Contrast Media & Molecular Imaging
·
2019
·
IF 1.984
Zi Wang,Liang Cai,Tingting Xu,Dan Tang,Lin Liu,Yue Chen
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic, symmetrical, and erosive synovitis. RA is one of the most common disabling diseases in the clinic. The main clinical intervention strategies are early diagnosis and early treatment. This study aims to predict the diagnostic value of 68Ga-citrate and 18F-FDG PET/CT in RA by comparing and analyzing the value of 68Ga-citrate and 18F-FDG PET/CT for diagnosing type II collagen-induced arthritis (CIA) in rats. Some CIA models were established. Normal rats were selected as the control group, and 23 days and 40 days were selected as the early and late time points of arthritis, respectively. The semiquantitative analysis of CIA rats was carried out with 68Ga-citrate PET/CT and 18F-FDG PET/CT, and the ratio of the maximum standardized uptake (SUVmax) values in the regions of interest (ROIs) of the hind foot ankle joint and thigh muscle was calculated and statistically analyzed. The distribution of CIA rats in vivo at the 68Ga-citrate 90 min time point was studied, and the ankle tissues were evaluated with hematoxylin and eosin (HE) staining. 68Ga-citrate PET/CT is obviously superior to 18F-FDG PET/CT for CIA imaging, and the statistical results show that the difference between the two examination methods is statistically significant (). The uptake of these two radiopharmaceuticals showed the same trend in arthritis rats with different scores. The distribution of 68Ga-citrate at 90 min is consistent with the trend shown by 68Ga-citrate PET/CT. 68Ga-citrate PET/CT can reflect the inflammatory activity of affected joints in CIA rats earlier and more sensitively than 18F-FDG PET/CT, and this imaging advantage continues until the later stage of inflammation. Therefore, 68Ga-citrate PET/CT is worthy of further promotion and application in the clinical diagnosis of RA.
研究领域:
医学影像学
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Zixinying Han,Chenxu Liu,Mingrui Li,Mengyan Deng,Ying Ding,Yunchao Li,Meidan Huo,Haiwei Xu,Hailing Qiao,Na Gao
Considerable evidence indicates that CYP2E1 is associated with a variety of inflammatory diseases. Here we evaluated CYP2E1 as a potential therapeutic target for rheumatoid arthritis (RA) and established the protective effect of a new CYP2E1 inhibitor. Gene-expression datasets were used to analyze the change in expression of CYP2E1 in RA patients; CYP2E1 activity in collagen-induced arthritis (CIA) rats was determined by HPLC. We further evaluated the protective effects of C yp2e1 knockout and a CYP2E1-specific inhibitor, Q11, synthesized by our group, in CIA and adjuvant-induced arthritis (AIA) rats. The expression of CYP2E1 in synovial tissue was elevated in RA patients and in CIA rats and the activity of CYP2E1 in vivo and in vitro in CIA rats was greater than that of controls. C yp2e1 knockout significantly reduced the incidence of CIA and alleviated the severity of symptoms. Treatment with different doses of Q11 decreased paw thickness, volume and arthritis scores and reduced the serum levels of IL‐6, TNF‐α, IL‐1β and MDA, and increased the level of GSH in CIA rats. A similar inhibitory effect was exhibited for Q11 in the AIA rats. Moreover, Q11 significantly impeded proliferation, migration, and invasion of human rheumatoid arthritis synovial fibroblasts cells. Q11 decreased the release of ROS and enhanced Nrf2 nuclear translocation and HO-1 expression in the cell nucleus. Overall, our results indicated that CYP2E1 may be a new target for RA and Q11 has potential protective effects against RA by reducing oxidative stress and opposing the inflammatory response via the ROS/Nrf2/HO-1 signaling pathway.
研究领域:
药理学
·
免疫学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR PROBES
·
2016
·
IF 1.565
Xiaoqian Liu,Jingjing Wang,Yi Chu,Xiaoying Zhou
Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease and derived from immune granule cells . It has been suggested playing an important role in the development of rheumatoid arthritis . In this study, a coumarin based fluorescent probe (GF-AFC) was designed and synthesized to evaluate DPPI activity in serum or tissue homogenates of collagen-induced arthritis (CIA) rats, an inflammatory arthropathy model. It was revealed that the fluorescent intensity was significantly increased in a very short time after specific substrate GF-AFC reacted with the DPPI. The fluorophore (AFC) was released to shine after the cleavage reaction which was examined by 19 F NMR spectroscopy. It has been shown that DPPI hydrolyzed the GF-AFC in a robust, linear, and time dependent manner at a significant high rate. A serum-based DPPI activity assay was validated by spiking and gradient dilution methods, there were no interferences or auto-fluorescence observed. The Coefficient of Variance calculated for serum-based DPPI activity assays indicates the good reproducibility. The good correlation has been seen between serum DPPI levels and the severity of arthritis during RA development in CIA rats. Our study has demonstrated a new serum based diagnostic assay for detecting DPPI activity using coumarin conjugated fluorescent (GF-AFC) as a substrate. The successful implementation of the case would provide beneficial experience in rheumatoid arthritis research.
