Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(8), С. 3561 - 3575
Опубликована: Апрель 8, 2024
Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment.
Язык: Английский
Clinical and Experimental Rheumatology, Год журнала: 2021, Номер 39(3), С. 445 - 452
Опубликована: Май 21, 2021
Язык: Английский
Процитировано
288
The Lancet, Год журнала: 2023, Номер 402(10416), С. 2019 - 2033
Опубликована: Окт. 27, 2023
Язык: Английский
Процитировано
283
Psoriasis Targets and Therapy, Год журнала: 2016, Номер unknown, С. 7 - 7
Опубликована: Фев. 1, 2016
Abstract: Psoriasis is a prevalent, chronic inflammatory disease of the skin, mediated by crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as antigen presenting cells (APCs) T cells. Exclusive cellular "responsibility" for induction maintenance psoriatic plaques has not been clearly defined. Increased proliferation keratinocytes endothelial in conjunction with APC/T cell/monocyte/macrophage inflammation leads to distinct hyperplasia that characteristic lesional skin. Despite identification numerous susceptibility loci, no single genetic determinant identified responsible psoriasis. Thus, other triggers disease, environmental, microbial complex interactions must also be considered participants development this multifactorial disease. Recent advances therapeutics, especially systemic so-called "biologics" have provided new hope identifying critical targets drive psoriasis pathogenesis. recognition co-morbidities autoimmune disorders associated psoriasis, including bowel multiple sclerosis, rheumatoid arthritis, lupus erythematosus suggest common signaling elements mediators may direct In review, we discuss pathways mediate share these pathways. Keywords: autoimmunity, immunosuppression
Язык: Английский
Процитировано
243
BMJ, Год журнала: 2024, Номер unknown, С. e070856 - e070856
Опубликована: Янв. 17, 2024
Abstract Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid present pain, swelling, and stiffness that typically affects symmetrically distributed small large joints. Without effective treatment, significant joint damage, disability, work loss develop, owing to chronic inflammation lining (synovium). Over past 25 years, management this condition has been revolutionized, resulting in substantially higher levels disease remission better long term outcomes. This improvement reflects a paradigm shift towards early aggressive pharmacological intervention coupled proliferation treatment choice, turn related enhanced pathobiological understanding advent new drugs for arthritis. Following an overview these developments from historical perspective, general audience mind, review focuses on newer, targeted treatments ever evolving landscape. The highlights ongoing areas debate unmet need, including proportion patients persistent, difficult-to-treat disease, despite recent advances. Also discussed are personalized, strategic approaches individual patients, role imaging clinical decision making, goal sustained, drug free prevention future.
Язык: Английский
Процитировано
95
Science Translational Medicine, Год журнала: 2024, Номер 16(742)
Опубликована: Апрель 10, 2024
It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal scores patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) identify an 815-gene associated biopsy samples from established RA who had limited at arthroplasty. then validated this finding independent cohort of early untreated little Single-cell RNA sequencing analyses indicated most these 815 genes were robustly expressed by lining layer fibroblasts. Receptor-ligand interaction analysis predicted cross-talk between human fibroblasts and dorsal root ganglion neurons expressing calcitonin gene–related peptide (CGRP + ). Both fibroblast culture supernatant netrin-4, which abundantly was within GbGMI-identified pain-associated module, increased branching pain-sensitive murine CGRP vitro. Imaging solvent-cleared tissue humans revealed pain-sensing encasing blood vessels growing into hypertrophic papilla. Together, findings support model whereby express enhance growth regions hypertrophy RA.
Язык: Английский
Процитировано
24
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Апрель 15, 2024
Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory in cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and bowel disease. We review IL-23 biology, signaling IMIDs, the effect inhibition treating these diseases. propose studies to advance biology unravel differences response anti–IL-23 therapy. Experimental evidence generated from investigations could establish novel molecular ontology centered around IL-23–driven diseases, improve upon current approaches IMIDs with inhibition, ultimately facilitate optimal identification patients and, thereby, outcomes.
Язык: Английский
Процитировано
23
The FASEB Journal, Год журнала: 2025, Номер 39(1)
Опубликована: Янв. 6, 2025
The activation of acid-sensing ion channel 1a (ASIC1a) in response to extracellular acidification leads an increase calcium influx, thereby exacerbating the degeneration articular chondrocytes rheumatoid arthritis (RA). It has been suggested that inhibition influx could potentially impede chondrocyte ferroptosis. cystine transporter, solute carrier family 7 member 11 (SLC7A11), is recognized as a key regulator Recent studies suggest tumor suppressor gene p53 facilitates induction ferroptosis by suppressing upregulation SLC7A11. This process mediated nuclear factor erythroid 2-related 2 (NRF2), transcription integral maintenance cellular redox homeostasis and regulation inflammatory responses. study aims investigate role ASIC1a RA determine involvement p53/NRF2/SLC7A11 pathway its underlying mechanism. In vitro experiments revealed acidosis induces reduces expression NRF2 SLC7A11 chondrocytes. Moreover, significantly increased protein levels Pifithrin-α (PFN-α), inhibitor, mitigated acidosis-induced restored diminished Furthermore, PcTx-1, inhibited acidification-induced ferroptosis, enhanced NRF2, reduced expression. vivo demonstrated ASIC1a-specific inhibitor PcTx-1 ameliorated histopathological characteristics ankle joints collagen-induced (CIA) mice, decreased expression, These findings may mitigate RA, via pathway.
