Joint Destruction Research Articles

Tubercular arthritis of the elbow mimicking as a neoplasm: a case report and literature review

Tuberculous arthritis of the elbow joint is rare. A 38-year-old male patient presented with swelling, pain, and deformity of the elbow. The symptoms first appeared one year ago; he was clinic-radiologically evaluated and diagnosed with neoplasm. The patient underwent biopsy to confirm the diagnosis and was found to have tuberculous arthritis and was started on anti-tubercular treatment and underwent surgical debridement. Tuberculous arthritis usually presents with chronic arthritis. However, it can also present in patients with septic arthritis. If untreated, it can cause joint destruction. Hence, early diagnosis and treatment is important.

Essential Fatty Acids and Osteoarthritis.

Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.

Protective effects of piperlongumine against adjuvant-induced arthritis in rats through modulating OPG/RANKL/NF-κB signaling pathway.

We examined the antirheumatoid effects of piperlongumine (PLM) on rat adjuvant-induced arthritis (AIA) and explored the underlying mechanisms involved. PLM (2.5, 5, and 10 mg/kg) was administered intraperitoneally to AIA rats to assess its effectiveness. Blood, thymus, spleen, ankle joint, and synovial tissue samples were gathered for subsequent analyses, like enzyme-linked immunosorbent assay, thymus/spleen index measurement, ankle joint pathological examination, immunohistochemistry assay, polymerase chain reaction, and western blot assay. Moreover, the involvement of osteoprotegerin (OPG)/receptor activators of nuclear factor κB ligand (RANKL)/nuclear factor-κB (NF-κB) signaling was investigated. PLM effectively relieved inflammation and joint destruction in AIA rats, as indicated by reductions in hind paw swelling, arthritis index, thymus/spleen index, ankle joint pathological damage, production of TNF-α, IL-1β, and IL-6 in both serum and synovium, and osteoclast formation. Also, PLM treatment raised OPG production, reduced RANKL expression, and elevated the OPG/RANKL ratio in synovial tissues. Furthermore, PLM prevented IκBα degradation and phosphorylation, resulting in a reduced expression of the nuclear NF-κB p65 protein in AIA rat synovial tissues. PLM demonstrated strong antiarthritic effects in rats with AIA by influencing the OPG/RANKL/NF-κB signaling pathway, highlighting its potential clinical relevance in treating rheumatoid arthritis.

Network Pharmacology and Experimental Verifications to Discover Scutellaria baicalensis Georgi's Effects on Joint Inflammation, Destruction, and Pain in Osteoarthritis.

Osteoarthritis is the most common type of arthritis, characterized by joint pain and a decline in physiological function. Scutellaria baicalensis Georgi (SB) is potentially effective against osteoarthritis because of its wide range of anti-inflammatory pharmacological activities. This study aimed to identify the mode of action of SB against osteoarthritis using network pharmacology prediction and experimental verification. Networks were constructed to key compounds, hub targets, and pathways essential for SB's effectiveness against osteoarthritis. Additionally, in vivo and in vitro tests were performed, including investigations on weight bearing in hind limbs, the acetic acid-induced writhing response, lipopolysaccharide-stimulated RAW264.7 cells, and serum cytokine responses. We identified 15 active compounds and 14 hub targets, supporting the anti-osteoarthritis effects of SB. The Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that fluid shear stress, atherosclerosis, phosphatidylinositol 3-kinase-Akt signaling, and cellular senescence pathways were important. SB showed substantial anti-inflammatory, analgesic, and joint tissue-protective effects against osteoarthritis. Our study shows that SB has the potential value to be further investigated as a candidate material for the treatment of osteoarthritis in the future.

Influence of periodontal treatment on rheumatoid arthritis clinical parameters

Periodontitis is a common chronic inflammatory disease characterized by destruction of tooth-supporting tissues, including alveolar bone, periodontal ligament, and cementum. It is the leading cause of dental loss and is considered one of the two biggest threats to oral health (Zhao et al., 2018). Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by swelling of the joints, joint tenderness, and destruction of the synovial joints, leading to severe incapacitation and premature mortality as it involves systemic effects. Both have been related, because the severity of RA is greater in patients with the first disease (Mercado et al., 2001) and Porphyromonas gingivalis, is also identified in synovial fluid and not only in damaged periodontal tissue. The proposed research was a prospective clinical trial with a quantitative approach carried out in the dental clinic of UNIOESTE in 90 days with 20 patients suffering from the autoimmune disease. Improvements in the disease were noted by means of analysis by the T, DAS 28 and VAS tests when the periodontal suitability was chosen.

