Signs Of Arthritis Research Articles

Giant Cell Tumor of Capitate with Secondary Aneurysmal Bone Cyst: A Case Report

Abstract Background Giant cell tumors (GCTs) of the carpal bones are rare. GCTs of the hand tend to be aggressive, could result in multifocal presentation, and have a high rate of recurrence. Case Description We report a rare case of GCT of the capitate with secondary aneurysmal bone cyst (ABC) in a 40-year-old man. The patient presented with complaints of pain and swelling over his right wrist since 6 months. Radiographs showed the presence of a lytic lesion in the capitate. Magnetic resonance imaging scanning revealed a well-defined, lobulated, multiseptate lytic lesion involving the entire capitate, extending into its subarticular regions. Fine-needle aspiration revealed findings suggestive of a GCT. He underwent en-bloc excision of the capitate, bone grafting of the defect using an appropriately sized bicortical iliac crest autograft, and third carpometacarpal and midcarpal fusion. Histopathological examination of the lesion confirmed the presence of a GCT, with a secondary ABC. At 3 years following surgery, he was asymptomatic with no signs of tumor recurrence, radiocarpal arthritis, or instability. He was able to perform 45 and 60 degrees of wrist extension and flexion, respectively. Literature Review To our knowledge, there are no prior reported cases of GCT of the capitate with a secondary ABC. Clinical Relevance GCTs of the hand in general have a high rate of recurrence. The presence of a super-added ABC could further increase this risk. In the authors' opinion, en-bloc excision of the affected bone, reconstruction of the defect, and appropriate fusion is the optimal mode of management of these cases.

Intestinal epithelial expression of human TNF is sufficient to induce small bowel inflammation and sacroiliitis mimicking human Spondyloarthritis.

Gut and joint disease commonly co-occur in spondyloarthritis (SpA). Up to 50% of SpA-patients show signs of subclinical gut inflammation and 10% evolves into inflammatory bowel disease (IBD). However, the mechanisms underlying this gut-joint axis are still unclear. Here we tested the hypothesis whether restricted expression of a pro-inflammatory cytokine in the intestine may trigger onset of combined gut and joint inflammation. Intestinal expression of human TNF (hTNF) was achieved by driving hTNF gene expression under control of the rat FAPB2 promoter, creating a new animal model, the TNFgut mice, which expresses hTNF in the proximal intestinal tract. Intestinal-specific TNFgut mice were examined for pathological changes in the intestine and extra-intestinal tissues by means of histology, qPCR and flow cytometry, along with 16S sequencing on stools. Local expression of hTNF in the epithelium of the small intestine induces a pro-inflammatory state of the proximal intestinal tract with epithelial alterations and induction of members of the S100 family, as well as local upregulation of T helper 17 and regulatory T cells, but no obvious signs of dysbiosis. Curiously, TNFgut mice develop sacroiliitis (p< 0.05) in addition to small bowel inflammation (p< 0.05). However, no signs of peripheral arthritis nor enthesitis could be documented. Intestinal expression of hTNF is sufficient to initiate a pro-inflammatory cascade culminating in small bowel inflammation and sacroiliitis. Thus, gut-derived cytokines are sufficient to induce spondyloarthritis.

Therapeutic Potential of Olax subscorpioidea Root Extracts in Managing Inflammatory Conditions: A Preclinical Study