研究领域:
免疫学
·
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Diagnostics
·
2022
·Vol. 12
·期 2
·239
·
IF 3.992
Yingying Xie,Wenwen Chen,Mengqian Zhao,Yuhai Xu,Hao Yu,Jianhua Qin,Hongjing Li
Arthritis is caused by inflammation, infection, degeneration, trauma, or other factors that affect approximately 250 million people all over the world. Early diagnosis and prediction are essential for treatment. Exosomes are nanoscale vesicles that participate in the process of joint disease. Serum is the mainly used sources in the study of arthritis-related exosomes, while whether serum exosomes can reflect the contents of synovial fluid exosomes is still unknown. In this work, we separated exosomes from serum and the synovial fluid of osteoarthritis patients and compared their miRNA expression utilizing miRNA sequencing. The results revealed that 31 upregulated and 33 downregulated miRNAs were found in synovial fluid compared to serum. Transcriptome analysis showed that these differentially expressed miRNAs were mainly associated with intercellular processes and metabolic pathways. Our results show that serum-derived exosomes cannot fully represent the exosomes of synovial fluid, which may be helpful for the study of joint diseases and the discovery of early diagnostic biomarkers of arthritis.Keywords:exosomes;miRNA;synovial fluid;arthritis
研究领域:
生物标志物发现
·
分子生物学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMEMat
·
2024
·
IF 0
He Ren,Zewen Wu,Jingxuan Li,Nan Zhang,Coo Yee Nah,Jiexin Li,Jingyu Zhang,Jonathan F. Lovell,Liyun Zhang,Yumiao Zhang
Rheumatoid arthritis (RA) is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone. RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the joints. Herein, we developed a biomimetic formulation via co-loading the anti-inflammatory agent Celastrol (Cel) along with the stabilizer Vitamin K (VK) in antirheumatic methotrexate (MTX)-conjugated Pluronic F127 (F127) micelles. Micelles were then coated with B cell derived membrane, yielding MTX loaded Cel Micelle (CeViM)-micelle@B, which were investigated for RA treatment. VK, used at levels well within safety margins, was identified as a carrier compound that could stabilize Cel within micelles, increasing the encapsulation efficiency of Cel. In addition, MTX, a front-line RA therapeutic, was chemically grafted to F127 via a responsive linker sensitive to the chemically reducing environments. As such, CeViM-micelle@B released pristine MTX in response to the intracellular reducing environments, which combined with Cel to suppress pro-inflammatory responses. B cell membrane coating enhanced accumulation of CeViM-micelle@B in joints, leading to a 75% decrease of inflammatory cytokine secretion in vitro, and significantly ameliorated cartilage and bone structures in the collagen-induced arthritis murine model. Taken together, this biomimetic nanoparticle holds potential as a next-generation targeted RA treatment.
研究领域:
免疫学
·
药理学
·
纳米医学
·
自身免疫疾病
✓ 已验证
DOI
ACS Omega
·
2022
·
IF 4.132
Shan-Shan Wu,Li-Jun Hao,Yuan-Yuan Shi,Zhuo-Jian Lu,Jia-Lin Yu,Si-Qi Jiang,Qing-Ling Liu,Ting Wang,Shi-Ying Guo,Ping Li,Fei Li
Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine–threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.
研究领域:
药理学
·
中医
·
风湿病学
·
分子生物学
·
系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Drug Delivery
·
2023
·
IF 2.4
Li Chenglong,Lu Guanting,Jiang Yue,Su Huaiyu,Li Chen
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the
global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no
known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor
on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic
distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant
role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune
response and inflammatory cytokine production.
Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions
(NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared
by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2.
Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To
decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the
surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were
investigated by using a laser particle size analyzer and transmission electron microscopy, respectively.