Pathophysiology and Management of Refractory Rheumatoid Arthritis: A Narrative Literature Review

Refractory rheumatoid arthritis is rheumatoid arthritis that fails to achieve low levels of disease activity using 2-3 DMARDS treatment and at least one other first-line bDMARD. The definition of refractory action is based on the number of failed DMARDs, the scale of the problem, and risk factors for a refractory disease course. Until now, there has been no further research discussing the pathophysiology of refractory RA, but it is known that TNF-α, IL-6, and IL-1 are the most important mediators that enable cell migration and inflammation in RA. IL-6 in particular, acts directly on neutrophils, which then contribute to inflammation and joint destruction by secreting proteolytic enzymes. The main goal to be achieved in RA is remission, low disease activity and an alternative goal for those who fail to achieve therapy targets. Currently, there are several bDMARD agents that can be used as therapy for refractory RA, namely TNF alfa inhibitors, B cell depletion agents, T cell activity inhibitors, and cytokine inhibitors.

Anti-sclerostin antibody therapy prevents post-ischemic osteonecrosis bone collapse via interleukin-6 association

Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by subchondral bone necrosis, which frequently culminates in joint destruction. Although total hip arthroplasty is conventionally practiced to remediate ONFH, for patients under the age of 60, the outcomes can be suboptimal. Chronic inflammation, particularly that mediated by interleukin-6 (IL-6), has been conjectured to be a potential mechanism underlying the etiology of ONFH. This study aimed at exploring the interplay between IL-6, the canonical Wnt signaling pathway, and ONFH to provide insights for potential therapeutic interventions. Human ONFH specimens depicted an elevation in β-catenin expression in the transitional layer, while IL-6 levels were pronounced in the same region. Subsequently, mouse models of ischemic osteonecrosis were treated with an anti-sclerostin antibody to assess its effects on bone metabolism and cellular processes. Histological analysis revealed that the administration of anti-sclerostin antibodies effectuated early recovery from bone necrosis, reduced empty lacunae, and suppressed IL-6 expression. The treatment evidently initiated the activation of the Wnt/β-catenin signaling pathway, presenting a potential mechanism associated with IL-6-mediated inflammation. Furthermore, the antibody upregulated osteoblast formation, downregulated osteoclast formation, and increased bone volume. Micro-CT imaging demonstrated increased bone volume, prevented epiphyseal deformity, and improved compression strength.Therefore, this study yields significant findings, indicating the potency of anti-sclerostin antibodies in effectively modulating the Wnt/β-catenin pathway, associating with IL-6 expression, and preventing post-ONFH bone collapse. Additionally, this preclinical investigation in mouse models offers an avenue for prospective research on potential therapeutic interventions against human ONFH.

Human Umbilical Cord Mesenchymal Stem Cells Alleviate Rat Knee Osteoarthritis via Activating Wnt/ β-catenin Signaling Pathway.

