Arthritis Research & Therapy最新文献

{"title":"Resistin upregulates fatty acid oxidation in synoviocytes of metabolic syndrome-associated knee osteoarthritis via CAP1/PKA/CREB to promote inflammation and catabolism","authors":"Lu Ding, Jin-Yi Ren, Yi-Fan Huang, Jian-Zeng Zhang, Zi-Ran Bai, Yi Leng, Jun-Wei Tian, Jing Wei, Min-Li Jin, Guan Wang, Xia Li, Xin Qi","doi":"10.1186/s13075-025-03527-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03527-6","url":null,"abstract":"Metabolic Syndrome (MetS), as a syndrome characterized by low-grade inflammation and energy metabolism disorders, is considered to be an important systemic risk factor for knee osteoarthritis (KOA). Our previous study showed that the protein level of serum resistin was positively correlated with the degree of metabolic disorder in MetS-OA. However, whether Resistin promotes the progression of KOA synovitis and the underlying mechanisms remain unclear. This study mainly investigateswhether there were metabolism disorder which promote inflammatory and catabolic phenotype in fibroblast-like synoviocytes (FLS) from KOA patients with MetS (MetS-KOA-FLS), and the roles and mechanisim of resistin in MetS-KOA-FLS. Comparative analysis of synovium and FLS from MetS-associated KOA (MetS-KOA) and non-MetS-associated KOA (nMetS-KOA) of females to detect the differences in inflammation, catabolism and glycolipid metabolism. Serum from MetS-KOA stimulated nMetS-KOA-FLS to detect the effect of MetS microenvironment on inflammation, catabolism and glycolipid metabolism of nMetS-KOA-FLS. Resistin stimulated MetS-KOA-FLS to explore the effect of resistin on inflammation and catabolism of MetS-KOA-FLS and its specific mechanism. Compared with nMetS-KOA-FLS, MetS-KOA-FLS expressed higher inflammatory related factors, catabolic enzymes, and showed stronger adhesive and invasive ability. Resistin was found to be an important factor in the serum and internal environment of MetS-KOA patients, and it mediated the differences in fatty acid oxidation (FAO) between the two groups. Resistin activated the PKA/CREB pathway through CAP1 and upregulated FAO, promoting the inflammatory and catabolic phenotype of MetS-KOA-FLS. This study clarifies the mechanism by which MetS causes synovitis from a metabolic perspective and provides new ideas for further research and treatment of MetS-KOA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive comparative analysis of infrapatellar fat pad morphologies in a longitudinal knee osteoarthritis exploratory study: new insights into its role as an independent prognostic marker","authors":"Jean-Pierre Pelletier, Patrice Paiement, François Abram, Marc Dorais, Jean-Pierre Raynauld, Johanne Martel-Pelletier","doi":"10.1186/s13075-025-03513-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03513-y","url":null,"abstract":"No established markers can effectively phenotype knee osteoarthritis (OA) patients into subgroups. Infrapatellar fat pad (IPFP) morphology data that can forecast disease symptoms, structural changes, and knee replacement (KR) are sparse and conflicting. This 96-month longitudinal exploratory study aimed to identify which IPFP morphological features were the most effective independent prognostic markers against these outcomes. This longitudinal study analyzed 1075 target knees (one knee per participant) from the Osteoarthritis Initiative (OAI) progression cohort. Structural changes include cartilage, bone marrow lesions (BMLs), and joint effusion volumes assessed using automated and quantitative magnetic resonance imaging systems (MRI). The IPFP global and signal (hyper- and hypo-) intensity volumes and areas were assessed using MRI combined with a newly developed, fully automated neuron-driven technology. Symptoms were evaluated using WOMAC scores. Data on KR was obtained from the OAI database. Data were collected at baseline and 12, 24, 48 and 96 months and analyzed using a mixed model for repeated measures (MMRM) or ANCOVA. The baseline characteristics were mild to moderate knee OA. Over time, disease symptoms (WOMAC), cartilage volume, IPFP global and hypointense signal volumes, and maximal and hypointense