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Comparative pharmacokinetics of six components in normal and rheumatoid arthritis rats after intragastrical administration of Qianghuo Shengshi Decoction granules by LC-MS/MS

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Chinese Herbal Medicines 2024年第3期16卷 457-465页

作者： Xin Li Min Wang Yuhong Zhong Qianqian Yin Zheming Hu Wenli Tian Zhongyan Liu Zhidong Liu Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique Ministry of EducationTianjin University of Traditional Chinese Medicine State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese Medicine Haihe Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese Medicine

Objective:To investigate the plasma pharmacokinetics of six representative components(nodakenin,osthole,5-0-methylvisammioside,ferulic acid,liquiritigenin,and liquiritin),which were the ingredients of Qianghuo Shengshi Decoction(QSD) granules,in normal and rheumatoid arthritis(RA) rats administrated QSD granules ***:A rapid and accurate ultra-high performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was developed for the simultaneous determination of six components in plasma,and it showed a good specificity,linearity,intra-day and inter-day precision,intra-day and inter-day accuracy,extraction recovery,stability,and the less matrix ***:The validated LC-MS/MS method was successfully used to compare the plasma pharmacokinetics of six ingredients between normal and RA rats after intragastrical administration of QSD granules and differences in the pharmacokinetics were found in two types of *** absorption rate in the RA rats was lower for nodakenin,osthole,5-0-methylvisammioside,liquiritigenin and liquiritin than in the normal group,while the absorption rate of ferulic acid remained constant in two *** comparison with the normal rats,the exposure concentration of nodakenin was higher and that of other five components except for nodakenin was lower under pathological ***,the absorptive amount of nodakenin,osthole,5-0-methylvisammioside and liquiritin was increased and that of ferulic acid and liquiritigenin was reduced in the RA rats than in the normal *** with the normal rats,the retention time of nodakenin,ferulic acid and liquiritin was reduced in vivo,whereas the retention time of osthole,5-0-methylvisammioside and liquiritigenin was raised in the body for the RA *** contrast to the normal rats,the data demonstrated an increase in the elimination velocity of nodakenin and a decrease in the elimination velocity of the other five components except for nodakenin in the pa

关键词： LC-MS/MS pharmacokinetics Qianghuo Shengshi Decoction granules rheumatoid arthritis

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N-Glycosylated type Ⅱ collagen peptides as therapeutic saccharide vaccines for rheumatoid arthritis

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Chinese Chemical Letters 2024年第5期35卷 197-200页

作者： Dake Liu Shuyan Liu Fanlei Hu Zhongtang Li Zhongjun Li State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Rheumatology and Immunology Peking University People’s HospitalBeijing 100044China

The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with *** this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)*** effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also *** N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory *** glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).

关键词： rheumatoid arthritis TypeⅡcollegan Glycosylation N-Glycosylated altered peptides Saccharide vaccines

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Interleukin 6 and Bone Erosions in rheumatoid arthritis in an African Hospital

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Open Journal of Rheumatology and Autoimmune Diseases 2024年第1期14卷 13-19页

作者： Paul Eloundou Aly Kamissoko Fernando Kempta Francine Same Bebey William Beko’o Ange Ngeuleu William Nguekouo Estelle Megne Suzy Manizou Madeleine Singwe Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Department of Internal Medicine Cité Verte District Hospital Yaounde Cameroon Cameroon CHU Ignace Deen Conakry Guinea Faculty of Medicine University of Dschang Dschang Cameroon Faculty of Medicine and Biomedical Sciences Yaoundé University of Yaoundé I Yaounde Cameroon

Introduction: rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study was to describe plasma IL-6 variations in RA patients at Cité Verte District Hospital (Cameroon). Material and Methods: Descriptive and analytical cross-sectional study from December 1, 2021 to May 31, 2022. We included patients over 18 years old suffering from RA (ACR/EULAR 2010). Patients with an infection were not included. The data collected were age, sex, smoking status, family history, disease duration, disease activity by DAS28, CRP, rheumatoid factor, and plasma level of IL-6. Bone erosion was sought on radiography and ultrasound. Result: We included 31 patients, 25 of whom were women (80.6%). The mean age was 47.27 ± 17.97 years. Disease activity was predominantly moderate (32.3%) and severe (32.3%). Mean IL-6 level was 15.29 ± 2.36 pg/ml (extremes: 11.26 pg/ml and 20.15 pg/ml). IL-6 levels were higher in patients with a history of smoking. Similarly, IL-6 levels were higher in patients with mildly active RA in remission than in moderately and severely active RA. Mean IL-6 levels were significantly higher in patients with erosive RA (16.3 pg/ml VS 14.6 pg/ml). Conclusion: IL-6 levels were significantly elevated in men, weaned smokers and patients with bone erosions.

