Acetaminophen (APAP), or paracetamol, is one of the most widespread and commonly used non-prescription pain medication in the world, and is effective at managing wide range of pain, including headache, muscle ache, and minor arthritic pain. While the pharmacokinetics of APAP is generally understood, there is a lack of data for its transfer ratio especially into the knee. A novel multi-microdialysis model was developed to simultaneously sample from blood, forelimb extensor muscle, brain striatum, and the knee joint cavity in the same experimental subject to investigate the potential interaction between APAP and Achyranthes bidentata Blume (A. bidentata), another widely used traditional Chinese medicininal herb especially for pain in the lower extremity. Rats were pre-treated with A. bidentata extract (ABex), APAP was then administered (60 mg/kg, i.v.), dialysates then subsequently analyzed using HPLC-PDA. Our analysis demonstrated that APAP concentrations, achieved after its administration either alone or in combination with ABex (1 and 3 g/kg, q.d. gavage), could be modelled effectively with a one-compartment model. The distribution ratio (AUCorgan/AUCblood) of blood-to-muscle, blood-to-brain and blood-to-knee was 0.372 ± 0.053, 0.277 ± 0.095 and 0.191 ± 0.042, respectively after administration of APAP (60 mg/kg, i.v.). No significant difference was observed between the pharmacokinetics of APAP administered alone and in combination with ABex; and APAP concentration exceed the half maximal effective concentration (EC50) in all sampled organs for close to 3 hours with one single dose of drug administration, providing evidence for its broad-range analgesic effect.

Lipid metabolism factors may play a role in the development of arthritis and hepatic steatosis and fibrosis. The aim of this study was to explore the potential association between arthritis and hepatic steatosis and liver fibrosis.
The nationally representative sample from the National Health and Nutrition Examination Survey was analyzed, with data on arthritis diagnosis, subtype, and liver status obtained. Liver status was assessed using transient elastography. Hepatic steatosis was defined as a Controlled Attenuation Parameter (CAP) score ≥263 dB/m, and liver fibrosis status was defined as F0‒F4. Logistic regression models and subgroup analyses stratified by sex were used to evaluate the associations. Smooth curve fitting was used to describe the associations.
The present study of 6,840 adults aged 20 years or older found a significant positive correlation between arthritis and CAP in multivariate logistic regression analysis (β = 0.003, 95 % CI 0.001 to 0.0041, p < 0.001). Participants with arthritis had a higher risk of hepatic steatosis (OR = 1.248, 95 % CI 1.036 to 1.504, p = 0.020), particularly those with osteoarthritis or degenerative arthritis, but not rheumatoid arthritis (p = 0.847). The positive correlation was maintained in females (β = 0.004, 95 % CI 0.002 to 0.006, p < 0.001), but not in males. There was no significant relationship between arthritis and liver fibrosis (p = 0.508).
This study indicates that there is a positive correlation between arthritis and hepatic steatosis, particularly in females. Nonetheless, there is no significant relationship between arthritis and the risk of liver fibrosis.

BACKGROUND: Research has highlighted the role of runt-related transcription factor 2 (Runx2) in the development of osteoarthritis (OA); however, its causal association remains unclear. This study aimed to explore whether Runx2 expression is causally associated with OA and assess its therapeutic potential for OA.
METHODS: Genetic proxy instruments for Runx2 expression were obtained from gene expression quantitative trait locus (eQTLs) study of eQTLGen Consortium (n = 31,684). Aggregated genome-wide association study (GWAS) data for OA (including all OA [177,517 cases and 649,173 controls], knee OA (KOA) [62,497 cases and 333,557 controls], and hip OA (HOA) [36,445 cases and 316,943 controls]) were extracted from the Genetics of Osteoarthritis Consortium. We integrated eQTLs data with OA GWAS data to estimate their causal association and to estimate the potential of Runx2 as a drug target in the treatment of OA using summary data-based Mendelian randomization (SMR) analysis. Furthermore, different OA GWAS data (including all OA [77,052 cases and 378,169 controls], KOA [24,955 cases and 378,169 controls], and HOA [15,704 cases and 378,169 controls]) derived from the GWAS Catalog database were used for replication study.
RESULTS: SMR analysis showed that high expression levels of Runx2 were associated with an increased risk of all OA [odds ratio (OR) 1.044, 95% confidence interval (CI) 1.023-1.067; P = 5.03 × 10-5], KOA (OR 1.040, 95% CI 1.006-1.075; P = 0.021), and HOA (OR 1.067, 95% CI 1.022-1.113; P = 0.003). This suggests that Runx2 inhibitors may have promising potential for the treatment of OA. Notably, the causal effects of Runx2 with all OA (OR 1.053, 95% CI 1.027-1.079; P = 3.95 × 10-5) and KOA (OR 1.043, 95% CI 1.001-1.087; P = 0.045) were repeated in the replication study, but limited evidence supported the association of Runx2 expression levels with HOA (OR 1.045, 95% CI 0.993-1.101; P = 0.094).
CONCLUSIONS: Our analyses indicate a positive correlation between Runx2 expression and OA risk across all three phenotypes, suggesting the potential of Runx2 inhibitors in the treatment of OA and providing evidence from a genetic perspective.

