Pathogenesis of gout: Exploring more therapeutic target.

Gout is a chronic metabolic and immune disease, and its specific pathogenesis is still unclear. When the serum uric acid exceeds its saturation in the blood or tissue fluid, it is converted to monosodium urate crystals, which lead to acute arthritis of varying degrees, urinary stones, or irreversible peripheral joint damage, and in severe cases, impairment of vital organ function. Gout flare is a clinically significant state of acute inflammation in gout. The current treatment is mostly anti-inflammatory analgesics, which have numerous side effects with limited treatment methods. Gout pathogenesis involves many aspects. Therefore, exploring gout pathogenesis from multiple perspectives is conducive to identifying more therapeutic targets and providing safer and more effective alternative treatment options for patients with gout flare. Thus, this article is of great significance for further exploring the pathogenesis of gout. The author summarizes the pathogenesis of gout from four aspects: signaling pathways, inflammatory factors, intestinal flora, and programmed cell death, focusing on exploring more new therapeutic targets.

Models of gouty nephropathy: exploring disease mechanisms and identifying potential therapeutic targets.

Gouty nephropathy (GN) is a metabolic disease with persistently elevated blood uric acid levels. The main manifestations of GN are crystalline kidney stones, chronic interstitial nephritis, and renal fibrosis. Understanding the mechanism of the occurrence and development of GN is crucial to the development of new drugs for prevention and treatment of GN. Currently, most studies exploring the pathogenesis of GN are primarily based on animal and cell models. Numerous studies have shown that inflammation, oxidative stress, and programmed cell death mediated by uric acid and sodium urate are involved in the pathogenesis of GN. In this article, we first review the mechanisms underlying the abnormal intrinsic immune activation and programmed cell death in GN and then describe the characteristics and methods used to develop animal and cell models of GN caused by elevated uric acid and deposited sodium urate crystals. Finally, we propose potential animal models for GN caused by abnormally high uric acid levels, thereby provide a reference for further investigating the methods and mechanisms of GN and developing better prevention and treatment strategies.

Regulatory Effects of Quercetin on Bone Homeostasis: Research Updates and Future Perspectives.

The imbalance of bone homeostasis has become a major public medical problem amid the background of an aging population, which is closely related to the occurrence of osteoporosis, osteoarthritis, and fractures. Presently, most drugs used in the clinical treatment of bone homeostasis imbalance are bisphosphonates, calcitonin, estrogen receptor modulators, and biological agents that inhibit bone resorption or parathyroid hormone analogs that promote bone formation. However, there are many adverse reactions. Therefore, it is necessary to explore potential drugs. Quercetin, as a flavonol compound with various biological activities, is widely distributed in plants. Studies have found that quercetin can regulate bone homeostasis through multiple pathways and targets. An in-depth exploration of the pharmacological mechanism of quercetin is of great significance for the development of new drugs. This review discusses the therapeutic mechanisms of quercetin on bone homeostasis, such as regulating the expression of long non-coding RNA, signaling pathways of bone metabolism, various types of programmed cell death, bone nutrients supply pathways, anti-oxidative stress, anti-inflammation, and activation of Sirtuins. We also summarize recent progress in improving quercetin bioavailability and propose some issues worth paying attention to, which may help guide future research efforts.

An integrative analysis to predict the active compounds and explore polypharmacological mechanisms of Orthosiphon stamineus Benth.

BACKGROUND: Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. METHODS: Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. RESULTS: A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. CONCLUSION: This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.

Potential Therapeutic Mechanism of Radix Angelicae Biseratae and Dipsaci Radix Herb Pair against Osteoarthritis: Based on Network Pharmacology and Molecular Docking.