关键词： rheumatoid arthritis Interleukin 6 Bone Erosion-DAS28 Sub-Saharan Africa

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Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of rheumatoid arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

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Medicinal Plant 2024年第2期15卷 69-73,76页

作者： Wei ZHANG Li WANG Yuxin YANG Rui MA Li WANG Ling HUANG Qiaofeng WAN Department of Pathogenic Biology and Immunology School of Basic MedicineNingxia Medical UniversityYinchuan 750004China Department of Rheumatology Ningxia Medical University General HospitalYinchuan 750003China School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004China

[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by *** blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by *** order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot *** expression of let-7i-3p and PI3K before and after baicalin intervention was detected by ***-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and ***-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of *** attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.

关键词： Baicalin rheumatoid arthritis Human fibroblast like synoviocytes of rheumatoid arthritis NLRP3 inflammasome miRNA Dual-luciferase

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Research progress of local characteristic drugs for treatment of rheumatoid arthritis in Xinjiang

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Pharmacology Discovery 2024年第2期4卷 46-51页

作者： Yan Meng Ling-Rui Wang Shan Cong Li Luo Rheumatology and Immunology Department First Affiliated Hospital of Xinjiang Medical UniversityXinjiang 830063China Rheumatology and Immunology Department Lianyungang Second People's HospitalLianyungang 222002China

rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by *** disease tends to recur,persist,and is difficult to *** pathogenesis of RA is ***,the commonly used treatments for RA—non-steroidal anti-inflammatory drugs(NSAIDs),disease-modifying anti-rheumatic drugs(DMARDs),glucocorticoids,and immunosuppressants—have notable side effects with long-term use and may be ineffective for some ***,it is crucial to find drugs with limited side effects and significant curative ***'s local characteristic drugs have a long history,abundant resources,and are known for their safety and effectiveness in treating *** recent years,many studies have reported on the mechanisms of action and therapeutic effects of Xinjiang's local characteristic drugs on *** article reviews the pathogenesis of RA,as well as the research progress and treatment characteristics of Xinjiang-featured drugs.

关键词： local characteristic drugs in Xinjiang rheumatoid arthritis

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Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy

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Nano Research 2022年第1期15卷 153-161页

作者： Jing Zhong Qin Zhang Zheng Zhang Kexin Shi Yuanchen Sun Teng Liu Jun Lin Kai Yang State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection&School for Radiological and Interdisciplinary Sciences(RAD-X)Collaborative Innovation Center of Radiation Medicine of Jiangsu higher Education InstitutionsSoochow UniversitySuzhou 215123China Department of Orthopaedic Surgery The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China

rheumatoid arthritis(RA)is a common chronic systemic autoimmune *** there are a variety of treatments for RA,the substantial clinical therapies are still limited to disease-modifying anti-rheumatic drugs(DMARD),which would induce obvious side-effect in patients after long-term ***,an uncomplicated drug-induced self-assembly strategy was proposed to fabricate enzyme-loaded albumin *** hydrophobic drug methotrexate(MTX)could induce self-assembly of superoxide dismutase(SOD)and human serum albumin(HSA)to form HSA-SOD-MTX *** intravenous injection,dual-modal imaging including fluorescence imaging or single-photon emission computed tomography(SPECT)/CT imaging exhibits high accumulation of cyanine 5.5(Cy5.5)or 125l labeled HSA-SOD-MTX nanoparticles in the joints of collagen-induced arthritis(CIA)***,using the synergy therapy of SOD enzyme to scavenge the reactive oxygen species(ROS)and MTX to suppress inflammation,HSA-SOD-MTX nanoparticles exhibit excellent therapeutic efficiency of RA in CIA mice compared with the other ***-CT and clinical arthritis score of RA mice further demonstrate that RA symptoms of mice treated with HSA-SOD-MTX nanoparticles is significantly relived,which was further demonstrated by the histological analysis and the inflammatory factors *** synergy therapy of inflammation by MTX and SOD enzyme based on HSA-SOD-MTX nanoparticles show excellent therapeutic effects of RA without inducing obvious side ***,our strategy may further promote the highly efficient therapy of RA using SOD enzyme to scavenge the ROS and decreasing the side-effect of MTX,which may provide the reference for clinical RA treatment.

关键词： albumin superoxide dismutase methotrexate rheumatoid arthritis single-photon emission computed tomography(SPECT)/CT

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Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment

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Nano Research 2023年第8期16卷 11197-11205页

作者： Yuanxin Li Bo Li Gang Wang Juanjuan Su Yilin Qiao Chao Ma Fan Wang Jian Zhu Jingjing Li Hongjie Zhang Kai Liu Huji Xu State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of China Hefei 230026China Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education)Department of ChemistryTsinghua UniversityBeijing 100084China School of Clinical Medicine Tsinghua UniversityBeijing 100084China College of Materials Science and Opto-Electronic Technology University of Chinese Academy of SciencesBeijing 100049China First Medical Centre Chinese PLA General HospitalBeijing 100853China

rheumatoid arthritis(RA)is a relatively common inflammatory disease that affects the synovial tissue,eventually results in joints destruction and even long-term *** Janus kinase inhibitors(Jakinibs)show a rapid efficacy and are becoming the most successful agents in RA therapy,high dosing at frequent interval and severe toxicities cannot be ***,we developed a new type of fully compatible nanocarriers based on recombinant chimeric proteins with outstanding controlled release of *** addition,the fluorescent protein component of the nanocarriers enabled noninvasive fluorescence imaging of RA lesions,thus allowing real-time detection of RA *** rat models,the nanotherapeutic is shown to be superior to free upadacitinib,as indicated by extended circulation time and sustained ***,this nanosystem possesses an ultralong half-life of 45 h and a bioavailability of 4-times higher than pristine upadacitinib,thus extending the dosing interval from one day to 2 *** effects such as over-immunosuppression and leukocyte levels reduction were significantly *** smart strategy boosts efficacy,safety and visuality of Jakinibs in RA therapy,and potently enables customized designs of nanoplatforms for other therapeutics.

