Chemical screening links disulfiram with cardiac protection after ischemic injury.

Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction, however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited. Here, we report the identification and characterization of the FDA-approved drug disulfiram (DSF) as a cardioprotective compound. By applying high-throughput chemical screening, we found that DSF decreased H2O2-induced cardiomyocyte death by inhibiting Gasdermin D, but not ALDH1, in cardiomyocytes. Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia-reperfusion injury in rats. Therefore, this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease.

Identification and validation of oxeiptosis-associated lncRNAs and prognosis-related signature genes to predict the immune status in uterine corpus endometrial carcinoma.

As a novel cell death modality, oxeiptosis is mainly caused by oxidative stress. However, the associations of uterine corpus endometrial carcinoma (UCEC) with oxeiptosis-associated long non-coding RNAs (lncRNAs) are unknown. Here, to identify hub oxeiptosis-associated lncRNAs in UCEC, we collected the data for lncRNAs and gene expression in UCEC from The Cancer Genome Atlas (TCGA) database. Then, a lncRNA risk signature was constructed, and its prognostic value was further evaluated. Finally, the expression levels of hub lncRNA HOXB-AS3 were validated by quantitative RT-PCR analysis. MTT and wounding analyses were also applied to confirm the role of HOXB-AS3 knockdown on UCEC cells. Five lncRNAs associated with oxeiptosis and connected to the prognosis of UCEC were identified, and a risk signature was constructed based on these identified lncRNAs. Our clinical value analyses suggested that the risk signature was closely connected to the overall survival, TNM stage, and grade of UCEC patients. Meanwhile, compared to the conventional clinicopathological characteristics, this risk signature exhibited significantly higher diagnostic accuracy. Moreover, the potential mechanism analysis indicated a close connection of this risk signature to tumor stemness, m6A-related genes, immune cell infiltration, and immune subtypes. Based on the risk scores, we constructed a nomogram. In vitro experiments found that HOXB-AS3 was significantly higher expressed in UCEC cells, and the silence of HOXB-AS3 inhibited the proliferation and migration of UCEC cells. In conclusion, using five hub lncRNAs associated with oxeiptosis, we generated a risk signature, which could be applied in the novel therapeutic strategies of UCEC development.

P-type nitrogen-doped ß-Ga2O3: the role of stable shallow acceptor NO-VGa complexes.

In-depth understanding of the acceptor states and origins of p-type conductivity is essential and critical to overcome the great challenge for the p-type doping of ultrawide-bandgap oxide semiconductors. In this study we find that stable NO-VGa complexes can be formed with ε(0/-) transition levels significantly smaller than those of the isolated NO and VGa defects using N2 as the dopant source. Due to the defect-induced crystal-field splitting of the p orbitals of Ga, O and N atoms, and the Coulomb binding between NO(II) and VGa(I), an a' doublet state at 1.43 eV and an a'' singlet state at 0.22 eV above the valence band maximum (VBM) are formed for the ß-Ga2O3:NO(II)-VGa(I) complexes with an activated hole concentration of 8.5 × 1017 cm-3 at the VBM, indicating the formation of a shallow acceptor level and the feasibility to obtain p-type conductivity in ß-Ga2O3 even when using N2 as the dopant source. Considering the transition from NO(II)-V0Ga(I) + e to NO(II)-V-Ga(I), an emission peak at 385 nm with a Franck-Condon shift of 1.08 eV is predicted. These findings are of general scientific significance as well as technological application significance for p-type doping of ultrawide-bandgap oxide semiconductors.

Identification and validation of anoikis-associated gene SNCG as a prognostic biomarker in gastric cancer.