Background: A major contributor to older disability is osteoarthritis. Radix Angelicae Biseratae (known as Duhuo in China, DH, the dried rhizome of Angelica pubescens) and Dipsaci Radix (known as Xuduan in China, XD, the dried rhizome of Dipsacus asper Wall) herb pair (DXHP) is widely used to treat osteoarthritis, but the underlying molecular mechanisms still have not been revealed. This research aimed to illustrate the therapeutic mechanism of DXHP against osteoarthritis through the techniques of network pharmacology and molecular docking. Methods: Gene targets for osteoarthritis and active ingredients for DXHP were screened based on the pharmacology public database and the gene-disease target database. The software program Cytoscape was used to visualize the active chemical target-disease gene network. The STRING biological information website was used to investigate protein interactions. On the Metascape bioinformatics website, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out. The molecular docking of the important chemicals and primary targets identified by the aforementioned screening was performed using Autodock software. Results: Twenty-six active substances from the DXHP that had strong connections to 138 osteoarthritis-related targets were screened out. According to network analysis, TNF, GAPDH, IL-6, AKT-1, IL-1B, and VEGFA are prospective therapeutic targets, while osthole, cauloside A, ammidin, angelicone, beta-sitosterol, and asperosaponin VI may be significant active components. 1705 biological processes (BP), 155 molecular functions (MF), and 89 cellular components (CC) were identified by GO analysis. KEGG analysis indicated that IL-17, NF-kappa B, HIF-1, MAPK, and AGE-RAGE signaling pathways are potentially involved. Molecular docking showed that cauloside A, osthole, and ß-sitosterol have excellent binding activity with main targets. Conclusions: This study comprehensively illuminated the active ingredients, potential targets, primary pharmacological effects, and relevant mechanisms of the DXHP in the treatment of OA. These findings provide fresh thoughts into the therapeutic mechanisms of the main active ingredients of DXHP and provide a reference for further exploration and clinical applications of DXHP.

Clinical efficacy of Yiqi Yangxue formula on knee osteoarthritis and unraveling therapeutic mechanism through plasma metabolites in rats.

Objective: To observe the clinical efficacy and safety of Yiqi Yangxue formula (YQYXF) on knee osteoarthritis (KOA), and to explore the underlying therapeutic mechanism of YQYXF through endogenous differential metabolites and their related metabolic pathways. Methods: A total of 61 KOA patients were recruited and divided into the treatment group (YQYXF, 30 cases) and the control group (celecoxib, Cxb, 31 cases). Effects of these two drugs on joint pain, swelling, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) were observed, and their safety and adverse reactions were investigated. In animal experiments, 63 SD rats were randomly divided into normal control (NC) group, sham operation (sham) group, model (KOA) group, Cxb group, as well as low-dose (YL), medium-dose (YM), and high-dose groups of YQYXF (YH). The KOA rat model was established using a modified Hulth method. Ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS)-based metabolomics technology was used to analyze the changes of metabolites in plasma samples of rats. Comprehensive (VIP) >1 and t-test p < 0.05 conditions were used to screen the disease biomarkers of KOA, and the underlying mechanisms of YQYXF were explored through metabolic pathway enrichment analysis. The related markers of YQYXF were further verified by ELISA (enzyme-linked immunosorbent assay). Results: YQYXF can improve joint pain, swelling, range of motion, joint function, Michel Lequesen index of severity for osteoarthritis (ISOA) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, ESR, and CRP. No apparent adverse reactions were reported. In addition, YQYXF can improve cartilage damage in KOA rats, reverse the abnormal changes of 16 different metabolites, and exert an anti-KOA effect mainly through five metabolic pathways. The levels of reactive oxygen species (ROS) and glutathione (GSH) were significantly decreased after the treatment of YQYXF. Conclusion: YQYXF can significantly improve the clinical symptoms of KOA patients without obvious adverse reactions. It mainly improved KOA through modulating lipid metabolism-related biomarkers, reducing lipid peroxidation and oxidative stress.

Polyphenols: Natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective.

As natural functional bioactive ingredients found in foods and plants, polyphenols play various antioxidant and anti-inflammatory roles to prevent the development of disease and restore human health. The multi-target modulation of polyphenols provides a novel practical therapeutic strategy for neurodegenerative diseases that are difficult to treat with traditional drugs like glutathione and cholinesterase inhibitors. This review mainly focuses on the efficacy of polyphenols on ischemic stroke, Parkinson's disease and Alzheimer's disease, including in vivo and in vitro experimental studies. It is further emphasized that polyphenols exert neuroprotective effects primarily through inhibiting production of oxidative stress and inflammatory cytokines, which may be the underlying mechanism. However, polyphenols are still rarely used as medicines to treat neurodegenerative diseases. Due to the lack of clinical trials, the mechanism of polyphenols is still in the stage of insufficient exploration. Future large-scale multi-center randomized controlled trials and in-depth mechanism studies are still needed to fully assess the safety, efficacy and side effects of polyphenols.

