Heart Rhythm, Journal Year: 2025, Volume and Issue: unknown
Published: May 1, 2025
Language: Английский
Journal of Molecular and Cellular Cardiology, Journal Year: 2024, Volume and Issue: 187, P. 80 - 89
Published: Jan. 1, 2024
Language: Английский
Citations
5
Intractable & Rare Diseases Research, Journal Year: 2023, Volume and Issue: 12(3), P. 170 - 179
Published: Aug. 17, 2023
VEXAS syndrome, is a hemato-inflammatory chronic disease characterized with predominantly rheumatic and hematologic systemic involvement. It was first described in 2020 by group of researchers the United States. syndrome rare condition that primarily affects adult males caused mutation UBA1 gene located on X chromosome. Its pathogenesis related to somatic affecting methionine-41 (p.Met41) UBA1, major E1 enzyme initiates ubiquitylation. Mutant lead decreased ubiquitination activated innate immune pathways inflammation occur. The specific mechanism which leads clinical features not yet fully understood. newly define adult-onset inflammatory manifested treatment-refractory fevers, arthritis, chondritis, vasculitis, cytopenias, typical vacuoles hematopetic precursor cells, neutrophilic cutaneous pulmonary inflammation. Diagnosing can be challenging due its rarity overlap symptoms other conditions. Genetic testing identify essential for definitive diagnosis. Currently, there no known cure treatment mainly focuses managing symptoms. This may involve use anti-inflammatory medications, immunosuppressive drugs, supportive therapies tailored individual patient's needs. Due recent discovery ongoing research being conducted better understand pathogenesis, features, potential options. In this review article, clinical, diagnostic approaches were evaluated light latest literature data.
Language: Английский
Citations
12
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2261 - 2261
Published: Feb. 13, 2024
Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level cartilaginous structures and tissues rich in proteoglycans. The pathogenesis disease complex still incompletely elucidated. data support important role particular genetic predisposition, with HLA-DR4 being considered an allele that confers major risk occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers development clinical manifestations, causing degradation proteins release cryptic cartilage antigens. Both humoral cellular immunity play essential roles occurrence perpetuation autoimmunity inflammation. Autoantibodies anti-type II, IX XI collagens, anti-matrilin-1 anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted increased titers, correlated activity prognostic factors. Innate cells, neutrophils, monocytes, macrophages, natural killer lymphocytes eosinophils found perichondrium cartilage, together activated antigen-presenting C3 deposits immunoglobulins. Also, T cells decisive disease, relapsing TH1-mediated condition. Thus, secretions interferon γ, interleukin (IL)-12 IL-2 highlighted. “inflammatory storm” formed network pro-inflammatory cytokines chemokines actively modulates recruitment infiltration various source Along RP, VEXAS syndrome, another systemic determinism, has etiopathogenesis known, it involves activation innate immune system through different pathways appearance cytokine storm. manifestations syndrome include phenotype often similar to which raises diagnostic problems. management RP includes common immunosuppressive therapies whose main goal control manifestations. objective this paper detail etiopathogenetic mechanisms rare summarizing latest presenting distinct features these mechanisms.
Language: Английский
Citations
4
Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 961 - 961
Published: Feb. 27, 2024
Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied field cancerization in BLCA using multi-sample- multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations loss chromosome Y (LOY). analysed 277 samples histologically normal urothelium, 145 tumors 63 blood from 52 males 15 females, in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification early aberrations urothelium patients. Overall, 45% patients exhibited at least one alteration sample. Recurrence analysis resulted 16 hotspots composed either gains copy number neutral heterozygosity (CN-LOH) or deletions CN-LOH, encompassing well-known new driver genes. Conservative assessment LOY showed 29%, 27% 18% LOY-cells tumors, respectively. provide proof principle that our can characterize earliest preconditioning to development. Frequent urothelium-derived tissues suggest its involvement BLCA.
Language: Английский
Citations
4
Blood Advances, Journal Year: 2024, Volume and Issue: 8(13), P. 3453 - 3463
Published: April 12, 2024
Clonal hematopoiesis (CH) is an age-associated phenomenon leading to increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery CH clinically common yet evidence-based guidelines effective management strategies prevent adverse health outcomes are lacking. To address this gap, prospective CHIVE (clonal inflammation in vasculature) registry biorepository was created identify monitor individuals at risk, support multidisciplinary clinics, refine taxonomy standards practice for mitigation. Data from first 181 patients enrolled recapitulate molecular epidemiology biobank-scale retrospective studies, with DNMT3A, TET2, ASXL1, TP53 as most commonly mutated genes. Blood counts across all hematopoietic lineages trended lower CH. In addition, had higher rates end dysfunction, particular chronic kidney disease. Among CH, variant allele frequency independently associated presence cytopenias progression malignancy, whereas other high-risk clone features were not clear. Notably, accumulation multiple distinct also progression, supporting a recently published score. Surprisingly, ∼30% clinics adjudicated having clonal indeterminate potential, highlighting need purpose-built assays field. Maintenance well-annotated cohort continued expansion institutions underway will be critical understanding how thoughtfully care patient population.