As a type of cell apoptosis, anoikis is caused by cells detachment from the extracellular matrix and anoikis resistance is central to cancer metastasis. Here, SNCG was identified as hub anoikis-associated gene in GC and associated with prognosis of patients with GC. To screen the hub anoikis-associated genes connected to GC, the database of Cancer Genome Atlas (TCGA) was employed. For further validating these identified genes, the Gene Expression Omnibus (GEO) dataset was applied, and Western blotting and quantitative Real-Time PCR were carried out. To Identify hub genes, we conducted the analyses of univariate Cox regression, differential expression, and weighted gene co-expression network analysis (WGCNA). According to the identified hub genes, we constructed a model of prognosis. Following complex analysis, SNCG was finally identified as hub anoikis-associated gene in GC. Indeed, K-M and receiver operating characteristic analyses suggested that the expression patterns of SNCG can be used as prognostic factors for GC survival. The expression and survival trends of SNCG were verified in the validation cohort and in vitro experimental analyses. The analysis of immune cell infiltration showed that the infiltrated immune cells varied among patients with GC and gene SNCG. Furthermore, due to the significant association of the constructed risk signature with patient age and survival, this risk signature can be used to predict the prognosis of GC. We suggest that SNCG was served as hub anoikis-associated gene in GC. Meanwhile, SNCG may have prognostic potential for overall patient survival.

Cuproptosis-associated genes and immune microenvironment characterization in breast cancer.

Excess Cu can cause cell death as a cofactor for essential enzymes. The relationship between cuproptosis-associated genes (CAGs) and breast cancer (BR) is not completely investigated. Here, the transcriptome expression and mutation profile data of BR samples from the Cancer Genome Atlas database were retrieved to identify CAGs. Patients with BR were clustered using consensus clustering. A least absolute shrinkage and selection operator analysis was then performed to construct a CAGs risk signature. As a result, all 13 cuproptosis regulators were significantly differentially expressed between BR and normal samples; among them, 9 cuproptosis genes were correlated with prognoses. Patients with BR were separated into 2 clusters that were associated with patient survival, clinical phenotypes, and immune infiltration, Based on the components of cuproptosis. Subsequently, genes differentially expressed between clusters were obtained, and 11 CAGs were ultimately incorporated into the risk signature. Functional analyses revealed that the risk signature correlated with patient outcomes, ER, PR, HER2 expression, and BR IHC subtypes. Additionally, immune microenvironment analyses showed that CAGs-high-risk patients exhibited lower immune cell infiltration and immune functions. Furthermore, high-risk BR patients had higher TMB, lower immune checkpoint expression, higher m6A gene expression, and higher tumor stemness. Finally, the immunophenoscore analysis revealed that the risk signature could potentially predict the immune response in BR and help guide the application of various immunotherapeutic drugs. Overall, the newly constructed CAGs risk signature presented a predictive value for the prognosis and tumor microenvironment of BR patients and can be further used in the guidance of immunotherapy for BR.

Identification of a predictive gene signature related to pyroptosis for the prognosis of cutaneous melanoma.

Pyroptosis is a form of inflammatory programmed cell death. However, because of no specific molecular biomarker, pyroptosis has not been considered as a novel therapeutic method to treat cutaneous melanoma (CM). Here, we identified pyroptosis genes that associate with the prognosis of CM patients and constructed an effective model for the prognostic prediction of CM patients. To identify genes related to pyroptosis that are differentially expressed in CM, we obtained gene expression data of CM patients and normal skin tissues from the Cancer Genome Atlas and the Genotype-Tissue Expression databases, and used another cohort obtained from Gene Expression Omnibus database for validation. Three genes (BST2, GBP5, and AIM2) that were associated with prognosis were found and incorporated into our prognostic model. Furthermore, we divided the patients into 2 groups: a high-risk group and a low-risk group. Functional analyses indicated that our model was correlated with patient survival and cancer growth. Multivariate and univariate Cox regressions revealed that the constructed model could serve as an independent prognostic factor for CM patients. Meanwhile, compared with other clinical characteristics, our model significantly improved the diagnostic accuracy. Gene function analysis revealed that pyroptosis genes BST2, GBP5, and AIM2 were differentially expressed in CM patients and positively associated with patient prognosis. Finally, a risk score was used to generate nomograms that displayed favorable discriminatory abilities for CM. In summary, our model could significantly predict the prognosis of CM patients and be used for the development of CM therapy.

Identification of m7G-associated lncRNA prognostic signature for predicting the immune status in cutaneous melanoma.