The compact Casπ (Cas12l) 'bracelet' provides a unique structural platform for DNA manipulation.

CRISPR-Cas modules serve as the adaptive nucleic acid immune systems for prokaryotes, and provide versatile tools for nucleic acid manipulation in various organisms. Here, we discovered a new miniature type V system, CRISPR-Casπ (Cas12l) (~860 aa), from the environmental metagenome. Complexed with a large guide RNA (~170 nt) comprising the tracrRNA and crRNA, Casπ (Cas12l) recognizes a unique 5' C-rich PAM for DNA cleavage under a broad range of biochemical conditions, and generates gene editing in mammalian cells. Cryo-EM study reveals a 'bracelet' architecture of Casπ effector encircling the DNA target at 3.4 Å resolution, substantially different from the canonical 'two-lobe' architectures of Cas12 and Cas9 nucleases. The large guide RNA serves as a 'two-arm' scaffold for effector assembly. Our study expands the knowledge of DNA targeting mechanisms by CRISPR effectors, and offers an efficient but compact platform for DNA manipulation.

Landscape Classification System Based on RKM Clustering for Soil Survey UAV Images-Case Study of the Small Hilly Areas in Jurong City.

With the advantages of high accuracy, low cost, and flexibility, Unmanned Aerial Vehicle (UAV) images are now widely used in the fields of land survey, crop monitoring, and soil property prediction. Since the distribution of soil and landscape are closely related, this study makes use of the advantages of UAV images to classify the landscape to build a landscape classification system for soil investigation. Firstly, land use, object, and topographic factor were selected as landscape factors based on soil-forming factors. Then, based on multispectral images and Digital Elevation Models (DEM) acquired by UAV, object-oriented classification of different landscape factors was carried out. Additionally, we selected 432 sample data and validation data from the field survey. Finally, the landscape factor classification results were superimposed to obtain the landscape unit applicable to the system classification. The landscape classification system oriented to the soil survey was constructed by clustering 11,897 landscape units through the rough K-mean clustering algorithm. Compared to K-mean clustering, the rough K-mean clustering was better, with a Silhouette Coefficient of 0.26247 significantly higher than that of K-mean clustering. From the classification results, it can be found that the overall classification results are somewhat fragmented, but the landscape boundaries at the small area scale are consistent with the actual situation and the fragmented small spots are less. Comparing the small number of landscape boundaries obtained from the actual survey, we can find that the landscape boundaries in the landscape classification map are generally consistent with the actual landscape boundaries. In addition, through the analysis of two soil profile data within a landscape category, we found that the identified soil type of soil formation conditions and the landscape factor type of the landscape category is approximately the same. Therefore, this landscape classification system can be effectively used for soil surveys, and this landscape classification system is important for soil surveys to carry out the selection of survey routes, the setting of profile points, and the determination of soil boundaries.

New insights into the interplay between autophagy and cartilage degeneration in osteoarthritis.

Autophagy is an intracellular degradation system that maintains the stable state of cell energy metabolism. Some recent findings have indicated that autophagy dysfunction is an important driving factor for the occurrence and development of osteoarthritis (OA). The decrease of autophagy leads to the accumulation of damaged organelles and macromolecules in chondrocytes, which affects the survival of chondrocytes and ultimately leads to OA. An appropriate level of autophagic activation may be a new method to prevent articular cartilage degeneration in OA. This minireview discussed the mechanism of autophagy and OA, key autophagy targets regulating OA progression, and evaluated therapeutic applications of drugs targeting autophagy in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.

Digital Mapping of Soil Organic Carbon Based on Machine Learning and Regression Kriging.