signal areas decreased (all p≤0.001). Joint effusion and hyperintense signal volume and area increased (both p≤0.001). Associations were found between IPFP morphologies at inclusion and changes in cartilage volume (hypointense and hyperintense volumes, 48, 96 months, p≤0.04), BML volume (global volume 48 months, p=0.05; hyperintense area, 12 months, p≤0.04), and effusion volume (hypointense volume 48 months and hyperintense volume 96 months, p≤0.05). At inclusion, smaller IPFP sizes (below median) were associated with cumulative KR at 96 months (global and hypointense volumes, p≤0.04 and maximum area, p=0.05). This longitudinal exploratory study, leveraging a fully automated technology, highlights that i) IPFP volume (global and both signals) is superior to area metrics in predicting long-term structural changes in OA, and ii) smaller IPFP volume and area are linked with reduced need for KR. These findings provide new insights into the usefulness of IPFP morphology as a predictive biomarker of knee OA outcomes, offering a new approach to stratifying knee OA patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"6 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic analysis and experimental verification reveal expansion of monocyte subsets with an interferon signature in systemic lupus erythematosus patients","authors":"Jimin Zhang, Wuwei Zhuang, Yan Li, Chaoqiong Deng, Jingxiu Xuan, Yuechi Sun, Yan He","doi":"10.1186/s13075-025-03560-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03560-5","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by chronic inflammation and multi-organ damage. A central factor in SLE pathogenesis is the excessive production of type I interferon (IFN-I), which drives immune dysregulation. Monocytes, key components of the immune system, significantly contribute to IFN-I production. However, their specific roles in SLE remain incompletely understood. This study utilized bioinformatics and statistical analyses, including robust rank aggregation (RRA), DESeq2, and limma, to analyze transcriptome data from peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients and healthy controls. Single-cell RNA sequencing (scRNA-seq) data were processed using the Seurat R package to identify and characterize monocyte subsets with a strong IFN-driven gene signature. Flow cytometry was employed to validate key findings, using markers such as CD14, SIGLEC1, and IRF7 to confirm monocyte subset composition. Our research has found that monocytes in SLE undergo IFN-driven transcriptional reprogramming, with the upregulation of key interferon signature genes (ISGs), forming the SLE-Related Monocyte Signature (SLERRAsignature). Moreover, the composition of mononuclear phagocyte subsets in SLE patients changes, with an increase trend in the proportion of the CD14Mono8 subset in the flare group. The differentially expressed genes (DEGs) in 13 mononuclear phagocyte subsets of SLE are mainly ISGs, and the expression of ISGs is higher in severe patients. We identified SIGLEC1+IRF7+ monocytes among these subsets and for the first time discovered this group of cells in the peripheral blood of healthy individuals. In SLE, the enrichment score of the gene set representing SIGLEC1+IRF7+ monocytes is positively correlated with the severity of SLE. Finally, flow cytometry confirmed that the frequency of CD14+SIGLEC1+IRF7+ monocytes in PBMCs was higher in SLE compared with healthy controls. Our study found that the expansion of IFN-I-producing monocyte subsets, particularly the CD14+SIGLEC1+IRF7+ subset, plays a crucial role in SLE pathogenesis. This subset may serve as a potential biomarker and therapeutic target for managing SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circ_0002970 promotes fibroblast-like synoviocytes invasion and the inflammatory response through Hippo/YAP signaling to induce CTGF/CCN1 expression in rheumatoid arthritis","authors":"Haoran Kong, Yushuang Qiao, Dahu Qi, Shixin Zhao, Zhiming Cao, Junhao Feng, Yitong Li, Yunke Liu, Tao Liu","doi":"10.1186/s13075-025-03562-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03562-3","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, hyperplasia, and