RNA modifications, including RNA methylation, are widely existed in cutaneous melanoma (CM). Among epigenetic modifications, N7-methylguanosine (m7G) is a kind of modification at 5' cap of RNA which participate in maintaining the stability of mRNA and various cell biological processes. However, there is still no study concerning the relationship between CM and m7G methylation complexes, METTL1 and WDR4. Here, long non-coding RNA (lncRNAs) and gene expression data of CM from the Cancer Genome Atlas (TCGA) database were retrieved to identify differentially expressed m7G-related lncRNAs connected with overall survival of CM. Then, Cox regression analyses was applied to construct a lncRNA risk signature, the prognostic value of identified signature was further evaluated. As a result, 6 m7G-associated lncRNAs that were significantly related to CM prognosis were incorporated into our prognostic signature. The functional analyses indicated that the prognostic model was correlated with patient survival, cancer metastasis, and growth. Meanwhile, its diagnostic accuracy was better than conventional clinicopathological characteristics. The pathway enrichment analysis showed that the risk model was enriched in several immunity-associated pathways. Moreover, the signature model was significantly connected with the immune subtypes, infiltration of immune cells, immune microenvironment, as well as several m6A-related genes and tumor stem cells. Finally, a nomogram based on the calculated risk score was established. Overall, a risk signature based on 6 m7G-associated lncRNAs was generated which presented predictive value for the prognosis of CM patients and can be further used in the development of novel therapeutic strategies for CM.

Lateralized differences for verbal learning across trials in temporal lobe epilepsy are not affected by surgical intervention.

This research aimed to broaden understanding of learning verbal material in participants with left- and right-sided mesial temporal lobe epilepsy (MTLE). We modeled word list-learning to determine how anterior temporal lobe resection affects verbal learning. Verbal learning (across trials) was assessed using the first five trials of the Rey Auditory Verbal Learning Test (RAVLT) in 128 participants with MTLE. Mixedeffects modeling was used to determine whether learning curves differed between participants with left- and right-sided MTLE pre- and post- anterior temporal lobe resection. Laterality of MTLE had a significant effect on both the model intercept and the linear slope, whereby participants with left-sided MTLE retained fewer words on both the first trial and on each subsequent trial than participants with right-sided MTLE; and this held regardless of anterior temporal lobe resection status (t(117) = -3.516, p < .001; t(120.50) = -2.049, p = .042, for intercept and linear slope, respectively). There were no significant differences in the learning curves after anterior temporal lobe resection surgery in either left- or right-sided MTLE. Our findings suggest that acquisition of verbal information may be especially impaired in patients with left-sided MTLE. Further, we show that verbal learning across trials was not affected by surgical intervention. This finding contributes to the broader understanding of the impacts of anterior temporal lobe resection on verbal memory function, and has important implications for the clinical management and surgical planning for patients with temporal lobe epilepsy.

Identifying the hub genes and immune infiltration related to pyroptosis in rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is one of the most common autoimmune joint disorders globally, but its pathophysiological mechanisms have not been thoroughly investigated. Pyroptosis significantly correlates with programmed cell death. However, targeting pyroptosis has not been considered as a therapeutic strategy in RA due to a lack of systematic studies on validated biomarkers. The present study aimed to identify hub pyroptosis biomarkers and immune infiltration in RA. The gene expression profiles of synovial tissues were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed pyroptosis genes (DEPGs). Meanwhile, the CIBERSORT algorithm was used to explore the association between immune infiltration and RA. Consequently, two hub DEPGs (EGFR and JUN) were identified as critical genes in RA. Through gene ontology and pathway enrichment analysis. EGFR and JUN were found to be primarily involved in the ErbB signaling pathway, PD-1 checkpoint pathway, GnRH signaling pathway, etc. Furthermore, for immune infiltration analysis, the pyroptosis genes EGFR and JUN were closely connected with four and one immune cell types, respectively. Overall, this study presents a novel method to identify hub DEPGs and their correlation with immune infiltration, which may provide novel perspectives into the diagnosis and treatment of patients with RA.

A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear. METHODS: Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database. RESULTS: Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.

Identifying hub genes and immune infiltration of osteoarthritis using comprehensive bioinformatics analysis.