In the last two decades, machine learning (ML) methods have been widely used in digital soil mapping (DSM), but the regression kriging (RK) model which combines the advantages of the ML and kriging methods has rarely been used in DSM. In addition, due to the limitation of a single-model structure, many ML methods have poor prediction accuracy in undulating terrain areas. In this study, we collected the SOC content of 115 soil samples in a hilly farming area with continuous undulating terrain. According to the theory of soil-forming factors in pedogenesis, we selected 10 topographic indices, 7 vegetation indices, and 2 soil indices as environmental covariates, and according to the law of geographical similarity, we used ML and RK methods to mine the relationship between SOC and environmental covariates to predict the SOC content. Four ensemble models-random forest (RF), Cubist, stochastic gradient boosting (SGB), and Bayesian regularized neural networks (BRNNs)-were used to fit the trend of SOC content, and the simple kriging (SK) method was used to interpolate the residuals of the ensemble models, and then the SOC and residual were superimposed to obtain the RK prediction result. Moreover, the 115 samples were divided into calibration and validation sets at a ratio of 80%, and the tenfold cross-validation method was used to fit the optimal parameters of the model. From the results of four ensemble models: RF performed best in the calibration set (R2c = 0.834) but poorly in the validation set (R2v = 0.362); Cubist had good accuracy and stability in both the calibration and validation sets (R2c = 0.693 and R2v = 0.445); SGB performed poorly (R2c = 0.430 and R2v = 0.336); and BRNN had the lowest accuracy (R2c = 0.323 and R2v = 0.282). The results showed that the R2 of the four RK models in the validation set were 0.718, 0.674, 0.724, and 0.625, respectively. Compared with the ensemble models without superimposed residuals, the prediction accuracy was improved by 0.356, 0.229, 0.388, and 0.343, respectively. In conclusion, Cubist has high prediction accuracy and generalization ability in areas with complex topography, and the RK model can make full use of trends and spatial structural factors that are not easy to mine by ML models, which can effectively improve the prediction accuracy. This provides a reference for soil survey and digital mapping in complex terrain areas.

Radiomics combined with clinical features in distinguishing non-calcifying tuberculosis granuloma and lung adenocarcinoma in small pulmonary nodules.

Aim: To evaluate the performance of radiomics models with the combination of clinical features in distinguishing non-calcified tuberculosis granuloma (TBG) and lung adenocarcinoma (LAC) in small pulmonary nodules. Methodology: We conducted a retrospective analysis of 280 patients with pulmonary nodules confirmed by surgical biopsy from January 2017 to December 2020. Samples were divided into LAC group (n = 143) and TBG group (n = 137). We assigned them to a training dataset (n = 196) and a testing dataset (n = 84). Clinical features including gender, age, smoking, CT appearance (size, location, spiculated sign, lobulated shape, vessel convergence, and pleural indentation) were extracted and included in the radiomics models. 3D slicer and FAE software were used to delineate the Region of Interest (ROI) and extract clinical features. The performance of the model was evaluated by the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC). Results: Based on the model selection, clinical features gender, and age in the LAC group and TBG group showed a significant difference in both datasets (P < 0.05). CT appearance lobulated shape was also significantly different in the LAC group and TBG group (Training dataset, P = 0.034; Testing dataset, P = 0.030). AUC were 0.8344 (95% CI [0.7712-0.8872]) and 0.751 (95% CI [0.6382-0.8531]) in training and testing dataset, respectively. Conclusion: With the capacity to detect differences between TBG and LAC based on their clinical features, radiomics models with a combined of clinical features may function as the potential non-invasive tool for distinguishing TBG and LAC in small pulmonary nodules.

Jian Pi Shen Shi formula alleviates hyperuricemia and related renal fibrosis in uricase-deficient rats via suppression of the collagen-binding pathway.

AIM: Jian Pi Shen Shi Formula (JPSSF) is a beneficial treatment for hyperuricemia and related tissue damage in the clinical setting. This study was designed to investigate its therapeutic potential and underlying mechanisms in uricase-deficient rats (Uox-/- rats). METHODS: Uox-/- rats were used to assess the therapeutic potential of JPSSF on hyperuricemia. Protein extracts from renal tissues of a Uox-/- group and a JPSSF group were analyzed using tandem mass tag labeling quantitative proteomic workflow. Collagen deposition in Uox-/- rat kidneys was analyzed by Masson trichromatic staining. The gene expression associated with collagen-binding-related signaling pathways in the kidneys was further explored using quantitative polymerase chain reaction assay. The protein expressions of collagen 1a1 (col1a1), col6a1, and α-smooth muscle actin were measured by Western blotting and immunohistochemistry. RESULTS: JPSSF significantly decreased renal function indices and alleviated renal injuries. The action of JPSSF was manifested by down-regulation of col6a1 and interleukin-1 receptor-associated kinase-like 2, which blocked the binding sites on collagen and further prevented kidney injury. The anti-renal fibrosis effect of JPSSF was confirmed by reducing the collagen deposition and hydroxyproline concentrations. JPSSF treatment also intensely down-regulated the mRNA and protein expressions of col6a1, col1a1, and α-smooth muscle actin, which inhibited the function of the collagen-binding-related signaling pathway. CONCLUSION: Our results indicated that JPSSF notably ameliorated hyperuricemia and related renal fibrosis in Uox-/- rats through lowering uric acid and down-regulating the function of the collagen-binding pathway. This suggested that JPSSF is a potential empirical formula for treating hyperuricemia and accompanying renal fibrosis.

Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. Microbial infection is considered a crucial inducer of RA. Alterations in the composition of intestinal bacteria in individuals with preclinical and established RA suggest a vital role of the gut microbiota in immune dysfunction characteristic of RA. However, the mechanisms by which gut dysbiosis contributes to RA are not fully understood. Furthermore, multiple therapies commonly used to treat RA may alter gut microbiota diversity, suggesting that modulating the gut microbiota may help prevent or treat RA. Hence, a better understanding of the changes in the gut microbiota that accompany RA should aid the development of novel therapeutic approaches. This mini-review discusses the impact of gut dysbiosis in the pathogenesis of RA, the selection of gut microbiota-related biomarkers for diagnosing RA, and provides examples of cross-modulation between the gut microbiota and some drugs commonly used to treat RA. Some suggestions and outlooks are also raised, which may help guide future research efforts.

Third dose of anti-SARS-CoV-2 inactivated vaccine for patients with RA: Focusing on immunogenicity and effects of RA drugs.

Objectives: To evaluate the immunogenicity of the third dose of inactivated SARS-CoV-2 vaccine in rheumatoid arthritis (RA) patients and explore the effect of RA drugs on vaccine immunogenicity. Methods: We recruited RA patients (n = 222) and healthy controls (HC, n = 177) who had been injected with a third dose of inactivated SARS-CoV-2 vaccine, and their neutralizing antibody (NAb) titer levels were assessed. Results: RA patients and HC were age- and gender-matched, and the mean interval between 3rd vaccination and sampling was comparable. The NAb titers were significantly lower in RA patients after the third immunization compared with HC. The positive rate of NAb in HC group was 90.4%, while that in RA patients was 80.18%, and the difference was significant. Furthermore, comparison of NAb titers between RA treatment subgroups and HC showed that the patients in the conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) group exhibited no significant change in NAb titers, while in those receiving the treatment of biological DMARDs (bDMARDs), Janus Kinase (JAK) inhibitors, and prednisone, the NAb titers were significantly lower. Spearman correlation analysis revealed that NAb responses to SARS-CoV-2 in HC did differ significantly according to the interval between 3rd vaccination and sampling, but this finding was not observed in RA patients. In addition, NAb titers were not significantly correlated with RA-related laboratory indicators, including RF-IgA, RF-IgG, RF-IgM, anti-CCP antibody; C-RP; ESR; NEUT% and LYMPH%. Conclusion: Serum antibody responses to the third dose of vaccine in RA patients were weaker than HC. Our study will help to evaluate the efficacy and safety of booster vaccination in RA patients and provide further guidance for adjusting vaccination strategies.

Aberrant messenger RNA expression in peripheral blood mononuclear cells is associated with gouty arthritis.