Язык: Английский
Процитировано
3
Drug Design Development and Therapy, Год журнала: 2013, Номер unknown, С. 87 - 87
Опубликована: Дек. 1, 2013
Abstract: Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule expressed on surface of B cells. It was first used in treatment non-Hodgkin's lymphoma and later approved for rheumatoid arthritis (RA) does not respond adequately to disease-modifying antirheumatic drugs, including anti-tumor-necrosis-factor (TNF) biologics. Sustained efficacy RA can be achieved by repeated courses rituximab. However, optimal dose retreatment schedule rituximab remains established. Seropositivity, complete cell depletion shortly after treatment, previous failure no more than one anti-TNF agent are three factors associated with greater clinical benefits Infusion reaction occurs approximately 25% patients, incidence reduces subsequent exposure. Immunogenicity compound 11% but this correlate its depletion. Extended observation randomized controlled trials reveal significant increase serious infections related compared placebo groups, infection rate static over time. Repeated hypogammaglobulinemia, which may risk serious, rarely opportunistic, infections. Reactivation occult hepatitis has been reported patients receiving rituximab, tuberculosis observed. Screening baseline serum immunoglobulin G level status (including infection) important, especially Asian countries where prevalent. The rare fatal progressive multifocal leukoencephalopathy linked use noted. Postmarketing surveillance registry data, particularly Asia, necessary establish long-term safety RA. Keywords: biologics, B-cell depletion, arthritis, prognosis
Язык: Английский
Процитировано
154
Drug Design Development and Therapy, Год журнала: 2018, Номер Volume 13, С. 57 - 70
Опубликована: Дек. 1, 2018
Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and systemic manifestations, such as anemia, fatigue, osteoporosis, increased risk for cardiovascular diseases. The pathogenesis of RA driven complex network proinflammatory cytokines, with pivotal role IL-6 tumor necrosis factor (TNF). management has been dramatically changed during the last years introduction treat-to-target approach aiming to achieve an acceptable control. Nowadays, TNF inhibitors (TNFis) are most frequently prescribed class biologic therapies, but significant proportion patients experiencing failure TNFi led development alternative therapeutic options targeted on different pathways. Considering increasing number RA, there growing interest in identification potential predictors clinical response each available mechanism action, aim drive toward personalized according concept precision medicine. Tocilizumab (TCZ) first humanized anti-IL-6 receptor subunit alpha (anti-IL-6R) monoclonal antibody approved treatment refractory methotrexate or TNFis. TCZ inhibits both cis- trans-signaling cascades involving Janus kinase-signal transducer activator transcription pathway, playing crucial modulating not only joint inflammation also previously mentioned extra-articular manifestations comorbidities bone loss, depression, type 2 diabetes, risk. In this review, moving from pathogenetic insights evidence-based data randomized controlled trials real-life observational studies, we will discuss drivers selection patient candidates receive TCZ, order clarify current positioning drug algorithm RA. Keywords: IL-6, profiling, trials, efficacy,
Язык: Английский
Процитировано
131
Current Pharmaceutical Design, Год журнала: 2013, Номер 19(35), С. 6375 - 6381
Опубликована: Сен. 1, 2013
Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the progressive destruction of joint causes morbidity. It also associated with an increased risk atherosclerosis, can result cardiovascular and mortality. The therapeutic goal to control systemic inflammation obtain not only remission symptoms, but improve general state health. Although recent biologic immunosuppressive therapies targeting pro-inflammatory cytokines have spawned paradigm shift regarding prognosis RA, these possess inherent side effects. Also, early diagnosis remains confounded by uncertainty. While mechanisms responsible for onset RA remain unclear, reactive oxygen species (ROS) play significant role pathogenesis RA. ROS central both upstream downstream NF-κB TNFα pathways, are located at center response. Among ROS, hydroxyl radical most harmful, molecular hydrogen (H2) selective scavenger this species. Recently, it has been shown that H2 useful when administered along conventional therapy as acts reduce oxidative stress patients. Especially stage, showed potential, seemed assist treatment decisions possible expectations potential benefits reducing stress, resulting from factors, raised discussed here. They include prevention related well validity
Язык: Английский
Процитировано
125