BACKGROUND: Osteoarthritis (OA) is the most common chronic degenerative joint disorder globally that is characterized by synovitis, cartilage degeneration, joint space stenosis, and sub-cartilage bone hyperplasia. However, the pathophysiologic mechanisms of OA have not been thoroughly investigated. METHODS: In this study, we conducted various bioinformatics analyses to identify hub biomarkers and immune infiltration in OA. The gene expression profiles of synovial tissues from 29 healthy controls and 36 OA samples were obtained from the gene expression omnibus database to identify differentially expressed genes (DEGs). The CIBERSORT algorithm was used to explore the association between immune infiltration and arthritis. RESULTS: Eighteen hub DEGs were identified as critical biomarkers for OA. Through gene ontology and pathway enrichment analyses, it was found that these DEGs were primarily involved in PI3K-Akt signaling pathway and Rap1 signaling pathway. Furthermore, immune infiltration analysis revealed differences in immune infiltration between patients with OA and healthy controls. The hub gene ZNF160 was closely related to immune cells, especially mast cell activation in OA. CONCLUSION: Overall, this study presented a novel method to identify hub DEGs and their correlation with immune infiltration, which may provide novel insights into the diagnosis and treatment of patients with OA.

Activation of autophagy contributes to the protective effects of lycopene against oxidative stress-induced apoptosis in rat chondrocytes.

Oxidative stress is commonly associated with osteoarthritis (OA). Lycopene (LYC), a natural carotenoid compound, is an effective antioxidant with potential cartilage-protecting actions. However, how it affects hydrogen peroxide (H2 O2 )-induced damage to the cartilage is unclear. In this study, an in vitro oxidative stress model was developed via treating primary chondrocytes with H2 O2 . Western blot, immunohistochemistry, and quantitative RT-PCR (qRT-PCR) were used to assess the levels of related factors. Reactive oxygen species (ROS) and apoptosis levels were analyzed by the use of appropriate probes and flow cytometry. The expression and activity of stress-specific enzymes (malondialdehyde, superoxide dismutase, and catalase) were also assessed. The role of autophagy was explored by using the inhibitor, 3-methyladenine (3-MA), as well as monodansylcadaverine staining, western blotting, and red fluorescent protein-green fluorescent protein-light chain 3 lentivirus infection. The result showed LYC exerted significant chondrocyte-protective effects, including reduced inflammation and chondrocyte degradation, increased chondrocyte proliferation, apoptosis inhibition, and reduced ROS production. LYC could effectively induce autophagy in the H2 O2 treatment group, and this effect could be attenuated by 3-MA. In terms of mechanism, LYC played a role in inhibiting MAPK and PI3K/Akt/NF-κB axis, which down-regulates levels of mTOR and had a potential therapeutic significance for cartilage degeneration.

GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats.

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.

Identification and prognostic value of a glycolysis-related gene signature in patients with bladder cancer.

ABSTRACT: Bladder cancer (BC) is one of the most common malignancies worldwide. Several biomarkers related to the prognosis of patients with BC have previously been identified. However, these prognostic models use only one gene and are thus not reliable or accurate enough. The purpose of our study was to develop an innovative gene signature that has greater prognostic value in BC. So, in this study, we performed mRNA expression profiling of glycolysis-related genes in BC (n = 407) cohorts by mining data from The Cancer Genome Atlas (TCGA) database. The glycolysis-related gene sets were confirmed using the Gene Set Enrichment Analysis (GSEA). Using Cox regression analysis, a risk score staging model was built based on the genes that were determined to be significantly associated with BC outcome. Eventually, the system of risk score was structured to predict a patient's survival, and we identified four genes (CHPF, AK3, GALK1, and NUP188) that were associated with the outcomes of BC patients. According to the above-mentioned gene signature, patients were divided into two risk subgroups. The analysis showed that our constructed risk model was independent of clinical features and that the risk score was a highly powerful tool for predicting the overall survival (OS) of BC patients. Taking together, we identified a gene signature associated with glycolysis that could effectively predict the prognosis of BC patients. Our findings offer a new perspective for the clinical research and treatment of BC.

Integrated analysis identifies oxidative stress genes associated with progression and prognosis in gastric cancer.