The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation.
In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development
of the mouse arthritis model.
Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had
no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA)
mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as,
anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic
score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory
cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN.
Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work
provides an experimental foundation for expanding the clinical application of EN.
研究领域:
药理学
·
免疫学
·
纳米技术
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AUTOIMMUNITY
·
2024
·
IF 7.9
Qishun Geng,Jiahe Xu,Xiaoxue Cao,Zhaoran Wang,Yi Jiao,Wenya Diao,Xing Wang,Zihan Wang,Mengxiao Zhang,Lu Zhao,Lei Yang,Tingting Deng,Bifa Fan,Yuan Xu,Lansi Jia,Cheng Xiao
Introduction Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood. Materials and methods PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats. Results The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation. Conclusions Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.
研究领域:
免疫学
·
风湿病学
·
药理学
·
细胞生物学
✓ 已验证
DOI
高影响因子
ANNALS OF THE RHEUMATIC DISEASES
·
2024
·
IF 20.3
Fang Qiu,Duoli Xie,Hongzhen Chen,Zhuqian Wang,Jie Huang,Chunhao Cao,Yiying Liang,Xu Yang,Dong-Yi He,Xuekun Fu,Aiping Lu,Chao Liang
Objectives Rheumatoid arthritis (RA) is an autoimmune disease characterised by aggressive fibroblast-like synoviocytes (FLSs). Very few RA patients-derived FLSs (RA-FLSs)-specific surface signatures have been identified, and there is currently no approved targeted therapy for RA-FLSs. This study aimed to screen therapeutic aptamers with cell-targeting and cytotoxic properties against RA-FLSs and to uncover the molecular targets and mechanism of action of the screened aptamers. Methods We developed a cell-specific and cytotoxic systematic evolution of ligands by exponential enrichment (CSCT-SELEX) method to screen the therapeutic aptamers without prior knowledge of the surface signatures of RA-FLSs. The molecular targets and mechanisms of action of the screened aptamers were determined by pull-down assays and RNA sequencing. The therapeutic efficacy of the screened aptamers was examined in arthritic mouse models. Results We obtained an aptamer SAPT8 that selectively recognised and killed RA-FLSs. The molecular target of SAPT8 was nucleolin (NCL), a shuttling protein overexpressed on the surface and involved in the tumor-like transformation of RA-FLSs. Mechanistically, SAPT8 interacted with the surface NCL and was internalised to achieve lysosomal degradation of NCL, leading to the upregulation of proapoptotic p53 and downregulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) in RA-FLSs. When administrated systemically to arthritic mice, SAPT8 accumulated in the inflamed FLSs of joints. SAPT8 monotherapy or its combination with tumour necrosis factor (TNF)-targeted biologics was shown to relieve arthritis in mouse models. Conclusions CSCT-SELEX could be a promising strategy for developing cell-targeting and cytotoxic aptamers. SAPT8 aptamer selectively ablates RA-FLSs via modulating NCL-p53/Bcl-2 signalling, representing a potential alternative or complementary therapy for RA.
研究领域:
免疫学
·
分子生物学
·
治疗学
·
自身免疫疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Fan Chen,Wenzhe Wang,Zian Zhang,Nanyu Pang,Chang Liu,Zhenchao Huang,Haoshen Wu,Haining Zhang
Osteoarthritis (OA), characterized by progressive cartilage degeneration and chronic joint pain, represents a major global health challenge. While intra-articular drug delivery is a common therapeutic approach, its efficacy is limited by poor drug penetration through the dense cartilage matrix, particularly for hydrophobic compounds. Here, a novel charge-guided micro/nanocarrier system designed to overcome these delivery challenges is presented. By modifying amylose with glycidyl trimethyl ammonium chloride (GTAC), it is developed positively charged carriers that demonstrate enhanced penetration into the negatively charged cartilage matrix. The hydrophobic Piezo1 inhibitor, Margaric acid (MA), is efficiently encapsulated within the helical cavity of modified amylose through DMSO-ultrasound treatment, creating Cationic Amylose Micro/Nanocarriers@MA (CAMNC@MA). This system effectively delivers MA to chondrocytes, where Piezo1, a crucial mechanosensor implicated in OA development, can be precisely modulated. These results demonstrate that CAMNC@MA successfully inhibits abnormal mechanical force-induced Piezo1 activation in chondrocytes, enhances cell survival, reduces matrix degradation, and effectively alleviates OA progression. This innovative drug delivery platform offers a promising strategy for clinical OA treatment by combining enhanced matrix penetration with efficient matrix penetration of hydrophobic therapeutic agents.