Olax subscorpioidea, a plant species endemic to tropical Africa, has long been utilized in traditional medicine for its purported anti-inflammatory and analgesic properties. This preclinical study evaluates the therapeutic potential of Olax subscorpioidea root extracts in managing inflammatory conditions, specifically in a Freund’s adjuvant (CFA)-collagen type II induced arthritis model in albino rats. Both aqueous and ethanol extracts were prepared and assessed for their effects on inflammatory parameters, including cytokine levels, paw edema, joint swelling, and histopathological changes. The study found that both extracts significantly reduced inflammation and clinical signs of arthritis, with the ethanol extract demonstrating a broader range of bioactive compounds and potentially greater efficacy. Mechanistic insights suggest that the extracts exert their effects through inhibition of pro-inflammatory enzymes, modulation of cytokine production, and enhancement of antioxidant activity. Safety and toxicity assessments confirmed the non-toxic nature of the extracts at tested doses. These findings validate the traditional use of Olax subscorpioidea for inflammatory conditions and support its potential integration into modern therapeutic regimens. Future research should focus on dosage optimization, long-term effects, and clinical trials to further establish the efficacy and safety of Olax subscorpioidea root extracts in human subjects. Keywords: Olax subscorpioidea, Root Extracts, Inflammatory Conditions, Preclinical Study.

Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a potentially devastating autoimmune disease. The great majority of patients with RA are seropositive for anti-citrullinated protein antibodies (ACPAs), rheumatoid factors, or other autoantibodies. The onset of clinically apparent inflammatory arthritis meeting classification criteria (clinical RA) is preceded by ACPA seropositivity for an average of 3-5 years, a period that is designated as 'at-risk' of RA for ACPA-positive individuals who do not display signs of arthritis, or 'pre-RA' for individuals who are known to have progressed to developing clinical RA. Prior studies of individuals at-risk of RA have associated pulmonary mucosal inflammation with local production of ACPAs and rheumatoid factors, leading to development of the 'mucosal origins hypothesis'. Recent work now suggests the presence of multiple distinct mucosal site-specific mechanisms that drive RA evolution. Indicatively, subsets of individuals at-risk of RA and patients with RA harbour a faecal bacterial strain that has exhibited arthritogenic activity in animal models and that favours T helper 17 (TH17) cell responses in patients. Periodontal inflammation and oral microbiota have also been suggested to promote the development of arthritis through breaches in the mucosal barrier. Herein, we argue that mucosal sites and their associated microbial strains can contribute to RA evolution via distinct pathogenic mechanisms, which can be considered causal mucosal endotypes. Future therapies instituted for prevention in the at-risk period, or, perhaps, during clinical RA as therapeutics for active arthritis, will possibly have to address these individual mechanisms as part of precision medicine approaches.

A novel inhibitor of class IIa histone deacetylases attenuates collagen-induced arthritis.

Most inhibitors of histone deacetylases (HDACs) are not selective and are cytotoxic. Some have anti-inflammatory activity in disease models, but cytotoxicity prevents long-term uses in non-fatal diseases. Inhibitors selective for class IIa HDACs are much less cytotoxic and may have applications in management of chronic inflammatory diseases. LL87 is a novel HDAC inhibitor examined here for HDAC enzyme selectivity. It was also investigated in macrophages for cytotoxicity and for inhibition of lipopolysaccharide (LPS)-stimulated cytokine secretion. In a rat model of collagen-induced arthritis, LL87 was investigated for effects on joint inflammation in Dark Agouti rats. Histological, immunohistochemical, micro-computed tomography and molecular analyses characterise developing arthritis and anti-inflammatory efficacy. LL87 was significantly more inhibitory against class IIa than class I or IIb HDAC enzymes. In macrophages, LL87 was not cytotoxic and reduced both LPS-induced secretion of pro-inflammatory cytokines, and IL6-induced class IIa HDAC activity. In rats, LL87 attenuated paw swelling and clinical signs of arthritis, reducing collagen loss and histological damage in ankle joints. LL87 decreased immune cell infiltration, especially pro-inflammatory macrophages and osteoclasts, into synovial joints and significantly reduced expression of pro-inflammatory cytokines and tissue-degrading proteases. A novel inhibitor of class IIa HDACs has been shown to have an anti-inflammatory and anti-arthritic profile distinct from current therapies. It is efficacious in reducing macrophage infiltration and joint inflammation in a chronic model of rat arthritis.

Perilunate Fracture-Dislocation: Results at Mean Follow-Up of 7 Years after ORIF.