joint destruction. Fibroblast-like synoviocytes (FLSs) are key effector cells in RA, contributing to synovial invasion, extracellular matrix degradation, and inflammatory cytokine secretion. Recent studies suggest that circular RNAs (circRNAs) regulate cellular function and disease progression, but their role in RA remains unclear. The Hippo-YAP signaling pathway governs cell proliferation, apoptosis, and extracellular matrix remodeling, and its dysregulation is linked to RA synovial hyperplasia and inflammation. However, whether circRNAs regulate Hippo-YAP signaling in RA-FLSs has not been fully elucidated. This study investigates the role of circ_0002970 in RA progression and its regulation of the Hippo-YAP pathway. Synovial tissues from RA patients, osteoarthritis (OA) patients, and healthy controls were collected. Differentially expressed circRNAs were identified via RNA sequencing. The expression of circ_0002970 was validated via qRT‒PCR, FISH, and RNase R digestion assays. The functional experiments included transfection, migration/invasion assays, ELISA, and Western blotting to evaluate its role in RA-FLSs. Circ_0002970 was significantly upregulated in RA-FLSs. Knockdown of circ_0002970 suppressed RA-FLS migration, invasion, and IL-6 secretion. Mechanistically, circ_0002970 knockdown downregulated the expression of Hippo–YAP pathway components (YAP, CTGF, and CCN1) and decreased the expression of MMP-9 and MMP-13, which are critical for cartilage degradation. Furthermore, verteporfin (VP)-mediated inhibition of Hippo-YAP reversed the effects of circ_0002970 overexpression. These findings highlight circ_0002970 as a novel regulator of RA-FLS migration, invasion, and inflammation via the Hippo-YAP signaling pathway.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent gene signatures and neutrophil enrichment in lymph nodes of inflammatory arthritis patients","authors":"Aoife M. O’Byrne, Janne W. Bolt, Chaja M.J. van Ansenwoude, Martijn van der Heijde, Johanna F. Semmelink, Aldo Jongejan, Perry D. Moerland, Mario Maas, Marleen G.H. van de Sande, Lisa G.M. van Baarsen","doi":"10.1186/s13075-025-03557-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03557-0","url":null,"abstract":"Lymph node (LN) studies in anti-cyclic citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA) patients have revealed notable alterations in adaptive immune cell populations. However, it remains unclear whether similar changes occur in seronegative inflammatory arthritis, such as psoriatic arthritis (PsA) or ACPA-negative RA. This study investigates molecular and cellular alterations in LN biopsies from ACPA-positive RA patients, ACPA-negative inflammatory arthritis (IA) patients, and healthy controls (HCs). Ultrasound-guided LN biopsies were collected from 25 HCs, 14 ACPA positive RA patients and 45 ACPA negative IA patients (including various IA subtypes). Whole LN tissue biopsies were analyzed by transcriptome analyses, quantitative PCR and immunohistochemistry. Distinct LN gene expression profiles were identified in ACPA-positive RA and ACPA-negative IA patients compared to HCs. ACPA-positive RA patients exhibited upregulation of genes associated with adaptive immunity, while ACPA-negative IA patients showed higher expression of genes related to innate immune cell function. Subsequent qPCR analysis confirmed increased mRNA expression of Cathepsin G, a serine protease highly expressed by neutrophils, in ACPA negative IA patients. Immunohistochemistry demonstrated significantly elevated CD15 + neutrophil presence in LNs from IA patients compared to HCs, irrespective of ACPA status and diagnosis (RA or PsA). This study provides novel insights into the immune landscape of lymph nodes in inflammatory arthritis, emphasizing an unexpected role for neutrophils in IA patients. Future research should explore the functional implications of neutrophils within these uninfected lymph nodes to better understand their contribution to the pathogenesis of inflammatory arthritis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"7 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exhausted