Osteoarthritis (OA) is a chronic disease characterized by joint cartilage degeneration, destruction, and osteogenic hyperplasia. Human umbilical cord mesenchymal stem cells (hUCMSCs) have attracted increasing research interest due to their high clonogenic, proliferative, and migratory potential, as well as their improved secretion of relevant chondrogenic factors. This study evaluated the therapeutic potential and underlying mechanism of hUC-MSCs in alleviating pathological symptoms of OA. For the in vivo study, OA rats were established by the Hulth method to observe the therapeutic effect of intra-articular injection of hUC-MSCs. X-ray tests, gross observations, and histological and immunohistochemical assessments were conducted in rats. Levels of interleukin-1 beta (IL-1β), IL-6, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor matrix metalloproteinase-1 in rats' synovial fluid were measured using enzyme-linked immunosorbent assay kits. For the in vitro study, hUC-MSCs and chondrocytes were cultured to explore the effect and underlying mechanisms of hUC-MSCs on OA. Apoptosis, proliferation, and glycosaminoglycan (GAG) were measured in the chondrocytes. The relative expression of aggrecan, COL-2, and SOX-9 mRNA was quantified by real-time polymerase chain reaction. Expressions of Wnt/β-catenin signaling molecules were measured by Western blot. We found that intra-articular injection of hUC-MSCs reduced the combined score, increased the expression of collagen II, and decreased the expression of MMP-13, IL-1β, and IL-6 in rat knee joints. Additionally, hUC-MSCs increased the content of GAGs, inhibited chondrocyte apoptosis, and promoted chondrocyte proliferation. The expression of aggrecan, COL-2, and SOX-9 mRNA in chondrocytes was promoted by hUC-MSCs via activation of the Wnt/β-catenin signaling pathway. Overall, this study demonstrated that hUC-MSCs induce the secretion of some cytokines via the paracrine function to activate the Wnt/β-catenin signaling pathway to reduce the pathological condition of OA and maintain the proper expression of cytokines and extracellular matrix proteins.

The parasitic worm product ES-62 protects against collagen-induced arthritis by resetting the gut-bone marrow axis in a microbiome-dependent manner.

The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62's prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220+ and CD3+ cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62's ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62's targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62's actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice.

DIAGNOSTIC ACCURACY OF X-RAY IN DIAGNOSING AVASCULAR FEMORAL HEAD, KEEPING MAGNETIC RESONANCE IMAGING (MRI) AS GOLD STANDARD

Avascular necrosis of the femoral head is a common cause of musculoskeletal disability, and it presents a significant diagnostic and therapeutic challenge. Although patients are initially asymptomatic, avascular necrosis frequently leads to joint destruction, typically before the age of 50. Magnetic Resonance Imaging (MRI) is a non-invasive, rapid, and compassionate diagnostic tool commonly used by clinicians. This study aims to determine the diagnostic accuracy of X-rays in detecting avascular necrosis of the femoral head, using MRI as the gold standard. This Cross-Sectional Validation Study was conducted at the Department of Radiology, JPMC, Karachi, Pakistan. The study was conducted over six months after the synopsis approval, from November 6, 2021, to May 5, 2022. This study included all patients who met the inclusion criteria and visited the JPMC Hospital in Karachi. After explaining the procedure, risks, and benefits of the study, informed consent was obtained from all patients. All patients underwent X-rays, and those diagnosed with avascular necrosis of the femoral head underwent MRI. The collected data was entered into the attached proforma and used electronically for research. The mean age was 48.8±9.2, with 92 (63.0%) male and 54 (37.0%) female patients. The diagnostic accuracy of the X-ray was 82.88% in detecting avascular necrosis of the femoral head, with sensitivity and specificity of 82.05% and 83.82%, respectively. The positive predictive value (PPV) was 53.42%, and the negative predictive value (NPV) was 80.28%, using MRI findings as the gold standard. In conclusion, the use of X-ray in evaluating avascular necrosis of the femoral head was not helpful and comparable to MRI. Therefore, an MRI should be performed in every case of avascular necrosis of the femoral head to achieve an accurate diagnosis. More prospective and well-controlled trials are required to validate the current findings.

Emerging Phytochemical Formulations for Management of Rheumatoid Arthritis: A Review.