Language: Английский
Citations
4
Bone Marrow Transplantation, Journal Year: 2024, Volume and Issue: 59(10), P. 1349 - 1359
Published: July 14, 2024
Abstract Hematopoietic stem cell transplantation (HCT) represents a curative treatment option for certain malignant and nonmalignant hematological diseases. Conditioning regimens before HCT, the development of graft-versus-host disease (GVHD) in allogeneic setting, delayed immune reconstitution contribute to early late complications by inducing tissue damage or humoral alterations. Hemostasis and/or complement system are biological regulatory defense systems involving cellular reactions variably involved these after HCT. The hemostasis have multiple interactions, which been described both under physiological pathological conditions. They share common targets, such as endothelium, suggests interactions pathogenesis several serious phase Complications interfere with each other thus include transplant-associated thrombotic microangiopathy (HSCT-TMA), sinusoidal obstruction syndrome/veno-occlusive (SOS/VOD), GVHD. Here, we review current knowledge on changes HCT how may define clinical impact.
Language: Английский
Citations
4
Aging and Cancer, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 28, 2025
ABSTRACT Background Cancer's inherent ability to evolve presents significant challenges for its categorization and treatment. Cancer evolution is driven by genetic, epigenetic, phenotypic diversity influenced microenvironment changes. Aging plays a crucial role altering the inducing substantial genetic epigenetic heterogeneity within an individual's somatic cells even before cancer initiation. Objectives This review highlights clinical significance of mechanisms in evolution, focusing on hematopoietic solid tumors. The aims explore opportunities integrating evolutionary principles data science into research. Methods synthesizes recent advancements omics technologies, single‐cell sequencing, barcoding elucidate aging's evolution. Results Epigenetic mechanisms' high plasticity generates heritable diversity, driving malignant toward poor prognosis. Advances sequencing enable precise detection tracking biomarkers, allowing early, personalized interventions. Incorporating research has potential map, predict, prevent effectively. Conclusion Understanding through novel technologies analysis offers proactive approach prevention By predicting key events leveraging strategies, patient outcomes can be improved, healthcare burdens reduced, marking transformative shift oncology.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 7, 2025
Abstract Multicellular organisms are confronted not only with mutation in germline, but also mutations emerging somatic cells. Somatic can lead cancers and possibly contribute to aging phenotypes. Prevailing wisdom suggests limited by evolved defences, either targeting DNA or post-mutational cellular states. Here, I analyse simple models for metazoans humans particular, incorporating the possibility that rate trades-off of organism longevity, defined as age at which natural selection becomes negligible. The assume acts reduce prevent disease, both selecting longer lifespan. We detail equilibrium conditions find coevolutionary oscillations under certain parameter combinations. Notably, disease prevention mutational tolerance this explaining empirical cross-species patterns longevity vs. rate. conclude cancer particular have required characteristics be mediators – lifespan coevolution. results from coevolution incidences other diseases conditions, including aging.
Language: Английский
Citations
0
Hypertension, Journal Year: 2025, Volume and Issue: 82(3)
Published: Feb. 19, 2025
Language: Английский
Citations
0
Annals of the Rheumatic Diseases, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Mosaic chromosomal alterations (mCAs) increase with age and are associated age-related diseases. The association between mCAs rheumatoid arthritis (RA), particularly late-onset RA (LORA), has not been explored. were detected in peripheral blood samples from 2 independent Japanese datasets (Set 1: 2107 cases 86,998 controls; Set 2: 2359 controls). associations evaluated each dataset using logistic regression models meta-analysis. In dataset, the effect sizes of mosaic loss Y (mLOY) polygenic risk score (PRS) males was evaluated, a meta-analysis subsequently performed. interaction mLOY PRS assessed. These applied separately to RA, LORA, young-onset (YORA). increased significantly LORA (odds ratio [OR] = 1.43, P .0070). We observed negative YORA (OR 0.66, .0034). On other hand, we found consistently autosomal or X YORA. lower for than high cell fraction strengthened (P .0036), whereas mLOY. characterised by presence burden but YORA, supports different gene-environment interactions subsets. data suggest that distinct pathophysiological mechanisms underlie development
Language: Английский
Citations
0