natural killer cells in adult IgA vasculitis","authors":"Matija Bajželj, Emanuela Senjor, Nika Boštic, Matjaž Hladnik, Snežna Sodin-Šemrl, Milica Perišić Nanut, Janko Kos, Alojz Ihan, Alojzija Hočevar, Andreja Nataša Kopitar, Katja Lakota","doi":"10.1186/s13075-025-03559-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03559-y","url":null,"abstract":"IgA vasculitis nephritis (IgAVN) manifests in up to 84% of adult patients with IgA vasculitis (IgAV) and is associated with an elevated risk of progression to chronic kidney failure. The underlying pathogenic mechanism of adult IgAVN in leukocytes remain largely uncharacterised. Although natural killer (NK) cells were investigated in paediatric IgAV, their specific role in the pathogenesis of adult IgAV has yet to be elucidated. RNA sequencing of leukocytes from adult IgAV patients and healthy controls (HC) was performed. NK cells’ cytotoxicity was assessed using calcein-AM stained K562 cells, and exocytosis was measured by LAMP-1/CD107a expression. Intracellular perforin and granzyme B were analyzed via flow cytometry, and cytokine secretion was measured by Luminex xMAP. Interferon-induced genes were validated with qPCR. Principal component analysis (PCA) of leukocyte gene expression profiles distinguished IgAV patients from HC. Pathway enrichment analysis showed differences in patients’ subsets - Interferon signalling Reactome pathway was observed only in sample from patients with skin-limited IgAV (sl-IgAV) and was confirmed by increased expression of interferon-induced genes using qPCR. Only in samples from IgAVN patients enrichment of NK cell-mediated cytotoxicity KEGG pathway was found. NK cells from IgAVN patients showed significantly decreased cytotoxicity compared to samples from sl-IgAV patients (p = 2.53 × 10− 2). The % of CD107a+-NK cells significantly increased after stimulation in HC (p = 9.7 × 10− 3) and in sl-IgAV patient samples (p = 2.21 × 10− 2) while only a minor increase was observed in samples of IgAVN patients. IgAVN patients exhibited a decreased % of perforin+ NK cells compared to HC. Following phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation, a significant reduction in intracellular perforin level was observed in HC (p = 2.53 × 10− 2), but not in IgAVN patients NK cells. Interferon (IFN)-ϒ and macrophage inflammatory protein (MIP)-1β were significantly decreased in NK cell culture supernatants from IgAVN patients (p = 2.64 × 10− 2 and p = 2.65 × 10− 2 respectively). Patients with IgAVN exhibited impaired cytotoxic and immunomodulatory functions of NK cells, along with a marked absence of interferon signaling in PBMCs. Further studies are needed to confirm if discrimination of patient subsets based on leukocyte samples might be of clinical use and if deregulated NK function might contribute to the pathogenesis of nephritis in adult IgAV.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional brain function study in patients with primary Sjögren’s syndrome","authors":"Chunfeng Hu, Luoyu Wang, Jiao Huang, Yushan Shang, Xiaofang Zhang, Xinyun Du, Huijun Cao, Zhijiang Han, Peiying Wei","doi":"10.1186/s13075-025-03554-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03554-3","url":null,"abstract":"Primary Sjögren’s syndrome (pSS) manifests a spectrum of neuropsychological symptoms, primarily cognitive impairment, but the mechanism of central nervous system damage remains unclear. This study sought to analyze differences in the static and dynamic fractional amplitude of low-frequency fluctuation (fALFF) and region homogeneity (ReHo) between pSS patients and healthy controls (HCs), aiming to elucidate regional brain function alterations and investigate underlying mechanisms. Using stringent inclusion and exclusion criteria, 68 pSS patients and 69 HCs were assessed, including rs-fMRI, neuropsychological assessments, and laboratory tests. Static fALFF (sfALFF), static ReHo (sReHo), dynamic fALFF (dfALFF), and dynamic ReHo (dReHo) were calculated separately using two-sample t-tests to identify differences in brain regions between the two groups. Correlations between these regions and disease