Background: Perilunate fracture-dislocations are frequently associated with a high risk of developing post-traumatic arthritis. Current studies indicate that during mid-term follow-ups, radiological signs of arthritis do not appear to correspond with functional score. The aim of this study was to assess the occurrence of posttraumatic arthritis and the wrist function after perilunate dislocations (PLD) and fracture dislocations at a mid-term follow-up of 7 years. Methods: We report the clinical and radiological outcomes of 17 wrists treated for PLD or fracture-dislocation by open reduction and internal fixation through a dorsal approach with dorsal ligament repair. Functional outcomes were evaluated using the short version of the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), the Patient-Rated Wrist Evaluation questionnaire (PRWE) and the Mayo Wrist Score (MWS). Results of radiographs were assessed using the Herzberg Radiological Scoring Chart. Results: The MWS showed five excellent, five good, five fair and two poor results with an average score of 81%. Radiological analysis using the Herzberg classification revealed midcarpal and/or radiocarpal arthritis in 65% of cases, lunate collapse in 59% and an increase in the mean ulnar translocation ratio in 53% of the cases. Complications included one case of lunate osteonecrosis and one case of stage 3 scapholunate advanced collapse that required revision surgery. Conclusions: Although the clinical and functional outcomes are favourable at mid-term follow-up, radiological evaluation shows a progression towards osteoarthritis (OA). Further research is warranted to refine treatment strategies and investigate factors influencing the development of OA. Level of Evidence: Level IV (Therapeutic).

The diabetic sausage toe: Prevalence, presentation and outcomes.

Osteomyelitis (OM) in diabetic foot infection could have many presentations such as an infected ulcer spreading to the bone or superimposed to Charcot neuroarthropathy. However, the sausage toe as a diabetic OM presentation was very rarely investigated; therefore, this study aims to assess the prevalence and signs of this presentation along with treatment modalities and outcomes. This is a retrospective series of patients presenting a sausage toe on admission. Several methods were conducted to diagnose OM, and three treatment modalities were applied. Two groups were compared: acute and chronic sausage toes. Outcomes were defined as sausage toe prevalence, ulcer location, OM prevalence, and comparative treatment results. Out of 82 diabetic toe infection cases, 24 (30%) presented as 'sausage toe'. The side of the proximal interphalangeal joint of the lateral toes was the most frequent ulcer location (50%), mostly on the dorsal aspect followed by the side aspect. There were 15 (62.5%) acute cases and 9 (37.5%) chronic cases. MRI showed signs of OM in 21 (87.5%) cases and signs of septic arthritis in 3 (12.5%) cases. At the final follow-up, a successful treatment was recorded in five (20%) cases with antibiotics alone. Out of the 19 (42%) procedures, conservative surgery was performed successfully in 8 (58%) cases while amputation was needed in 11 (45.8%) cases. There was no significant difference in amputation frequency between acute and chronic groups. This is the first study documenting the sausage toe as a prevalent presentation of diabetic toe infection. The deformity is conclusive of deep infection with a very high osteomyelitis frequency. Surgery is often required for infection control and healing, mainly for chronic cases, and treatment outcomes did not differ between acute and chronic sausage toe groups. It could be beneficial to include this entity in the diabetic wound classification systems.

The Minor Phytocannabinoid Delta-8-Tetrahydrocannabinol Attenuates Collagen-Induced Arthritic Inflammation and Pain-Depressed Behaviors.

Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (Δ9-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (Δ8-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund's adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of Δ8-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The Δ8-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. Δ8-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that Δ8-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that Δ8-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis. SIGNIFICANCE STATEMENT: Despite increasing use of cannabis products, the potential effects of minor cannabinoids are largely unknown. Here, the minor cannabinoid delta-8-tetrahydrocannabinol blocked the development of experimentally induced arthritis by preventing both pathophysiological as well as functional effects of the disease model. These data support the development of novel cannabinoid treatments for inflammatory arthritis.

