Interstitial lung diseases

The Lancet, Год журнала: 2022, Номер 400(10354), С. 769 - 786

Опубликована: Авг. 11, 2022

Язык: Английский

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Rheumatoid arthritis

The Lancet, Год журнала: 2023, Номер 402(10416), С. 2019 - 2033

Опубликована: Окт. 27, 2023

Язык: Английский

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EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis

Annals of the Rheumatic Diseases, Год журнала: 2021, Номер 81(1), С. 20 - 33

Опубликована: Авг. 18, 2021

To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) the management difficult-to-treat rheumatoid arthritis (D2T RA).

Язык: Английский

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Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance

Annual Review of Immunology, Год журнала: 2022, Номер 40(1), С. 295 - 321

Опубликована: Апрель 26, 2022

Macrophages are first responders for the immune system. In this role, they have both effector functions neutralizing pathogens and sentinel alerting other cells of diverse pathologic threats, thereby initiating coordinating a multipronged response. distributed throughout body—they circulate in blood, line mucosal membranes, reside within organs, survey connective tissue. Several reviews summarized their roles different physiological scenarios initiation or amplification pathologies. review, we propose that healthy macrophages rely on three hallmark properties: response specificity, context dependence, stimulus memory. When these properties diminished, macrophage's biological impaired, which turn results increased risk dysregulation, manifested by deficiency autoimmunity. We review evidence molecular mechanisms supporting functional hallmarks.

Язык: Английский

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Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis

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

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Nanoparticle-Mediated Multiple Modulation of Bone Microenvironment To Tackle Osteoarthritis

ACS Nano, Год журнала: 2024, Номер 18(15), С. 10625 - 10641

Опубликована: Апрель 2, 2024

Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN size 268 nm are stable under physiological conditions, be specifically taken up by macrophages through FN-mediated targeting, dissociated in oxidative microenvironment. dendrimer having intrinsic anti-inflammatory property FN both antioxidative properties display integrated functions ROS scavenging, hypoxia attenuation, macrophage M2 polarization, thus protecting from apoptosis creating designed bone immune microenvironment stem cell osteogenic differentiation. These characteristics lead to their effective treatment an OA model vivo reduce pathological changes joints including synovitis inhibition cartilage matrix degradation simultaneously promote differentiation repair. developed combining advantages bioactive treat may immunomodulatory therapy different diseases.

Язык: Английский

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Critical Role of Synovial Tissue–Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Сен. 3, 2021

Rheumatoid arthritis (RA) is a chronic prototypic immune-mediated inflammatory disease which characterized by persistent synovial inflammation, leading to progressive joint destruction. Whilst the introduction of targeted biological drugs has led step change in management RA, 30-40% patients do not respond adequately these treatments, regardless mechanism action drug used (ceiling therapeutic response). In addition, many who acheive clinical remission, quickly relapse following withdrawal treatment. These observations suggest existence additional pathways persistence that remain be identified and therapeutically. A major barrier for identification targets successful translation limited understanding cellular mechanisms operate within microenvironment sustain inflammation. Recent insights into heterogeneity tissue resident cells, including macropahges fibroblasts revealed distinct subsets cells differentially regulate specific aspects pathology, paving way interventions specifically modulate behaviour cells. this review, we will discuss phenotypic functional how diversity contributes We critical interactions between cell types state establishing checkpoints synovium designed suppress inflammation restore homeostasis. propose failure leads emergence imprinted pathogenic fibroblast states drive Finally, strategies could employed target RA.

Язык: Английский

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Focus on Sex and Gender: What We Need to Know in the Management of Rheumatoid Arthritis

Journal of Personalized Medicine, Год журнала: 2022, Номер 12(3), С. 499 - 499

Опубликована: Март 20, 2022

Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting mostly women with female/male ratio of 3:1. It characterized by symmetrical polyarthritis, leading to progressive joint damage. Sex differences have been reported in terms disease course and characteristics, influencing patients outcome measures (PROMs) pain perception, ultimately male-female disparities treatment response. Notwithstanding, sex gender discrepancies are still under-reported clinical trials. Therefore, there consistent need for precise reference issues RA studies improve treat-to-target achievement. This narrative review explores the above-mentioned aspects discussing latest core principles recommendations, from safety early concept management, difficult-to-treat notions, up most recent debate on vaccination. Our final purpose evaluate how can impact current management guidelines this issue be integrated effective control.

Язык: Английский

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Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study

Frontiers in Public Health, Год журнала: 2022, Номер 10

Опубликована: Июнь 30, 2022

Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether are causally associated with RA. Seven sleep-related traits were chosen from published Genome-Wide Association Study (GWAS): short duration, frequent insomnia, any getting up, morningness (early-to-bed/up habit), snoring, 27, 53, 57, 70, 274, 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) obtained as instrumental variables (IVs) for these traits. Outcome a public GWAS study that included 14,361 cases 43,923 European Ancestry controls. The relationship disturbances RA risk evaluated by (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, median, weight mode methods. Regression pleiotropy residual sum outlier (MR-PRESSO) used test horizontal pleomorphism outliers. There was no evidence of link insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), OR: 1.09; CI: 0.85-1.42; 0.489), duration 0.65, 0.38-1.10, 0.269), up 0.56, 0.13-2.46, 0.442), 2.59; 0.73-9.16; 0.142), or snoring 0.95; 0.68-1.33; 0.757). Short (6h) had effect on RA, supported IVW median (OR: 1.47, 1.12-1.94, 0.006; 1.43, 95%CI:1.01-2.05, 0.047). Sensitivity showed results stable. Our findings imply is linked an increased Therefore, length should be considered in disease models, physicians advise people avoid practices lower

Язык: Английский

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'Difficult to treat' rheumatoid arthritis: current position and considerations for next steps

RMD Open, Год журнала: 2022, Номер 8(2), С. e002387 - e002387

Опубликована: Июль 1, 2022

The European Alliance of Associations for Rheumatology recently defined difficult to treat (D2T) rheumatoid arthritis (RA) and provided points consider in its management. This review summarises the key concepts D2T-RA that underpinned this recent guidance. is primarily characterised by failure at least two different mechanism action biologic/targeted synthetic disease-modifying antirheumatic drug (DMARDs) with evidence active/progressive disease. basis progressive disease, however, not limited clear inflammatory joint pathology, capturing wider contributors treatment cycling such as comorbidity, obesity fibromyalgia. means comprises a heterogeneous population, proportion within exhibiting bona fide treatment-refractory management consider, emphasise importance checking presence pathology before further change. suggests additional considerations definition D2T-RA, potential value identifying D2T traits intervening development state need real world targeted DMARD population compare trial data. Finally, asks whether implies effectively from outset, pharmacological non-pharmacological approaches address effectively.

Язык: Английский

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