BACKGROUND: Fatigue is a common symptom that negatively affects the outcomes and functions of rheumatoid arthritis (RA) patients. This study aimed to assess the fatigue by two scales and validate their consistency, also to comprehensively evaluate fatigue-related risk factors in RA patients.
METHODS: In this case-control study, the fatigue of 160 RA patients and 60 healthy controls was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and the Chinese version of the Brief Fatigue Inventory (BFI-C). The 28-joint disease activity score using erythrocyte sedimentation rate of RA patients was assessed.
RESULTS: The BRAF-MDQ and BFI-C scores were elevated in RA patients versus healthy controls (all p < .001). Interestingly, BRAF-MDQ global fatigue score positively correlated with BFI-C global fatigue score in both RA patients (r = .669, p < .001) and healthy controls (r = .527, p < .001); meanwhile, Kendall\'s tau-b test showed a high consistency between BRAF-MDQ and BFI-C global fatigue scores in RA patients (W = 0.759, p < .001) and healthy controls (W = 0.933, p < .001). Notably, higher education level (В = -4.547; 95% confidence interval: -7.065, -2.029; p < .001) and swollen joint count (В = 1.965; 95% confidence interval: 1.375, 2.554; p < .001) independently related to BRAF-MDQ global fatigue score; higher education level (В = -0.613; 95% confidence interval: -0.956, -0.269; p = .001) and clinical disease activity index (В = 0.053; 95% confidence interval: 0.005, 0.102; p = .032) independently linked with BFI-C global fatigue score.
CONCLUSIONS: Fatigue commonly occurs in RA patients, which independently relates to education level and disease activity. Furthermore, BRAF-MDQ and BFI-C scales exhibit a high consistency in assessing fatigue.

UNASSIGNED: The pain and sleep disorders caused by arthritis are health issues that have been re-emphasized with the aging population. However, the majority of research on arthritis and sleep disorders has focused on cases that have already been diagnosed with arthritis. This research aims to explore the correlation between sleep duration and new-onset arthritis in middle-aged and older adult individuals.
UNASSIGNED: Utilizing data from the China Health and Retirement Longitudinal Study from baseline (2011) to the Wave 3 follow-up (2018), we conducted a 7-year longitudinal investigation targeting populations with valid sleep questionnaire records and without arthritis. Sleep duration was assessed from nighttime sleep and daytime nap records. The new-onset of arthritis was determined based on self-reported diagnosis. We employed different logistic regression models to consider the potential impact of sleep duration on arthritis and conducted mediation analyses to assess the involvement of BMI in the association between sleep duration and the new-onset risk of arthritis.
UNASSIGNED: Out of the 6,597 individuals analyzed in the cohort, 586 (8.9%) were diagnosed with new-onset arthritis. Median sleep duration was notably shorter in the new-onset arthritis group (6.63 vs. 6.41 h, p < 0.05). There was a notable negative correlation found between new-onset risk of arthritis and sleep duration, with each Interquartile Range (IQR) increment in sleep leading to a 16% risk reduction (OR: 0.864; 95% CI: 0.784-0.954). Stratified analyses revealed BMI as a potential modifier in the sleep-arthritis relationship (P for interaction = 0.05). Mediation analyses further showed that about 3.5% of the association was mediated by BMI. Additionally, the inclusion of sleep duration improved the arthritis predictive power of our model, with an IDI of 0.105 (0.0203, 0.1898) and an NRI of 0.0013 (0.0004, 0.0022) after adding sleep duration to the basic model.
UNASSIGNED: In the middle-aged and older adult demographic of China, increased sleep duration is associated with a decreased new-onset risk of arthritis, with BMI potentially playing a role in mediating this connection.

As a crucial endogenous reactive oxygen species, hypochlorous acid (HClO) plays an indispensable role in numerous physiological and pathological processes. Additionally, it serves as a biomarker closely associated with inflammation and liver injury. The utilization of near-infrared fluorescence probes has surged in recent years for live biological imaging, owing to their minimal tissue damage and potent tissue penetration capabilities. In this work, a novel near-infrared fluorescence probe MB-HPD was synthesized to sensitively detect HClO. Probe MB-HPD exhibits remarkable selectivity, high sensitivity (14.3 nM), and rapid response towards HClO (20 s). Probe MB-HPD has demonstrated successful application in the imaging of HClO within cells and zebrafish. Remarkably, it has proven to be effective for detecting HClO within environmental samples, as well as imaging HClO in mice models of arthritis and APAP-induced liver injury. These findings indicate the broad applicability of probe MB-HPD, offering a promising avenue for designing highly selective near-infrared fluorescence probes suitable for real-time HClO monitoring.