Sulcus-Deepening Trochleoplasty With Medial Patellofemoral Ligament Reconstruction: Outcomes at 10 to 20 Years

Background: Recent systematic reviews on the outcomes of sulcus-deepening trochleoplasty with adjuvant medial patellofemoral ligament (MPFL) reconstruction at a follow-up of 2 to 6 years have found that the procedure grants good clinical outcomes with low redislocation rates. However, there is a lack of evidence in the literature regarding mid- and long-term follow-ups. Purpose: To evaluate the radiographic and clinical outcomes of thick-flap sulcus-deepening trochleoplasty with MPFL reconstruction at a minimum follow-up of 10 years to assess the signs of patellofemoral arthritis, incidence of recurrent dislocation, and grade of patient satisfaction. Study Design: Case series; Level of evidence, 4. Methods: The authors evaluated a retrospective series of 43 patients (48 knees) who underwent sulcus-deepening trochleoplasty between 2003 and 2013. All patients underwent thick-flap sulcus-deepening trochleoplasty with additional MPFL reconstruction. All patients were assessed at a minimum follow-up of 10 years by an independent clinician who noted any patellar redislocation or reoperations in the operated knee and collected the International Knee Documentation Committee (IKDC), Kujala, and satisfaction scores. Furthermore, a radiographic examination was performed to assess patellar height using the Caton-Deschamps index and patellofemoral arthritis using the Iwano classification. Results: At a mean follow-up of 14.8 ± 2.1 years (range, 10-20 years), 4 patients (4 knees) were lost to follow-up (8.3%). The satisfaction, Kujala, and IKDC scores were 8.2 ± 1.6, 77.5 ± 14.4, and 65.7 ± 13.5, respectively. Only 1 patient reported a traumatic patellar dislocation (2%). Radiographs at the final follow-up were available for 34 knees, which revealed Iwano grade 1 in 14 knees (41%), Iwano grade 2 in 7 knees (21%), and no patellofemoral arthritis in 13 knees (38%). Conclusion: Sulcus-deepening trochleoplasty with MPFL reconstruction provides satisfactory results and prevents patellar redislocations with no or minimal patellofemoral arthritis.

Three-corner arthrodesis for scapholunate and scaphoid nonunion advanced collapsed wrists: outcomes at long term follow-ups

ObjectivesThis study aimed to assess clinical, functional and radiological outcomes after three-corner arthrodesis in patients suffering from symptomatic scapholunate or scaphoid non-union advanced collapsed wrists. We hypothesised that three-corner arthrodesis provided satisfactory clinical and radiological results in the long term. Material and methodsThis was a retrospective study of 13 patients (14 wrists) who underwent a three-corner arthrodesis between March 2004 and January 2019 with a mean follow-up of 6,7 years. Clinical assessment consisted of wrist motion, grip strength, pain and functional scores (Quick-DASH, PRWE, MWS). All complications and surgical revisions were investigated. Radiographic assessment searched for union, evaluated carpal height and ulnar translation, lunate tilt and occurrence of radio-lunate arthritis. ResultsAt the last follow-up Quick-DASH and PRWE scores were 24,87(± 17.2) and 47.4 (± 26.9) respectively and were significantly improved. Wrist motion was 35°, 32°, 10° et 24° of flexion, extension, radial and ulnar deviation respectively. Union was obtained for 13 (92,9%) wrists. The mean radiolunate angle was 11° (-17°-34°). Three patients needed reintervention, which 2 consisted of total wrist arthrodesis due to persisting pain. Mild signs of radio-lunate arthritis were found in three patients. ConclusionThree-corner arthrodesis seemed to provide satisfactory long-term functional outcomes. The union rate was high and even patients with signs of radio-lunate arthritis still had improved outcomes at the last follow-up. It could be a part of surgical options in wrists with radio- and midcarpal arthritis, among other procedures.

Identification of Risk Factors for Relapse in Childhood Leukemia Using Penalized Semi-parametric Mixture Cure Competing Risks Model.