Rheumatoid arthritis (RA) is a T-cell-mediated chronic inflammatory disorder affecting 0.5-1% of the global population. The disease with unknown etiology causes slow destruction of joints, advancing to significant deterioration of an individual's quality of life. The present treatment strategy comprises the use of disease-modifying anti-rheumatic drugs (DMARDs) coupled with or without nonsteroidal anti-inflammatory drugs or glucocorticoids. Additionally, involves co-therapy of injectable biological DMARDs in case of persistent or recurrent arthritis. The availability of biological DMARDs and the implementation of the treat-to-target approach have significantly improved the outcomes for patients suffering from RA. Nevertheless, RA requires continuous attention due to inadequate response of patients, development of tolerance and severe side effects associated with long-term use of available treatment regimens. An estimated 60-90% of patients use alternative methods of treatment, such as herbal therapies, for the management of RA symptoms. Over the past few decades, researchers have exploring natural phytochemicals to alleviate RA and associated symptoms. Enormous plant-origin phytochemicals such as alkaloids, flavonoids, steroids, terpenoids and polyphenols have shown anti-inflammatory and immunomodulatory activity against RA. However, phytochemicals have certain limitations, such as high molecular weight, poor water solubility, poor permeability, poor stability and extensive first-pass metabolism, limiting absorption and bioavailability. The use of nanotechnology has aided to extensively improve the pharmacokinetic profile and stability of encapsulated drugs. The current review provides detailed information on the therapeutic potential of phytochemicals. Furthermore, the review focuses on developed phytochemical formulations for RA, with emphasis on clinical trials, regulatory aspects, present challenges, and future prospects.

A Case Report on Avascular Necrosis of Right Femoral Head in a 20-years Old Male

Avascular necrosis of the femoral head is a condition which causes cellular destruction of bone material due to interruption of blood supply. Necrosis is caused by inadequate blood supply, resulting in bone tissue destruction with collapsing of that segment. The disease usually occurs in young adults, and femoral head is one of the commonest sites. Avascular necrosis may be traumatic or non-traumatic and causes major musculoskeletal disability. Initially patients remain asymptomatic. In untreated cases the disease progresses and causes joint destruction, requiring surgical intervention and in later stages need total hip replacement. Plain X-ray, isotope bone scan and magnetic resonance imaging (MRI) play important role in making the diagnosis. MRI is highly accurate method for the diagnosis of avascular necrosis of the femoral head.

Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain.

Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1β, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-β. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation.

The Hepatokine RBP4 Links Metabolic Diseases to Articular Inflammation.

This study investigates the role of retinol binding protein 4 (RBP4) in an articular context. RBP4, a vitamin A transporter, is linked to various metabolic diseases. Synovial fluid RBP4 levels were assessed in crystalline arthritis (CA) patients using ELISA. RBP4's impact on articular cell types was analysed in vitro through RT-PCR and flow cytometry. Proteomic analysis was conducted on primary human osteoarthritis chondrocytes (hOACs). Synovial fluid RBP4 concentrations in CA patients correlated positively with glucose levels and negatively with synovial leukocyte count and were elevated in hypertensive patients. In vitro, these RBP4 concentrations activated neutrophils, induced the expression of inflammatory factors in hOACs as well as synoviocytes, and triggered proteomic changes consistent with inflammation. Moreover, they increased catabolism and decreased anabolism, mitochondrial dysfunction, and glycolysis promotion. Both in silico and in vitro experiments suggested that RBP4 acts through TLR4. This study identifies relevant RBP4 concentrations in CA patients' synovial fluids, linking them to hypertensive patients with a metabolic disruption. Evidence is provided that RBP4 acts as a DAMP at these concentrations, inducing robust inflammatory, catabolic, chemotactic, and metabolic responses in chondrocytes, synoviocytes, and neutrophils. These effects may explain RBP4-related metabolic diseases' contribution to joint destruction in various rheumatic conditions like CA.

Lipid mediators obtained from docosahexaenoic acid by soybean lipoxygenase attenuate RANKL-induced osteoclast differentiation and rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by persistent inflammation and joint destruction. A lipid mediator (LM, namely, 17S-monohydroxy docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50) produced by soybean lipoxygenase from DHA, exhibits anti-inflammatory activity. In this study, we determined the effect of LM on collagen antibody-induced arthritis (CAIA) in mice and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in RAW264.7 cells. LM effectively downregulated the expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K, inhibited osteoclast formation, and suppressed the NF-κB signaling pathway in vitro. In vivo, LM at 10 μg/kg/day significantly decreased paw swelling and inhibited progression of arthritis in CAIA mice. Moreover, proinflammatory cytokine (tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-17, and interferon-γ) levels in serum were decreased, whereas IL-10 levels were increased following LM treatment. Furthermore, LM alleviated joint inflammation, cartilage erosion, and bone destruction in the ankles, which may be related to matrix metalloproteinase and Janus kinase (JAK)–signal transducer and activators of transcription (STAT) signaling pathway. Our findings suggest that LM attenuates arthritis severity, restores serum imbalances, and modifies joint damage. Thus, LM represents a promising therapy for relieving RA symptoms.