duration, laboratory indicators, and neuropsychological test scores were also examined. Static index analysis revealed increased sfALFF in the right supplementary motor area in pSS patients, with significant decreases in sReHo in the left orbital media frontal gyrus, left caudate nucleus, and right precuneus lobe. Dynamic index analysis showed significant increases in dfALFF in the left supplementary motor area and dReHo in the right dorsolateral superior frontal gyrus. Furthermore, sReHo in the right precuneus lobe negatively correlated with NCT-A scores (P = 0.005), and dReHo in the right dorsolateral superior frontal gyrus negatively correlated with DST scores (P = 0.007). PSS patients experience notable changes in regional brain function, as evidenced by alterations in both static and dynamic brain indicators. Integrating these metrics provides a holistic view of the brain function alterations in pSS patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"3 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: efficacy of adipose stromal cells-enriched high-density fat graft combined with BTX-A for Raynaud’s phenomenon: a prospective cohort study","authors":"Chengliang Deng, Xin Liu, Miaomiao Wei, Bihua Wu, Tianhua Zhang, Shune Xiao, Peiru Min, Yixin Zhang","doi":"10.1186/s13075-025-03556-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03556-1","url":null,"abstract":"<p><b>Correction: Arthritis Res Ther 27</b>,<b> 56 (2025)</b></p><p>https://doi.org/10.1186/s13075-025-03533-8</p><p>Following publication of the original article [1], the authors noticed an error in Fig. 1. Specifically, the number of subjects in the control group was incorrectly labelled and should be changed to 9.</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"561\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-025-03556-1/MediaObjects/13075_2025_3556_Fig1_HTML.png\" width=\"685\"/></picture><p>Flow chart of this prospective cohort study</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 2</b></figcaption><picture><img alt=\"figure 2\" aria-describedby=\"Fig2\" height=\"569\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-025-03556-1/MediaObjects/13075_2025_3556_Figa_HTML.png\" width=\"685\"/></picture><p>Flow chart of this prospective cohort study</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>The original article [1] has been updated.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Deng C, Liu X, Wei M, et al. Efficacy of adipose stromal cells-enriched high-density fat graft combined with BTX-A for Raynaud’s phenomenon: a prospective cohort study. Arthritis Res Ther. 2025;27:56. https://doi.org/10.1186/s13075-025-03533-8.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China</p><p>Chengliang Deng, Peiru Min & Yixin Zhang</p></li><li><p>Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China</p><p>Chengliang Deng, Xin Liu, Miaomiao Wei, Bihua Wu, Tianhua Zhang & Shune Xiao</p></li><li><p>The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, China</p><p>Shune Xiao</p></li></ol><span>Authors</span><ol><li><span>Chengliang Deng</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xi","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nocturnal baricitinib administration leads to rapid drug responses in rheumatoid arthritis: a multicenter non-randomized controlled study","authors":"Teppei Hashimoto, Kazuyuki Tsuboi, Takeo Abe, Takahiro Yoshikawa, Kazuteru Noguchi, Tetsuya Furukawa, Koji Tateishi, Yasuhiro Terashima, Nao Sibanuma, Naoto Azuma, Takashi Yamane, Kiyoshi Matsui, Akira Hashiramoto","doi":"10.1186/s13075-025-03555-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03555-2","url":null,"abstract":"Inflammatory cytokine levels exhibit a circadian rhythm in sera, peaking from late night to early morning in patients with rheumatoid arthritis (RA). This cytokine kinetics is a recognized therapeutic target. This clinical study aimed to evaluate the effectiveness of night-time baricitinib administration based on cytokine secretion. In this 52-week multicenter non-randomized controlled study, 122 patients with RA were assigned to four groups: baricitinib 2 mg morning (BAR2MORN), 