Leukemia is the most common childhood malignancy. Identifying prognostic factors of patient survival and relapse using more reliable statistical models instead of traditional variable selection methods such as stepwise regression is of great importance. The present study aimed to apply a penalized semi-parametric mixture cure model to identify the prognostic factors affecting short-term and long-term survival of childhood leukemia in the presence of competing risks. The outcome of interest in this study was time to relapse. Study Design: A retrospective cohort study. A total of 178 patients (0‒15 years old) with leukemia participated in this study (September 1997 to September 2016, followed up to June 2021) at Golestan University of Medical Sciences, Iran. Demographic, clinical, and laboratory data were collected, and then a penalized semi-parametric mixture cure competing risk model with smoothly clipped absolute deviation (SCAD) and least absolute shrinkage and selection operator (LASSO) regularizations was used to analyze the data. Important prognostic factors of relapse patients selected by the SCAD regularization method were platelets (150000‒400000 vs.>400000; odds ratio=0.31) in the cure part and type of leukemia (ALL vs. AML, hazard ratio (HR)=0.08), mediastinal tumor (yes vs. no, HR=16.28), splenomegaly (yes vs. no; HR=2.94), in the latency part. In addition, significant prognostic factors of death identified by the SCAD regularization method included white blood cells (<4000 vs.>11000, HR=0.25) and rheumatoid arthritis signs (yes vs. no, HR=5.75) in the latency part. Several laboratory factors and clinical side effects were associated with relapse and death, which can be beneficial in treating the disease and predicting relapse and death time.

Recombinant Human Proteoglycan Aggrecan-G1 Domain-induced Arthritis (GIA) Mouse Model.

The recombinant human proteoglycan aggrecan-G1 domain (rhG1)-induced arthritis (GIA) mouse model is a complex model of rheumatoid arthritis (RA). In GIA, autoimmune arthritis is induced by repeated intraperitoneal immunization of genetically susceptible BALB/c mice with the rhG1 antigen emulsified in the adjuvant dimethyldioctadecylammonium (DDA). This article describes the steps for producing and purifying the rhG1 antigen, the immunization protocol, methods for following the clinical picture of arthritis, and the evaluation of relevant laboratory parameters. In this model, the autoimmune arthritis develops stepwise, similar to RA: First is the preclinical stage (after the first immunization, days 0-20) with no sign of inflammation but detectable T and B cell activation; next, the stage of early arthritis (after the second immunization, days 21-41), where the first definitive signs of arthritis appear together with autoantibody production; and then the severe late-stage arthritis (after the third immunization, after day 42), which presents with massive inflammation of the limbs, leading to cartilage and bone destruction and finally ankylosis. The protocols described here provide sufficient information for investigators to use the GIA model to study different aspects of autoimmune arthritis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of recombinant human proteoglycan aggrecan-G1 domain (rhG1)-induced arthritis (GIA) Support Protocol 1: Production of rhG1-Xa-mFc2a fusion protein with CHOK1 mammalian expression system Support Protocol 2: Purification of the rhG1-Xa-mFc2a fusion protein by affinity chromatography Support Protocol 3: Preparation of DDA adjuvant Support Protocol 4: Clinical assessment of arthritis Support Protocol 5: Measurement of serum antibody levels and cytokines Support Protocol 6: Measurement of rhG1-induced proliferation and cytokine production in spleen cell culture Support Protocol 7: Histological assessment of arthritic limbs Support Protocol 8: Evaluation of arthritis with micro-computed tomography.