BACKGROUND: Nickel is a common metallic element in orthopedic implanted devices and living environment exposures. It is associated with varieties of diseases. The purpose of this investigation was to explore the correlation between nickel exposure and the prevalence of arthritis.
METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2018. Multivariate logistic regression was utilized to analyze the relationship between urinary nickel levels and arthritis. In addition, hierarchical modeling further explored the interactions and trends between urinary nickel levels and arthritis. Propensity score matching (PSM) method was used to reduce the effect of confounders. Additionally, restricted cubic spline curve (RCS) was used to assess the possible nonlinear association between urinary nickel and arthritis.
RESULTS: The investigation was comprised of 139 arthritis patients and 547 healthy participants. After correction by PSM, there was a positive correlation between arthritis and Nickel exposure levels. The risk of developing arthritis was significantly increased when nickel exposure levels were in the Q4 interval (OR=2.25, 95 % CI=1.03-5.02). When stratified by age and sex, nickel exposure was significantly and positively associated with arthritis in the subgroup aged over 65 years. (OR=2.78,95 %CI=1.20-6.46). Also, the difference between nickel exposure and arthritis was significant in the different gender subgroups (interaction P<0.05). Restricted cubic spline (RCS) results showed a significant linear association between nickel exposure levels and arthritis. In addition, there was a non-linear association between nickel exposure and arthritis across gender and age subgroups.
CONCLUSIONS: A significant positive association between nickel exposure levels and arthritis was showed by the experimental data. Controlling the use of nickel-containing medical prostheses and reducing exposure to nickel-containing daily necessity could help to slow the onset of arthritis.

BACKGROUND: Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression.
METHODS: We conducted a two-sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome-wide association studies (GWASs) and the largest GWAS meta-analysis. MR analysis mainly used inverse-variance weighted method; supplementary methods included weighted median, weighted mode, and MR-Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy.
RESULTS: After adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01-1.02, p = 2.96 × E - 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04-1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10-1.42, p = 6.46 × E - 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19-1.94, p ≤ 8.94 × E - 4).
CONCLUSIONS: There is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.

Studies have indicated that the preservation of joint health and the facilitation of damage recovery are predominantly contingent upon the joint\'s microenvironment, including cell-cell interactions, the extracellular matrix\'s composition, and the existence of local growth factors. Mesenchymal stem cells (MSCs), which possess the capacity to self-renew and specialize in many directions, respond to cues from the microenvironment, and aid in the regeneration of bone and cartilage, are crucial to this process. Changes in the microenvironment (such as an increase in inflammatory mediators or the breakdown of the extracellular matrix) in the pathological context of arthritis might interfere with stem cell activation and reduce their ability to regenerate. This paper investigates the potential role of joint microenvironmental variables in promoting or inhibiting the development of arthritis by influencing stem cells\' ability to regenerate. The present status of research on stem cell activity in the joint microenvironment is also outlined, and potential directions for developing new treatments for arthritis that make use of these intervention techniques to boost stem cell regenerative potential through altering the intra-articular environment are also investigated. This review\'s objectives are to investigate these processes, offer fresh perspectives, and offer a solid scientific foundation for the creation of arthritic treatment plans in the future.

UNASSIGNED: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the body. Periploca forrestii was a miao ethnic drug in China that was used to treat arthritis for hundreds of years. But, the therapeutic mechanism is so far unknown. Therefore, the chemical component and effect of Periploca forrestii on arthritis in rats were studied using HPLC-QTOF MS, micro-CT, and other experiments in this paper.
UNASSIGNED: Male Sprague-Dawley rats were used to assess the in vivo activity. HPLC QTOF-MS was used to analyze the chemical profile of the P. forrestii (PF). Bovine type II collagen and Complete Freund\'s Adjuvant were used to stimulate and construct the collagen-induced arthritis (CIA) model. Three dosages of PF (100 mg/kg, 200 mg/kg, 400 mg/kg) were used to evaluate in vivo activity. Methotrexate was used as the positive drug. H/E staining and micro-CT methods were used to monitor the pathological changes of CIA rats. ELISA method was used to assess the serum level of immune- and inflammation-related cytokines. Immunohistochemical experiments were used to test the gene expression in JAK and Nf-κB pathways.
UNASSIGNED: 42 compounds were identified from PF. PF administration lowered the increased spleen index compared with that of control and MTX groups, and partially restored body weight, reduced paw swelling, and arthritis score compared with the model group. Macroscopic assessment indicated inflamed paw with significant swelling in the model group, while the extent of inflammation and swelling was attenuated by both MTX and PF. H/E staining experiments demonstrated that pathological changes of synovial cells and infiltration of inflammatory cells were observed in the model group. In contrast, the MTX and PF treatment partially reversed these pathological changes. Micro-CT examination showed severe injuries and scars caused by inflammation for the model group, and in the high-dosage group (400 mg/kg) the inflammation-caused injuries and scars were dramatically ameliorated. Mechanism study showed that PF restored Nf-κB phosphorylation and JAK2 expression compared with the model group.
UNASSIGNED: P. forrestii possesses a potent effect on CIA rats. Nf-κB and JAK2 pathways are involved in its protective effect on CIA.