2 mg evening (BAR2EVE), 4 mg morning (BAR4MORN), or 4 mg evening (BAR4EVE). The primary endpoint was assessed using the 20% improvement in the American College of Rheumatology criteria (ACR20) at week 12. The secondary endpoints were ACR20/50/70 and changes in the clinical disease activity index (CDAI) through 52 weeks. The results were evaluated using the propensity score inverse probability of treatment weighted to reduce selection bias in patient background. BAR4EVE resulted in better primary endpoint improvement than BAR4MORN (78.2 vs. 43.3%; p < 0.001). No difference in improvement was observed in the primary endpoint between BAR2EVE and BAR2MORN (75.5 vs. 60.6%; p = 0.10). However, BAR2EVE demonstrated higher ACR20 at weeks 4, 24, and 52 and ACR50 at weeks 4 and 12 than BAR2MORN. BAR4EVE demonstrated higher ACR20/50 at weeks 4, 8, and 12 and ACR70 at weeks 8, 12, and 24 than BAR4MORN. CDAI changes were significantly reduced in BAR4EVE than in BAR4MORN at weeks 4 and 8. Chronotherapy targeting cytokine secretion resulted in rapid drug response, proposing a new potential application for JAK inhibitors. UMIN000040094, July 1, 2020.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"64 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bulk RNA-seq conjoined with ScRNA-seq analysis reveals the molecular characteristics of nucleus pulposus cell ferroptosis in rat aging intervertebral discs","authors":"Shipeng Chen, Jiawei Fu, Jiang Long, Chang Liu, Xuezheng Ai, Dan Long, Xue Leng, Yang Zhang, Zhengao Liao, Changqing Li, Yue Zhou, Shiwu Dong, Bo Huang, Chencheng Feng","doi":"10.1186/s13075-025-03550-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03550-7","url":null,"abstract":"Recently, several studies have reported that nucleus pulposus (NP) cell ferroptosis plays a key role in IDD. However, the characteristics and molecular mechanisms of cell subsets involved remain unclear. We aimed to define the key factors driving ferroptosis, and the characteristics of ferroptotic NP cells subsets during IDD. The accumulation of iron ions in NP tissues of rats caudal intervertebral discs (IVDs) was determined by Prussian blue staining. Fluorescent probe Undecanoyl Boron Dipyrromethene (C11-BODIPY) and lipid peroxidation product 4-Hydroxynonenal (4-HNE) staining were performed to assess lipid peroxidation level of NP cells. The differentially expressed genes in NP tissues with aging were overlapped with FerrDB database to screen ferroptosis driving genes associated with aging-related IDD. In addition, single cell sequencing (ScRNA-seq) was used to map the NP cells, and further identify ferroptotic NP cell subsets, as well as their crucial drivers. Finally, cluster analysis was performed to identify the marker genes of ferroptotic NP cells. Histological staining showed that, compared with 10 months old (10M-old) group, the accumulation of iron ions increased in NP tissues of 20 months old (20M-old) rats, and the level of lipid peroxidation was also enhanced. 15 ferroptosis driving factors related to IDD were selected by cross-enrichment. ScRNA-seq identified 14 subsets in NP tissue cells, among which the number and ratio of 5 subsets was reduced, and the intracellular ferroptosis related signaling pathways were significantly enriched, accompanied by enhanced cell lipid peroxidation. Notably, ranking the up-regulation fold of ferroptosis related genes, we found Atf3 was always present within TOP2 of these five cell subsets, suggests it is the key driving factor in NP cell ferroptosis. Finally, cluster cross-enrichment and fluorescence colocalization analysis revealed that Rps6 +/Cxcl1- was a common molecular feature among the 5 ferroptotic NP cell subsets. This study reveals that ATF3 is a key driver of NP cell ferroptosis during IDD, and Rps6 +/Cxcl1- is a common molecular feature of ferroptotic NP cell subsets. These findings provide evidence and theoretical support for subsequent targeted intervention of NP cell ferroptosis, as well as provide directions for preventing and delaying IDD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"6 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}