P124 Elucidating the role of risk variants in the BIM gene enhancer in T-Cell dysregulation and rheumatoid arthritis pathogenesis

Abstract Background/Aims The balance governing T-cell responses is pivotal for immune homeostasis. Disruptions to this balance may lead to aberrant behaviours, potentially resulting in autoimmunity. Rheumatoid Arthritis (RA), an autoimmune disorder primarily manifesting in the joints, is characterised by a defective immune response, resulting in chronic inflammation. Enhanced T-cell apoptosis resistance in this context can contribute to sustained activation and abnormal proliferation in a pro-inflammatory environment. Understanding these disease mechanisms could lead to improvements in clinical care. Genome-wide association studies (GWAS) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with RA, preferentially enriched in non-coding, T-cell-specific putative enhancers. Enhancers are DNA elements that can regulate the transcription of specific genes, often from many kilobases away. Our previous work identified BCL2L11, or BIM, as the probable causal gene within the RA locus rs13396472, despite the GWAS variants' intronic positioning relative to ACOXL. The RA risk variant disrupts a distant enhancer regulating the BIM gene, pivotal for apoptosis. Given the role of apoptosis in immune tolerance, disruption of this pathway driven by RA risk variants could pave the way for autoimmune responses. Our aim was to investigate the effect of this enhancer on T-cell proliferation and function in an in vivo model. Methods We mapped the human RA-locus to the mouse genome and utilised CRISPR-Cas9 to delete this putative RA enhancer in mice. Two sgRNAs, combined with Cas9, were microinjected into C57BL6/J zygote pronuclei, followed by embryo transfer to pseudo-pregnant mice. PCR and Sanger sequencing confirmed enhancer deletion in pups, establishing an RA-enhancer deletion colony. To gauge cell proportion differences, murine splenocytes or thymocytes were stained with specific fluorochrome markers and analysed via a flow cytometer. For the antigen-induced arthritis (AIA) model, wildtype and RA-enhancer deletion mice were subjected to arthritis induction via intra-articular injection of methylated bovine serum albumin, following prior immunisation, and monitored for arthritis signs. Results We observed an increased CD4+CD8+ double positive (DP) T-cell population in aged mice homozygous and heterozygous for the RA-enhancer deletion, but not in younger and wild-type controls. Knockout mice exhibited visibly enlarged spleens in response to the immunisation step prior to AIA induction. Further work will establish the mechanisms underlying this and disease progression after arthritis induction. These observations underscore a potential impact this enhancer might have on immune responses and survival upon immune system alteration. Conclusion Our research indicates that perturbing mouse non-coding sequences syntenic to human GWAS loci can provide a physiological model to elucidate novel mechanisms underlying RA, potentially suggesting therapeutic targets. Future research will explore the mechanism by which the enhancer deletion leads to an increase in DP T-cells and the altered phenotype, and the implications of such a change for T- and B-cell biology and RA. Disclosure S. Rossi: None. E. Richards: None. J. Ding: None. C. Shi: None. M. Menon: None. J. Gibbs: None. R. Grencis: None. A. Adamson: None. G. Orozco: None.

Elevated levels of anti-Golgi antibodies: An early sign of seronegative rheumatoid arthritis.

Anti-Golgi antibodies are uncommon antibodies that exhibit specific, polarized cytoplasmic staining on the Hep-2 substrate. The objective of our study was to identify the clinical and laboratory features associated with anti-Golgi antibodies. We examined 4.5 years of data from a Turkish tertiary hospital in this retrospective cohort analysis. The indirect immunofluorescence staining patterns, antinuclear antibody (ANA) titres and clinical data of all patients were obtained from the hospital record system. A total of 146,055 ANAs were detected, of which 224 patients (0.15%) exhibited anti-Golgi antibody staining. In total, 39.4% of diagnosed patients had autoimmune diseases (AIDs). Of the AIDs, 26 (46.4%) were rheumatoid arthritis (RA). This is a very high rate and another remarkable point is that 17 (65.3%) of these patients had seronegative RA. High-titre results (1 ≥ 1/320) were more common in patients with AID. Anti-Ro52 was prevalent in 50% of extractable nuclear antigen (ENA)-positive patients, making it a remarkable finding. The majority of individuals with high-titre anti-Golgi antibodies had AID, particularly RA. The majority of these patients also tested negative for anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF). Finally, high-titre anti-Golgi antibodies may be an important serologic marker for seronegative RA in the Turkish population.

Novel mechanistic study of HDAC6 regulation of rheumatoid arthritis via CMA: exploring potential therapeutic targets.

