicated neural biological functions. Conclusions These findings underscore modifications shaping pathology. Furthermore, unveiled exclusive presence epivariations cases, some which involved linked other diseases. highlights potential significance genetic aberrations driving susceptibility

Language: Английский

Rare genetic associations with human lifespan in UK Biobank are enriched for oncogenic genes DOI Creative Commons
Jun Young Park, Andrés Peña‐Tauber, Lia Talozzi

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 28, 2025

Abstract Human lifespan is shaped by genetic and environmental factors. To enable precision health, understanding how variants influence mortality essential. We conducted a survival analysis in European ancestry participants of the UK Biobank, using age-at-death (N=35,551) last-known-age (N=358,282). The associations identified were predominantly driven cancer. found lifespan-associated loci ( APOE , ZSCAN23 ) for common six genes where burden loss-of-function linked to reduced TET2 ATM BRCA2 CKMT1B BRCA1 ASXL1 ). Additionally, eight with pathogenic missense associated DNMT3A, SF3B1, TET2, PTEN, SOX21, TP53 SRSF2 RLIM Many these are involved oncogenic pathways clonal hematopoiesis. Our findings highlight importance factors driving most prevalent causes at population level, highlighting potential early testing identify germline somatic increasing one’s susceptibility cancer and/or death.

Language: Английский

Citations

1
The immunomodulatory of interleukin-33 in rheumatoid arthritis: A systematic review DOI
Renli Liu, Fangfang Wang, Xing Luo

et al.

Clinical Immunology, Journal Year: 2024, Volume and Issue: 265, P. 110264 - 110264

Published: May 31, 2024

Language: Английский

Citations

4
Exploring the shared gene signatures and mechanism among three autoimmune diseases by bulk RNA sequencing integrated with single-cell RNA sequencing analysis DOI Creative Commons
Xiao-Fang Liu, Bin Li, Yuxi Lin

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 7, 2025

Emerging evidence underscores the comorbidity mechanisms among autoimmune diseases (AIDs), with innovative technologies such as single-cell RNA sequencing (scRNA-seq) significantly advancing explorations in this field. This study aimed to investigate shared genes three AIDs-Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA) using bioinformatics databases, identify potential biomarkers for early diagnosis. We retrieved transcriptomic data of MS, SLE, RA patients from public databases. Weighted Gene Co-Expression Network Analysis (WGCNA) was employed construct gene co-expression networks disease-associated modules. Functional enrichment analyses Protein-Protein Interaction (PPI) network constructed. used machine learning algorithms select candidate evaluate their diagnostic value. The Cibersort algorithm scRNA-seq analysis performed key expression patterns assess infiltration immune cells MS patients. Finally, biomarkers' validated human mice experiments. Several were identified, which play crucial roles responses inflammation regulation. PPI highlighted hub genes, some selected through algorithms. Receiver Operating Characteristic (ROC) curve indicated that had high value (Area Under Curve, AUC >0.7). Immune cell pattern showed significant differences various revealed clusters upregulated single cerebrospinal fluid EAE mose model. Validation clinical samples confirmed biomarkers. identified proposed These are pivotal regulating responses, providing new targets theoretical basis diagnosis treatment diseases.

Language: Английский

Citations

0
Insights Into Disability and Disability Progression in People With Multiple Sclerosis Using Large‐Scale Healthcare Data DOI Creative Commons
Onur Dereli,

Jochen Behringer,

Achim Berthele

et al.

European Journal of Neurology, Journal Year: 2025, Volume and Issue: 32(4)

Published: March 30, 2025

ABSTRACT Background Identifying predictors for disability progression is crucial managing multiple sclerosis (MS). This study aims to explore levels of and informative factors in people with MS (PwMS) using healthcare data without detailed clinical information. Methods We conducted a case–control/cohort on from Bavaria's largest health insurance organization. The dataset included records assistive devices, nursing care, sick leaves, rehabilitation, drug therapies, diagnoses individuals MS, Crohn's disease (CD), rheumatoid arthritis (RA), controls (CTR) these diseases. used generalized linear models compare service utilization between other cohorts. A gradient‐boosting algorithm identified healthcare‐related associated PwMS, defined by increased care utilization. Results PwMS ( N = 11,961) demonstrated higher than CD 21,884), RA 105,450), CTR 82,677) groups, even at young ages. Besides expected risk like age, smoking, diabetes, psychiatric disorders, the prediction revealed that specific gynecological upper tract infections, asthma, thyroiditis were less likely need care. Conclusions Leveraging allows an objective assessment can identify progression. Our approach be applied studies large cohorts adapted diseases, measures, systems. Higher resources ages unmet improved treatment management strategies adults MS.

