Lixia Yuan

Context: Danggui Niantong granules (DGNTG), a traditional Chinese medicine, serve as an effective therapeutic agent for the treatment of rheumatoid arthritis (RA). However, the comprehensive molecular mechanisms of DGNTG in RA remain unclear. Increasing evidence highlights the significant role of competing endogenous RNAs (ceRNA) in diagnosing and treating various diseases. Objective: The study aims to explore the molecular mechanism of DGNTG in the treatment of RA through the ceRNA network. Materials and methods: The MH7A cells were divided into control group and DGNTG group (2 and 4 mg/mL).The proliferation, migration and invasion ability of MH7A were accessed using MTT assay, cloning formation, wound-healing assay transwell assay and Western blotting. Subsequently, ceRNA microarray analyses were performed and a circRNA-miRNA-mRNA ternary transcription network was established. The data were validated through qPCR. Results: DGNTG inhibited proliferation, suppressed migration and invasion in MH7A ( P < 0.05, 0.01 or  0.001 ), with the most pronounced effects observed in the DGNTG (4 mg/mL) group. Subsequently, we identified 301 differentially expressed mRNAs and 507 differentially expressed circRNAs (FC ≤ 0.5 or ≥2, P < 0.05 ). Bioinformatics analyses indicated that DGNTG may exert therapeutic effects through multiple pathways. Furthermore, we constructed a circRNA-miRNA-mRNA network and conducted additional bioinformatics analysis on this network. In addition, we developed a representative ceRNA network and analyzed the correlations among its components. Discussion and conclusions: This study presents evidence that DGNTG exerts anti-RA effects through the inhibition of synoviocyte proliferation, migration and invasion. Additionally, It provided a valuable resource for elucidating the mechanism of action of DGNTG by constructing a competing endogenous RNA network based on transcriptomic data obtained from DGNTG-treated MH7A cells.

Background: Osteoarthritis (OA) is a joint disorder that is characterized, among other features, by abnormal subchondral bone remodeling. Moxibustion, a traditional Chinese medicine treatment, has a long history in the clinical treatment of osteoarthritis and has demonstrated significant efficacy. However, the impact mechanisms of moxibustion on subchondral bone in osteoarthritis have yet to be elucidated. Purpose: This study investigated the specific effects and mechanisms of moxibustion on abnormal subchondral bone remodeling in OA. Methods: Anterior cruciate ligament transection (ACLT) surgery was performed on mice to establish an OA model, and moxibustion intervention for 4 weeks. The effects of moxibustion on knee osteoarthritis symptoms and walking ability were assessed by knee joint diameter measurement, von Frey test and footprint analysis. Micro-CT, TEM, immunofluorescence staining, and western blot were used to detect the contact between autophagy–lysosomal pathway and NLRP3 inflammasome in subchondral bone remodeling. Subsequently, proteomic analysis was performed on mouse subchondral bone. Results: We first discovered that moxibustion intervention effectively reduced inflammation in the subchondral bone, thereby balancing the activities of osteoblasts and osteoclasts. Moxibustion, with its warming and medicinal properties, significantly alleviated pain and swelling and enhanced walking ability in OA mice. The findings also suggested that moxibustion counteracted subchondral bone imbalance by inhibiting the activation of the NLRP3 inflammasome through increased autolysosome levels. Proteomic analysis and experimental validation revealed that moxibustion promoted ACSL1 expression to regulate autophagy in OA subchondral bone. Conclusion: Our study elucidated the molecular mechanism by which moxibustion improved the inflammatory environment and abnormal subchondral bone remodeling in OA mice by activating ACSL1-mediated autophagy, providing the basis and new insights for advancing moxibustion therapy in OA.

To investigate the causal relationship between rheumatoid arthritis (RA) and interstitial lung disease (ILD) in the East Asian population, we utilized Mendelian randomization (MR). Publicly available summarized data from genome-wide association studies on RA (4199 cases and 208,254 controls), and the data on ILD (1046 cases and 176,974 controls) were obtained from BioBank Japan. Eligible single nucleotide polymorphisms from East Asian populations were obtained from genome-wide association studies as instrumental variables, and 11 RA-related single nucleotide polymorphisms (P < 5 × 10⁻⁸) were selected as instrumental variables. MR analysis was performed using inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO with RA as the exposure data and ILD as the outcome data. Reliability was evaluated using Cochran Q test, MR-Egger intercept, leave-one-out analysis, and funnel plot. Inverse variance weighted results showed an odds ratio (95% confidence interval) of 1.29 (1.18–1.41), P = 3.99 × 10⁻⁸, indicating a positive association between RA and ILD. The reliability evaluation could adopt the fixed-effect model, and the absolute value of the MR-Egger regression intercept was 0.021, P > 0.05, and P value of Global Test in MR-PRESSO was 0.573. The test results of the leave-one-out showed that the results are robust, and the funnel plot indicated that the instrumental variables were not affected by potential factors. In conclusion, this study demonstrates that RA is a risk factor for ILD in the East Asian population.

This study aimed to examine whether dried fruit intake is causally associated with Osteoarthritis (OA). A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median (WM), and MR-Egger regression methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) meta-analyses for dried fruit intake in individuals included in the UK Biobank (n = 421,764; MRC-IEU consortium) as the exposure and a GWAS publicly available in PubMed for OA (total n = 484,598; case = 39,515, control = 445,083) as the outcome. We selected 41 single nucleotide polymorphisms at genome-wide significance from GWASs on dried fruit intake as the instrumental variables. The IVW method showed evidence to support a causal association between dried fruit intake and OA (beta = −0.020, SE = 0.009, P = .039). MR-Egger regression indicated no directional pleiotropy (intercept = 1E-05; P = .984), but it showed no causal association between dried fruit intake and OA (beta = −0.020, SE = 0.043, P = .610). However, the WM approach yielded evidence of a causal association between dried fruit intake and OA (beta = −0.026, SE = 0.012, P = .026). Cochran’s Q test showed the existence of heterogeneity, but the statistics of I ² showed low heterogeneity. The results of MR analysis support that dried fruit intake may be causally associated with a decreased risk of OA.

Danggui Niantong Granules (DGNTG) are a valid and reliable traditional herbal formula, commonly used in clinical practice to treat rheumatoid arthritis (RA). However, the mechanism of its effect on...

This study aimed to investigate the potential roles of circRNAs in regulating osteoarthritis (OA)-related ghrelin synthesis, autophagy induction, and the relevant molecular mechanisms. Results showed that Col2a1, Acan, ghrelin, and autophagy-related markers expression were downregulated, while matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) expressions increased in both IL-1β-induced rat chondrocytes and cartilage tissues of OA rats. A total of 130 circRNAs and 731 mRNAs were differentially expressed in IL-1β-induced rat chondrocytes. Among them, we found that circPan3 expression was significantly decreased in both cellular and animal OA models. CircPan3 directly targeted miR-667-5p. CircPan3 overexpression promoted Col2a1, Acan, ghrelin, beclin 1, and LC3-II expression but reduced MMP13 and ADAMTS5 expression in rat chondrocytes, whereas overexpression of miR-667-5p exhibited opposite effects on the above markers. Furthermore, we found that miR-667-5p bound directly to the 3′-UTR sequence of ghrelin gene. Moreover, the circPan3-induced alterations in chondrocytes were antagonized by miR-667-5p overexpression. Taken together, our findings demonstrate that circPan3 promotes ghrelin synthesis and chondrocyte autophagy via targeting miR-667-5p, protecting against OA injury. This study provided experimental evidence that circPan3/miR-667-5p/ghrelin axis might serve as targets of drug development for the treatment of OA.