Rheumatoid arthritis (RA) is a systemic autoimmune disease. Its pathogenesis has not yet been clarified, so it is urgent to explore therapeutic targets. Here, we clarified the role of HDAC6 in the mechanism of action of RA through mediating chaperone-mediated autophagy (CMA) to provide a clinical treatment of RA. We used rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis mice (CIA mice) as models of RA and pharmacological inhibitors as well as genetic interference with adeno-associated viruses to reduce the expression of HDAC6. We explored the influence of CAY10603 on RA-FLS proliferation and inflammation, as well as the expression of proteins related to the CMA signaling pathway. CIA model was constructed using DBA/1J mice. Arthritis symptoms in CIA mice were evaluated, and the expression and localization of CMA-related proteins in mouse ankle joints were examined. CAY10603 inhibited proliferation as well as the level of the molecular chaperone autophagy in RA-FLS. HDAC6 shRNA significantly reduced the clinical signs of arthritis in CIA mice, as did the expression of HDAC6 in the serum and ankle synovial tissues of CIA mice. Finally, it significantly inhibited the level of Hsc70 and LAMP-2A, which are involved in the CMA signaling pathway, in ankle joint tissues. Downregulation of HDAC6 may inhibit CMA and thereby ameliorate RA.

Clinical study to Evaluate Safety and Efficacy of Boozidaan (Pyrethrum indicum) in the management of Niqris Muzmin (Chronic Gout)

Objectives: The objectives of this study were to observe the Efficacy of unani pharmacopoeial formulation Boozidan (Pyrethrum indicum) for the management of Niqris Muzmin (Chronic gout) and to observe any concomitant and adverse effects of formulation.&#x0D; Methods: This single blind, randomized and standard control clinical study was conducted between April 2021 to October 2021 for a period of 28 days. 60 patients diagnosed with chronic gout were divided into two groups, 30 Test group and 30 Control group. The test group was administered with 5g boozidaan in powder form once daily with water and the patients of control group were given tablet febuxostat 80mg once daily. Patients were followed up and improvements in subjective parameters were assessed weekly at 7th, 14th, 21st, and 29th day. Objective parameters were assessed at the baseline and at 29th day. The data obtained was subjected to statistical analysis.&#x0D; Results: Both the test and control drug were effective in reducing Serum uric acid level, ESR and CRP levels. A significant improvement in subjective and objective parameters was observed in both test and control groups and no adverse effects were observed during and after the study.&#x0D; However, the test drug had superior efficacy in reducing the objective parameters and it was statistically significant (p-value&lt;0.0001).&#x0D; Conclusion: Both Boozidaan and Febuxostat were safe and significantly effective in resolving the symptoms and signs of gouty arthritis and both have significant effect on reducing serum uric acid level.&#x0D; Keywords: Boozidaan, Chronic gout, Niqris, Febuxostat, serum uric acid, unani medicine

Kinematic stabilization after the Latarjet procedure: beyond the triple blocking effect