Language: Английский

Citations

0
Shared aetiology underlying multiple sclerosis and other immune mediated inflammatory diseases: Swedish familial co-aggregation and large-scale genetic correlation analyses DOI Creative Commons
Qianwen Liu,

Yuan Jiang,

Thomas Frisell

et al.

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 148, P. 103294 - 103294

Published: July 30, 2024

While multiple sclerosis (MS) affects less than 1 % of the general population, immune mediated inflammatory diseases (IMIDs) collectively influence 5-10 population. Understanding familial co-aggregation MS and other IMIDs carries important clinical public health implications that will enable early detection personalized treatment.

Language: Английский

Citations

3
Adverse childhood experiences and psychiatric comorbidity in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis in the Canadian longitudinal study on aging DOI Creative Commons
Julia O’Mahony, Çharles N. Bernstein, Ruth Ann Marrie

et al.

Journal of Psychosomatic Research, Journal Year: 2024, Volume and Issue: 187, P. 111893 - 111893

Published: Sept. 13, 2024

Language: Английский

Citations

1
Anti-inflammatory and antiresorptive effects of acyl substitution chromone derivatives in experimental model of rheumatoid arthritis DOI Creative Commons

D. I. Pozdnyakov,

K. N. Koryanova,

Karina K. Arustamyan

et al.

Pharmacy & Pharmacology, Journal Year: 2024, Volume and Issue: 11(5), P. 422 - 431

Published: Jan. 29, 2024

Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting mainly small and major joints. The development for new drugs the treatment of RAs constantly underway, while purposeful synthesis multi-targeted molecules can be considered promising direction anti-rheumatic drugs. aim. To evaluate anti-inflammatory antiresorptive effects acyl substituted chromone derivatives in experimental animal model rheumatoid arthritis. Materials methods. RА was modeled rats by injection suspension human type II collagen complete Freunds adjuvant (in ratio 1:1) under plantar aponeurosis hind limb animal. analyzed substances ciphers X3A7 X3A9 at dose 20 mg/kg reference drug dexamethasone 3 were administered intraperitoneally 28 days from moment RA modeling. On 7 th , 14 21 st experiment, severity clinical manifestations determined. After days, changes content cytokines blood serum assessed: tumor necrosis factor-α (TNF-α), interleukins (IL-1, IL-6, IL-10 IL-12). Changes myeloperoxidase activity concentrations matrix metalloproteinases (MMPs) 2 9 determined synovial tissues. Results. During study, it shown that use tested compounds X3A9, as well reference, contributed to decrease RA, starting day experiment. Subsequently, demonstrated animals treated with dexamethasone, cytokine decreased relation untreated animals: TNF-α – 57.8% ( p < 0.05), IL-1 64.1% IL-6 59.1% 0.05) IL-12 72.3% an increase level 75.4% 0.05). profile changed similarly when studied animals. It worth noting against background administration substances, 41.7 61.7 65.0% respectively, concentration MMP2 24.0 38.5 34.4% MMP9 13.5 37.9 35.6% Conclusion. study showed suppresses reactions resorptive processes tissues, which serve basis their further antirheumatic agents.

Language: Английский

Citations

0
Synovial transcriptome-wide association study implicates novel genes underlying rheumatoid arthritis risk DOI Creative Commons
Shouye Hu,

Hui-Miao Song,

Feng Jiang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 21, 2024

Abstract Background To identify rheumatoid arthritis (RA)-associated susceptibility genes and pathways through integrating genome-wide association study (GWAS) self-collected gene expression profile data. Methods A prediction model was built for synovium in 202 arthritic patients with matched genotype Using the FUSION software performed a transcriptome-wide (TWAS). GWAS summary data driven from largest RA meta-analysis (n = 276,020). Further analyses (conditional joint analysis, two types of causal differential analysis gene-set enrichment analysis) were used to deepen our understanding genetic architecture comorbidity aetiology RA. Results We identified eight conditionally independent associated after Bonferroni corrections, which three novel, such as TPRA1 ( P TWAS 9.59 × 10 − 6 ) HIP1 1.47 5 ). four that showed strong evidence, differentially expressed RA, explored possibility new uses known drugs. Conclusions By using relevant tissues synovium, led identification previously unknown RA-associated genes, shedding light on underlying

Language: Английский

Citations

0
Association of single nucleotide polymorphism rs3213119 variant of IL-12B gene in diagnosed Rheumatoid Arthritis patients DOI Creative Commons

I. Mirza,

Amir Rashid,

Amer Fakhr Amer Fakhr

et al.

Pakistan Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 40(5)

Published: April 3, 2024

To identify the

Language: Английский

Citations

0
Autoimmune Connective Tissue Disorders in Diabetic Patients DOI
Simona Caraiola, R. Ionescu

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 275 - 291

Published: Jan. 1, 2024

Citations

0