研究领域:
医学
·
药理学
·
生物材料学
✓ 已验证
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Xiaoxue Cao,Zhaoran Wang,Yi Jiao,Wenya Diao,Qishun Geng,Lu Zhao,Zihan Wang,Xing Wang,Mengxiao Zhang,Jiahe Xu,Bailiang Wang,Tingting Deng,Cheng Xiao
Treg cell-based therapy has exhibited promising efficacy in combatting rheumatoid arthritis (RA). Dihydroartemisinin (DHA) exerts broad immunomodulatory effects across various diseases, with its recent spotlight on T-cell regulation in autoimmune conditions. The modulation of DHA on Treg cells and its therapeutic role in RA has yet to be fully elucidated. This study seeks to unveil the influence of DHA on Treg cells in RA and furnish innovative substantiation for the potential of DHA to ameliorate RA. To this end, we initially scrutinized the impact of DHA-modulated Treg cells on osteoclast (OC) formation in vitro using Treg cell-bone marrow-derived monocyte (BMM) coculture systems. Subsequently, employing the collagen-induced arthritis (CIA) rat model, we validated the efficacy of DHA and probed its influence on Treg cells in the spleen and popliteal lymph nodes (PLN). Finally, leveraging deep proteomic analysis with data-independent acquisition (DIA) and parallel accumulation-serial fragmentation (PASEF) technology, we found the alterations in the Treg cell proteome in PLN by proteomic analysis. Our findings indicate that DHA augmented suppressive Treg cells, thereby impeding OC formation in vitro. Consistently, DHA mitigated erosive joint destruction and osteoclastogenesis by replenishing splenic and joint-draining lymph node Treg cells in CIA rats. Notably, DHA induced alterations in the Treg cell proteome in PLN, manifesting distinct upregulation of alloantigen Col2a1 (Type II collagen alfa 1 chain) and CD8a (T-cell surface glycoprotein CD8 alpha chain) in Treg cells, signifying DHA's targeted modulation of Treg cells, rendering them more adept at sustaining immune tolerance and impeding bone erosion. These results unveil a novel facet of DHA in the treatment of RA.
研究领域:
免疫学
·
风湿病学
·
药理学
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ZEITSCHRIFT FUR RHEUMATOLOGIE
·
2020
·Vol. 81
·期 2
·164-173
·
IF 1.205
Sheng Z.,Zeng J.,Huang W.,Li L.,Li B.,Lv C.,Yan F.
Objective To compare the therapeutic efficacy of paclitaxel (PTX) alone to its combination with methotrexate (MTX) on rheumatoid arthritis. Methods A collagen-induced arthritis (CIA) rat model was established by induction of type II collagen. Rats were divided into blank control group, CIA model group, MTX group 1 mg/kg, PTX 1.5 mg/kg, PTX 2.5 mg/kg, PTX 3.5 mg/kg, and MTX 1 mg/kg + PTX 3.5 mg/kg, with 10 rats per group. The inflammation of the ankle joint was analyzed by H&E staining and interleukin (IL)-1β and IL‑6 expression was detected by immunohistochemistry. TUNEL assay was performed to detect synovial tissue cell apoptosis after administration of PTX and MTX either alone or in combination. TLR4 and p‑NF-κBp65 protein expression in synovial tissue and the changes of serum IL‑1β, IL‑6, IL‑12, MMP‑3, and TNFα protein factors were detected by western blot and ELISA, respectively. Results PTX and MTX improved histopathological changes in CIA rats. Besides, the apoptosis rate of synovial tissue cells in the PTX 3.5 mg/kg group was more than that of the PTX + MTX group. Immunohistochemistry and western blot results indicated that PTX and MTX reduce the expression rate of IL‑6 and IL‑1β and downregulate TLR4 and p‑NF-κBp65 protein expression. Furthermore, TLR4 and p‑NF-κBp65 reduced the concentration of MMP‑3, IL‑12, IL‑6, IL1‑β, and TNFα. Conclusion Both PTX and MTX exert significant suppression on rheumatoid arthritis, and the combined effect of the two drugs is weaker than that of PTX alone. Moreover, intraperitoneal injection of PTX 3.5 mg/kg every other day was the optimal dose observed in this study.
研究领域:
药理学
·
免疫学
·
风湿病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）