BackgroundThe rationale for the Latarjet procedure was described as the “triple blocking” effect. Satisfactory surgical outcomes have been reported after surgery. However, it has been reported that the “triple blocking” effect increases joint stability, but it does not fully restore it. Moreover, the procedure is nonanatomic and concerns remain regarding the effects. The study of scapulohumeral rhythm, which is a clinical parameter used for the functional evaluation of shoulder kinematics, can offer new perspectives on the rationale for the procedure. This study aimed to compare the shoulder kinematics of patients after the Latarjet procedure to the shoulders of a healthy population using magnetic and inertial measurement units (MIMUs) with a motion analysis system. MethodsA retrospective study with prospective data collection was conducted on 28 patients who underwent the open Latarjet procedure for recurrent shoulder instability. At a minimum 12-month follow-up, each patient was evaluated by assessing the range of motion (ROM), the Rowe score, and the Constant-Murley score (CMS). Patients were examined using the ShowMotion 3D kinematic tracking system (NCS Lab, Modena, Italy), which uses wireless wearable noninvasive MIMUs sensors to assess the three-dimensional kinematics of the shoulder. For each plane of elevation (i.e., flexion and abduction), the scapulohumeral rhythm (SHR) was described by three scapulothoracic rotations (i.e., protraction–retraction, mediolateral rotation and posterior–anterior tilting) as a function of humeral anteflexion or humeral abduction. ResultsThe mean time from first shoulder dislocation to surgery was 6.6 ± 3 years (range, 1-12 years). No intraoperative complications occurred, and CT performed 3 months after surgery showed graft union in all patients. After a mean follow-up time of 32.4±20 months (range, 12-96), the mean CMS and Rowe scores were 94.5±4.8 (range, 84-100) and 96.7±3.5 (range, 90–100), respectively. All patients showed no signs of glenohumeral arthritis on X-ray examination. Scapular posterior tilt and scapular internal rotation were significantly greater in the patient group than in the healthy population for the flexion–extension and abduction–adduction movements along the whole shoulder range of motion (all p < 0.05); no differences were found in upward/downward scapular rotation. ConclusionA greater scapular posterior tilt and scapular internal rotation were observed after the Latarjet procedure. The modified position of the scapula was maintained during the entire ROM, suggesting a shoulder-stabilizing kinematic effect in addition to the bony, sling and bumper effects.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Psoriatic Arthritis Involving TMJ: A Review on Pathogenesis and Consideration on Eventual Gender Differences.

Psoriatic arthritis is defined as chronic inflammatory arthritis associated with psoriasis. The current data regarding gender differences in clinical manifestation and therapeutic outcomes of psoriatic arthritis are limited. Generally, men show a peripheral disease manifestation, while women have an axial distribution of the lesions. If we look at temporomandibular joint (TMJ) involvement, epidemiological data on the involvement of the TMJ are hard to find. Few studies on therapeutic management and the related impact on the quality of life are reported in the literature. Given the morpho-functional peculiarities of the TMJ and the different pain burdens between male and female genders, when manifestation of psoriatic arthritis occurs, clinicians should face it using a multidisciplinary approach for a correct diagnosis and successful treatment. This review aims to examine the diagnostic signs of psoriatic arthritis in the TMJ, the eventual variations of this disease in male and female patients, and the therapeutical strategies. The coordination of different specialties is fundamental to the remission of clinical symptoms and lesion regression.

Amino Acids Fueling Fibroblast-Like Synoviocyte Activation and Arthritis By Regulating Chemokine Expression and Leukocyte Migration.

We analyzed the impact of amino acid (AA) availability on the inflammatory response in arthritis. We stimulated rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) with tumor necrosis factor (TNF) in the presence or absence of proteinogenic AAs and measured their response by QuantSeq 3' messenger RNA sequencing, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. Signal transduction events were determined by Western blot. We performed K/BxN serum transfer arthritis in mice receiving a normal and a low-protein diet and analyzed arthritis clinically and histologically. Deprivation of AAs decreased the expression of a specific subset of genes, including the chemokines CXCL10, CCL2, and CCL5 in TNF-stimulated FLSs. Mechanistically, the presence of AAs was required for the TNF-induced activation of an interferon regulatory factor 1 (IRF1)-STAT1 signaling circuit that drives the expression of chemotactic factors. The expression of IRF1 and the IRF1-dependent gene set in FLSs was highly correlated with the presence of inflammatory cells in human RA, emphasizing the important role of this AA-dependent pathway in inflammatory cell recruitment to the synovial tissue. Finally, we show that mice receiving a low-protein diet expressed less IRF1 in the inflamed synovium and consequently developed reduced clinical and histologic signs of arthritis. AA deprivation reduces the severity of arthritis by suppressing the expression of IRF1-STAT1-driven chemokines, which are crucial for leukocyte recruitment to the arthritic joint. Overall, our study provides novel insights into critical determinants of inflammatory arthritis and may pave the way for dietary intervention trials in RA.