关键词： engineered protein nanocarrier controlled release bioefficacy rheumatoid arthritis

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A biomimetic adipocyte mesenchymal stem cell membrane-encapsulated drug delivery system for the treatment of rheumatoid arthritis

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Nano Research 2023年第8期16卷 11401-11410页

作者： Chaoyu Gu Shaoying Yang Xuesong Liu Yi Jin Ye Yu Liangjing Lu Department of Rheumatology Ren Ji HospitalShanghai Jiao Tong University School of MedicineShanghai 200000China Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantong 226001China

rheumatoid arthritis(RA)is a chronic,progressive,and inflammatory systemic autoimmune *** drug therapy for RA is hindered by severe side effects due to inefficient delivery to the disease site and broad drug *** by biomimetic biology,this study developed a drug delivery system of adipose-derived mesenchymal stem cell membrane-encapsulated nanoparticles for the treatment of *** intact adipose-derived mesenchymal stem cell(ADSC)membrane was coated on poly(lactic-co-glycolic acid)(PLGA)nanoparticles and loaded with tacrolimus(FK506),a T cell *** ADSC membrane encapsulated on nanoparticles retains the original homing properties of ADSC,targeting the inflamed joints and enhancing tacrolimus anti-inflammatory *** in vitro and in vivo experiments proved that the synergistic effect of the ADSC-membrane and tacrolimus effectively inhibited inflammation in vivo and reduced the expression of pro-inflammatory factors(IL-1β,IL-6,tumor necrosis factor-α(TNF-α)),and increased the expression of anti-inflammatory factors(IL-10).In addition,collagen-induced arthritis(CIA)model results also showed that the drug delivery system could effectively reduce the destruction of articular cartilage and bone in mice without causing any adverse *** study provided a new biomimetic targeting strategy to reshape the inflammatory microenvironment by modulating T cell subsets,providing new inspiration for RA treatment.

关键词： adipose mesenchymal stem cell tacrolimus drug delivery system rheumatoid arthritis

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Diffuse lung involvement in rheumatoid arthritis:a respiratory physician’s perspective

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Chinese Medical Journal 2023年第3期136卷 280-286页

作者： Hui Huang Ruxuan Chen Chi Shao Zuojun Xu Paul J.Wolters Department of Pulmonary and Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Pulmonary and Critical Care Medicine University of CaliforniaSan FranciscoCA 94117USA

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis(RA),which is reported to occur in up to 60%to 80%of RA *** complications are the second leading cause of death due to *** there is a wide spectrum of RA-associated respiratory diseases,interstitial lung disease is the most common manifestation and it impacts the prognosis of *** has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease(RA-ILD)and RA-associated respiratory diseases recently,for example,opportunistic pulmonary infectious diseases and toxicity from RA *** a chest physicians’perspective,we will update the diagnosis and treatment of RA-associated ILD,methotrexate-associated lung disease,and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

关键词： Interstitial lung disease Lung Methotrexate pneumonitis Pneumocystis jiroveci pneumonia rheumatoid arthritis

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Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullination via the SP3/PAD4 pathway

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1600-1615页

作者： Changjun Lv Minghui Sun Yilei Guo Wenxin Xia Simiao Qiao Yu Tao Yulai Fang Qin Zhang Yanrong Zhu Yusufu Yalikun Yufeng Xia Zhifeng Wei Yue Dai Department of Pharmacology of Chinese Materia Medica School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis(RA),but the relationship between the two phenomena remains *** explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of *** function and protein citrullination levels in patients with RA and collageninduced arthritis(CIA)mice were *** both neuron-macrophage coculture system and CIA mice,the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases(PADs)was assessed by *** key transcription factors for PAD4 expression were predicted and *** dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial *** cholinergic or alpha7 nicotinic acetylcholine receptor(a7nAChR)deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo,***,the activation deficiency of a7nAChR induced the earlier onset and aggravation of ***,deactivation of a7nAChR increased the expression of PAD4 and specificity protein-3(SP3)in vitro and in *** results suggest that cholinergic dysfunction-induced deficient a7nAChR activation,which induces the expression of SP3 and its downstream molecule PAD4,accelerating protein citrullination and the development of RA.

关键词： rheumatoid arthritis Citrullination Cholinergic dysfunction a7nAChR Peptidylarginine deiminase 4 Specificity protein-3 Collagen-induced arthritis Neuron-macrophage coculture system

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