Cartilage destruction in early rheumatoid arthritis patients correlates with CD21−/low double-negative B cells

BackgroundInvolvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction.MethodsSeventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry.ResultsCompared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27−IgD−) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL).ConclusionsCartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.

Influence of streptococcal infection on the appearance of caries in the background of chronic rheumatoid arthritis and the transmitted coronavirus infection COVID-19 (literature review)

Relevance. Caries of hard dental tissues is one of the most common diseases throughout the world. It affects not only the primary teeth of children, but also the permanent teeth of adults, which can lead to serious consequences for human health. In recent years, the dental community has paid special attention to the possible connection between streptococcal infection and the development of caries, and therefore this topic is extremely relevant and requires detailed consideration. Chronic rheumatoid arthritis (CRA) is one of the most common joint diseases, which is characterized by inflammation of the joint lining and destruction of cartilage. Patients with CPA are also at high risk of developing dental caries, which may be due to many factors, including changes in saliva composition and long-term use of medications.Purpose of the study: to study the effect of streptococcal infection on the occurrence of caries among patients suffering from chronic rheumatoid arthritis. To assess the incidence of caries complications caused by streptococcal infection among patients who have had COVID-19.Materials and methods of research. The authors analyzed domestic and foreign literature in order to conduct a literature review regarding the etiology of the occurrence and relationship of streptococcal infection and caries against the background of rheumatoid arthritis. The authors also analyze the incidence of caries complications caused by streptococcal infection as a consequence of COVID-19. Data from 160 patients, 100 men and 60 women, were studied.Conclusion. From the studies conducted, we can conclude that streptococcal infection is one of the factors influencing the development of caries. However, the exact mechanisms of interaction between bacteria and hard dental tissues have not yet been established. As a result of the analysis, it was revealed that the relationship between streptococcal infection and the occurrence of caries against the background of chronic rheumatoid arthritis is significant. The presence of streptococcal infections in patients with rheumatoid arthritis can lead to deterioration of oral health, which in turn contributes to the development of dental caries. Among patients who have had COVID-19, there is a fairly high percentage of caries, including those caused by streptococcal infection and a general deterioration in the health of the oral cavity and the body as a whole.

Demographic, Clinical Profile of Rheumatoid Arthritis Patients and Their Association with Disease Severity in Ghana.

Rheumatoid arthritis (RA) is one of the frequent chronic, systemic, inflammatory autoimmune disorders with an estimated global prevalence of 1%. RA leads to joint destruction and disability if left untreated. Ghana has seen very few studies on RA, and little is known about the disease's severity and related variables. This study sought to characterize the clinical presentation and determine disease severity and associated risk factors with disease severity among RA patients in a tertiary hospital in Ghana. This cross-sectional study was conducted between September 2020 and August 2021. This study included 56 consecutively consenting RA patients from the Komfo Anokye Teaching Hospital orthopaedic unit. Diagnosis of RA was based on the updated American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2022 rheumatoid arthritis classification criteria by a rheumatologist. A study questionnaire was used to gather participant demographics and clinical features, and results from the laboratory were taken from the patients' charts and medical records. The patients' disease severity was evaluated based on the rheumatoid arthritis disease activity score, which is based on a 28-joint count (DAS28), and their functioning was evaluated using the modified health assessment questionnaire. The participants' mean age was 51.25 ± 13.22 years. Out of the total participants, 46 were females, and 10 were males (female-to-male ratio 4.6 : 1). Moreover, 37.50% had arthritis of the hand; 5.30% had severe disease, and 94.60% were not severe. A majority (76.80%) were on methotrexate medication. The most frequently involved joints were the knee (42.90%), wrist (32.10%), and elbow (12.50%). There was no statistically significant association with disease severity and a functional status score of >0.5 (cOR: 10.60, 95% CI (0.52-217.30); p = 0.124). In addition, marital status (p = 0.04), disease duration (p = 0.04), family complaints (p = 0.02), and ESR (p = 0.03) were significantly associated with disease severity. RA is predominant among elder populations and females. Disease duration, family complaints, and ESR are associated with disease severity. The findings of this study call for interventions towards ensuring early diagnosis of RA among high-risk populations to enhance good management practices.