AIM: Gouty arthritis (GA) is a type of self-limiting inflammatory arthritis caused by deposition of monosodium urate (MSU). This study aimed to analyze the expression variation of messenger RNAs (mRNAs) in GA patients and investigated the role of mRNAs in GA pathogenesis. METHODS: Five patients with acute GA (AGA), 5 with non-acute GA (NAGA), and 5 healthy controls (HC) were recruited to examine differential mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) and explore whether mRNA is involved in the pathogenesis of AGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to study the biological functions of differentially expressed mRNA and the relationship between genes and signal pathways. RESULTS: Compared with HC, the AGA group had 1456 differentially expressed mRNAs, while the NAGA group had 437 differentially expressed mRNAs and compared with the NAGA group, 115 differentially expressed mRNAs were found in the AGA group. GO analysis showed that the differentially expressed mRNA in the AGA group was mainly enriched in processes related to leukocyte activation and immune response, while KEGG analysis showed that "Staphylococcus aureus infection" and "Cytokine-cytokine receptor interaction" are enriched in the up-regulated mRNAs in the AGA group. CONCLUSION: This study identified genes and pathways that are differentially expressed during the onset of AGA, which might reveal part of the pathogenesis of the disease and provide clues to explaining the severe pain associated with disease onset and the rapid development of inflammatory response that subsides by itself.

How to Model Rheumatoid Arthritis in Animals: From Rodents to Non-Human Primates.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. At present, rodent models are primarily used to study the pathogenesis and treatment of RA. However, the genetic divergences between rodents and humans determine differences in the development of RA, which makes it necessary to explore the establishment of new models. Compared to rodents, non-human primates (NHPs) are much more closely related to humans in terms of the immune system, metabolic conditions, and genetic make-up. NHPs model provides a powerful tool to study the development of RA and potential complications, as well as preclinical studies in drug development. This review provides a brief overview of the RA animal models, emphasizes the replication methods, pros and cons, as well as evaluates the validity of the rodent and NHPs models.

Immunogenicity of Inactivated SARS-CoV-2 Vaccines in Patients With Rheumatoid Arthritis: A Case Series.

Objectives: Attenuated humoral response to mRNA SARS-CoV-2 vaccines has been reported in some patients with autoimmune disease, e.g., rheumatoid arthritis (RA). However, data of immune responses to inactivated SARS-CoV-2 vaccine in the RA population are still unknown. Herein, the safety and immunogenicity of inactivated SARS-CoV-2 vaccines in RA patients were analyzed. Methods: Seventy five RA patients and 26 healthy controls (HC) were respectively recruited from Yunnan Provincial Hospital of Traditional Chinese Medicine and the community in Kunming city. Neutralizing Antibody (NAb) Test ELISA kit was used to measure the percentage of inhibition. AKA (anti-keratin antibody) positivity was detected using indirect immunofluorescence. Rheumatoid factor (RF)-IgA was detected by ELISA. RF-IgG, RF-IgM, and anti-cyclic citrullinated peptide (CCP) antibodies were measured by chemiluminescence. ESR (erythrocyte sedimentation rate) was detected by ESR analyzer. C-RP (c-reactive protein) was detected by immunoturbidimetry. NEUT% (percentage of neutrophils) and LYMPH% (percentage of percentage) were calculated by a calculation method. Results: Compared with the HC group, the percentage of inhibition was significantly lower in RA patients receiving two doses of vaccines. Vaccines-induced percentage of inhibition was the lowest in RA patients who had not been vaccinated. In total 80.77% of the HC group had a percentage of inhibition ≧20%, compared with 45.24% of vaccinated RA patients and 6.06% of unvaccinated RA patients. Spearman correlation analysis revealed that antibody responses to SARS-CoV-2 did not differ between RA patients according to their age and disease duration. Furthermore, the results showed that no correlation was found between the percentage of inhibition and indices for RA, including RF-IgA, IgG, IgM; anti-CCP antibody; ESR; C-RP; NEUT% and LYMPH%. Conclusion: Our study showed inactivated vaccine-induced SARS-COV-2 antibody responses differ in RA patients and healthy subjects, emphasizing the importance of a third or fourth vaccination in RA patients.

Ferroptosis in Rheumatoid Arthritis: A Potential Therapeutic Strategy.

Ferroptosis is one of the newly discovered forms of cell-regulated death characterized by iron-dependent lipid peroxidation. Extensive research has focused on the roles of ferroptosis in tumors, blood diseases, and neurological diseases. Some recent findings have indicated that ferroptosis may also be related to the occurrence and development of inflammatory arthritis. Ferroptosis may be a potential therapeutic target, and few studies in vitro and animal models have shown implications in the pathogenesis of inflammatory arthritis. This mini review discussed the common features between ferroptosis and the pathogenesis of rheumatoid arthritis (RA), and evaluated therapeutic applications of ferroptosis regulators in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.