Most high-tech drugs and tissue engineering products based on human chondrocytes currently available on the market are aimed at restoring traumatic damage to cartilage tissue. However, in the presence of inflammation, their regenerative potential is significantly reduced, which limits their use in patients with osteoarthritis-one of the most common degenerative and inflammatory joint pathologies. The central element of the pathogenesis of osteoarthritis is inflammation-not classical acute inflammation, but rather chronic low-grade inflammation, primarily mediated by mechanisms of the innate immune response. Therefore, a key challenge is to enhance the anti-inflammatory effectiveness of cell-based drugs to broaden their indications to include degenerative diseases such as osteoarthritis and arthrosis. In recent years, cell-based drugs using stem cells, including mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), and stromal vascular fraction (SVF) cells, have been actively studied. Despite their confirmed safety in inflammatory processes, meta-analyses of clinical trials show limited effectiveness in improving symptoms and MRI data in the treatment of osteoarthritis. A promising direction appears to be the development of combined cell-based drugs that combine MSCs with M2-polarized macrophages; however, data on their clinical effectiveness are still insufficient. This review explores key cellular effectors of inflammation and its molecular mechanisms, potential strategies for creating tissue engineering products that possess not only regenerative but also pronounced anti-inflammatory effects. The development of such products will expand their application in the treatment of inflammatory-degenerative joint diseases.

Acute gouty arthritis (AGA) is a common inflammatory joint disease characterized by pain resulting from the deposition of monosodium urate (MSU) crystals into joints and surrounding tissues. RGFP966, a selective inhibitor of histone deacetylases 3 (HDAC3), can down-regulate the AIM2 inflammasomes. This study aimed to explore the mechanism of action of RGFP966 in MSU-induced AGA. MSU-induced AGA rats were treated with RGFP966 or colchicine, and physiological and pathological indicators were determined. The rat joint synovial tissues and kidneys pathological damage was observed by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA), Western blot, JC-1 staining, mitochondrial membrane potential (MMP) measurement, ATP assay, and immunofluorescence were applied to evaluate the effects of RGFP966 on the AIM2 inflammasomes and mitophagy. In MSU-induced AGA rats, RGFP966 significantly improved the gait score, the swelling degree and synovitis score. In addition, RGFP966 repressed the increased serum levels of IL-1β, IL-18, IL-6 and TNF-α, and reduced the protein levels of AIM2, Pro-caspase-1, Cleaved-caspase-1, ASC, Pro-IL-1β, and Cleaved-IL-1β in MSU-induced AGA rats. Furthermore, RGFP966 decreased the level of reactive oxygen species (ROS), increased the level of ATP and MMP, and promoted the levels of Pink1, Parkin and LC3-II. Collectively, RGFP966 significantly alleviated AGA, and the underlying mechanism is related to promote mitophagy by inhibiting the activation of the AIM2 inflammasomes.

This study aimed to develop a brucine (Bru) hydrogel-forming microneedle (Bru-HFM) delivery system that could achieve long-term, programmed drug release, through adjusting degree of cross-linking in polyvinyl alcohol (PVA)/carbomer 934P (CP) hydrogel. A one-way orthogonal experiment and a Franz diffusion cell were employed to optimize the preparation process. The resulting Bru-HFM exhibited favorable appearance, mechanical strength, and swelling properties. The drug release performance of the different drug-carrying sites of HFMs was compared. The results illustrated that in vivo drug release rate over 144 h was significantly higher in the needle body-carrying group (95.32%) than in the whole-microneedle (51.85%) and back-lining groups (57.39%). The amount of residue in the back-lining group was obvious, in line with expectations. The burst release rate of 78.81% could meet the high-dose demand during the acute phase of inflammation, whereas continuous release through the cross-linking network over 48-144 h achieved a total release rate of 95.32%. This covered the maintenance phase of chronic inflammation treatment, and the microneedles remained structurally intact at the end of drug release, permitting their detachable. The general pharmacodynamic evaluation results demonstrated that the pathological state of the ankle joints of rats with collagen-induced arthritis was significantly improved in the needle body-carrying group, which also exhibited significantly reduced serum levels of IL-6, IL-17, and TNF-α (all P < 0.05), indicating a significant therapeutic effect on rheumatoid arthritis. This study provides a new strategy and theoretical basis for designing HFMs for programmed drug release and inflammatory disease treatment.

The use of composite disease activity scores enables a pragmatic approach to the measurement of the level of disease activity in children with juvenile idiopathic arthritis (JIA). These tools are constructed through the combination of individual measures and provide a quantification of the absolute level of disease activity in one summary number on a continuous scale. The first composite score for JIA, named Juvenile Arthritis Disease Activity Score (JADAS), was published in 2009. It includes the following four variables: physician global assessment, parent/patient global assessment, active joints count, and an acute phase reactant. Its score is calculated as the arithmetic sum of the scores of its four items. Additional versions of the JADAS, which lack the acute phase reactant (clinical JADAS, cJADAS) or are specific to systemic JIA (systemic JADAS, sJADAS), were developed over the years. An important progress in the field has been represented by the definition of the cutoff values in the JADAS that distinguish the states of inactive disease or minimal, moderate, and high disease activity in JIA. These cutoffs may serve as therapeutic targets in the treat-to-target strategy. Recently, a JADAS version entirely composed of parent/patient-reported outcome measures has been developed and validated. This tool is well suited to implement remote patient monitoring, a form of telemedicine that may help to optimize disease control and reduce the pressure on healthcare systems. This review is aimed to describe the different versions of the JADAS and the main aspects of their developmental process.

Gout is among the most prevalent etiologies of chronic inflammatory arthritis in the United States, which is characterized by monosodium urate (MSU) monohydrate crystals deposition in the tissues.[1][2] Gout was first recognized even before the common era. Hence it is arguably the most understood and manageable disease among all rheumatic diseases.[3][4] 

Background/Objectives: Serum neurofilament light chain (sNfL) is an early and sensitive biomarker of polyneuropathy. This study compared the UmanDiagnostics enzyme-linked immunosorbent assay (ELISA), and Meso Scale Discovery (MSD) R-PLEX assay with the current gold-standard single-molecule array (Simoa) assay for sNfL measurement. Methods: sNfL levels were measured with Simoa, ELISA, and MSD R-PLEX in 330 serum samples from 73 individuals with a pathogenic transthyretin gene variant (TTRv) and in 165 healthy controls (HC) with ELISA and MSD R-PLEX. Results: Median sNfL levels, assessed in serum samples from TTRv individuals, differed across all assays (all p < 0.001). Passing-Bablok regression slopes were 1.01 (Simoa-ELISA), 1.00 (Simoa-MSD R-PLEX), and 1.02 (MSD R-PLEX-ELISA), with very strong correlations (all r > 0.8). Bland-Altman analysis showed mean differences of 0.1 ± 0.2 pg/mL (Simoa-ELISA), 0.7 ± 0.1 pg/mL (Simoa-MSD R-PLEX), and -0.6 ± 0.2 pg/mL (MSD R-PLEX-ELISA). In HC, sNfL levels positively correlated with age. Z-score normalization allowed for inter-assay comparison. Conclusions: The ELISA and MSD R-PLEX assays provide suitable alternatives for the Simoa assay to measure sNfL levels in carriers of a pathogenic TTR-gene variant. The differences in concentrations defined by the assays directly relate to the internal standard provided with the assays.