Intra-articular injection of stigmasterol-loaded nanoparticles reduce pain and inhibit the inflammation and joint destruction in osteoarthritis rat model: A pilot study.

Stigmasterol, a plant-derived sterol, sharing structural similarity with cholesterol, has demonstrated anti-osteoarthritis (OA) properties, attributed to its antioxidant and anti-inflammatory capabilities. Given that OA often arises in weight bearing or overused joints, prolonged localized treatment effectively targets inflammatory aspects of the disease. This research explored the impact of stigmasterol-loaded nanoparticles delivered via intra-articular injections in an OA rat model. Employing mesoporous silica nanomaterials (MSNs) combined with β-cyclodextrin (β-CD) as a vehicle, stigmasterol was loaded in conjunction with tannic acid, forming stigmasterol/β-CD-MSNs to facilitate a sustained stigmasterol release. The study employed RAW 264.7 cells to examine the in vitro cytotoxicity and anti-inflammatory effect of stigmasterol/β-CD-MSNs. For in vivo experimentation, we used healthy control rats and monosodium iodoacetate (MIA)-induced OA rats, separated into five groups, varying the injection substances. In vitro findings indicated that stigmasterol/β-CD-MSNs suppressed the mRNA expression of key pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-3 in a dose-dependent manner. In vivo experiments revealed a substantial decrease in the mRNA levels of pro-inflammatory factors in the stigmasterol(50µg)/β-CD-MSN group compared to the others. Macroscopic, radiographic, and histological evaluations established that intra-articular injections of stigmasterol/β-CD-MSNs inhibited cartilage degeneration and subchondral bone deterioration. Therefore, in a chemically induced OA rat model, intra-articular stigmasterol delivery was associated with reduction in both local and systemic inflammatory responses, alongside a slowdown in joint degradation and arthritic progression.

Cathepsin B serves as a potential prognostic biomarker and correlates with ferroptosis in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a long-term, systemic, and progressive autoimmune disorder. It has been established that ferroptosis, a type of iron-dependent lipid peroxidation cell death, is closely associated with RA. Fibroblast-like synoviocytes (FLS) are the main drivers of RA joint destruction, and they possess a high concentration of endoplasmic reticulum structure. Therefore, targeting ferroptosis and RA-FLS may be a potential treatment for RA. MethodsFour machine learning algorithms were utilized to detect the essential genes linked to RA, and an XGBoost model was created based on the identified genes. SHAP values were then used to visualize the factors that affect the development and progression of RA, and to analyze the importance of individual features in predicting the outcomes. Moreover, WGCNA and PPI were employed to identify the key genes related to RA, and CIBERSORT was used to analyze the correlation between the chosen genes and immune cells. Finally, the findings were validated through in vitro cell experiments, such as CCK-8 assay, lipid peroxidation assay, iron assay, GSH assay, and Western blot. ResultsBioinformatics and machine learning were employed to identify cathepsin B (CTSB) as a potential biomarker for RA. CTSB is highly expressed in RA patients and has been found to have a positive correlation with macrophages M2, neutrophils, and T cell follicular helper cells, and a negative correlation with CD8 T cells, monocytes, Tregs, and CD4 memory T cells. To investigate the effect of CTSB on RA-FLS from RA patients, the CTSB inhibitor CA-074Me was used and it was observed to reduce the proliferation and migration of RA-FLS, as indicated by the accumulation of lipid ROS and ferrous ions, and induce ferroptosis in RA-FLS. ConclusionsThis study identified CTSB, a gene associated with ferroptosis, as a potential biomarker for diagnosing and managing RA. Moreover, CA-074Me, a CTSB inhibitor, was observed to cause ferroptosis and reduce the migratory capacity of RA-FLS.