Oxidative stress (OS) reactions are reported to be associated with oncogenesis and tumor progression. However, little is known about the potential diagnostic value of OS in gastric cancer (GC). This study identified hub OS genes associated with the prognosis and progression of GC and illustrated the underlying mechanisms. The transcriptome data and corresponding GC clinical information were collected from The Cancer Genome Atlas (TCGA) database. Aberrantly expressed OS genes between tumors and adjacent normal tissues were screened, and 11 prognosis-associated genes were identified with a series of bioinformatic analyses and used to construct a prognostic model. These genes were validated in the Gene Expression Omnibus (GEO) database. Furthermore, weighted gene co-expression network analysis (WGCNA) was subsequently conducted to identify the most significant hub genes for the prediction of GC progression. Analysis revealed that a good prognostic model was constructed with a better diagnostic accuracy than other clinicopathological characteristics in both TCGA and GEO cohorts. The model was also significantly associated with the overall survival of patients with GC. Meanwhile, a nomogram based on the risk score was established, which displayed a favorable discriminating ability for GC. In the WGCNA analysis, 13 progression-associated hub OS genes were identified that were also significantly associated with the progression of GC. Furthermore, functional and gene ontology (GO) analyses were performed to reveal potential pathways enriched with these genes. These results provide novel insights into the potential applications of OS-associated genes in patients with GC.

DNA methylation patterns-based subtype distinction and identification of soft tissue sarcoma prognosis.

ABSTRACT: Soft tissue sarcomas (STSs) are heterogeneous at the clinical with a variable tendency of aggressive behavior. In this study, we constructed a specific DNA methylation-based classification to identify the distinct prognosis-subtypes of STSs based on the DNA methylation spectrum from the TCGA database. Eventually, samples were clustered into 4 subgroups, and their survival curves were distinct from each other. Meanwhile, the samples in each subgroup reflected differentially in several clinical features. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was also conducted on the genes of the corresponding promoter regions of the above-described specific methylation sites, revealing that these genes were mainly concentrated in certain cancer-associated biological functions and pathways. In addition, we calculated the differences among clustered methylation sites and performed the specific methylation sites with LASSO algorithm. The selection operator algorithm was employed to derive a risk signature model, and a prognostic signature based on these methylation sites performed well for risk stratification in STSs patients. At last, a nomogram consisted of clinical features and risk score was developed for the survival prediction. This study declares that DNA methylation-based STSs subtype classification is highly relevant for future development of personalized therapy as it identifies the prediction value of patient prognosis.

Retraction Note: Chondro-protective effects of polydatin in osteoarthritis through its effect on restoring dysregulated autophagy via modulating MAPK, and PI3K/Akt signaling pathways.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chondroprotective and antiarthritic effects of Daphnetin used in vitro and in vivo osteoarthritis models.

AIMS: Daphnetin (DAP) is a traditional Chinese drug usually used to treat cardiovascular diseases. Studies have confirmed the anti-inflammatory, antioxidant, anti-bacterial and insecticidal, anti-tumor and neuro-protective effects of DAP. However, its anti-arthritic potential remains unexplored. The aim of this study is to investigate the in vitro and in vivo chondroprotective effects of DAP. MAIN METHODS: The effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1ß for 24 h. For the in vivo studies, rabbits were randomly divided into groups: a normal control group and osteoarthritis (OA) groups. The OA groups received three different doses of DAP for 4 or 8 weeks. The anti-arthritic effect of DAP was assessed using histopathological examinations, qRT-PCR, western blotting and immunohistochemical analysis. KEY FINDINGS: Both in vitro and in vivo results indicate that DAP exerts a protective effect against IL-1ß in chondrocytes. In vitro, DAP inhibits the expression of IL-6, IL-12, MMP-3, MMP-9 and MMP-13, induced by IL-1ß in rabbit chondrocytes, and stimulates the production of IL-10. The inhibitory effect of DAP on the MMPs is partially regulated by the inhibition of the PI3K/AKT, MAPK and NF-κB signaling pathways. The effect of DAP on OA may be attributed to the suppression of inflammatory factor secretion, chondrocyte apoptosis observed by the decrease in pro-apoptotic Caspase-3 and BAX, and the activation of anti-apoptotic BCL-2. SIGNIFICANCE: DAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.

The therapeutic effects of edaravone on collagen-induced arthritis in rats.

Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen-induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat's body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9 mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase-6, glutathione, and heme oxygenase-1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS-1 increased the expression of the nuclear factor-κB (NF-κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF-ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.