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Objective To explore the molecular targets and associated potential pathways of Sinomenii caulis in the treatment of rheumatoid arthritis (RA) based on network pharmacology. Methods The constituents of Sinomenii caulis were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential active ingredients were screened based on oral bioavailability (OB) and drug like index (DL) in TCMSP database. The potential targets of active ingrediens were explored based on DRAR-CPI docking server. RA related gene targets were retrieved through GeneCards and OMIM database. Venn online software was used to obtain the common target of drugs and diseases. The "herbs-compound-target-disease" network diagram was constructed by using Cytoscape software. String database was used to draw the protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the intersection network were conducted by Bioconductor Database. Results 6 active ingredients and 176 targets were identified. 305 target genes directly related to RA were obtained from the GeneCards and OMIM databases. 15 genes were obtained from the intersection of component-target and disease-target. The GO function analysis found 500 items on biological process (BP), 18 items on cellular component (CC), and 28 items on molecular function (MF). KEGG pathway enrichment analysis revealed 77 pathways. Conclusion This study identified six active ingredients from Sinomenii caulis and revealed the key targets of the anti-RA treatment with Sinomenii caulis being IL10、IL4、INS、MAPK8、ELANE、MAPK1 and MAPK14. The important biological processes and signaling pathways including infection, inflammation and immunity were explored. It has laid the foundation for further molecular biology experiments.
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Rheumatoid arthritis ( RA) is a kind of autoimmune disease with high morbidity characterized in synovitis.It has become a key goal for achieving an early RA remission.It is very important for application of RA remission normatively in the treatment of RA.In this paper, comparison and application of various RA remission criteria were reviewed, such as American College of Rheu-matology (ACR), European League Against Rheumatism (EULAR), US Food and Drug Administration (FDA), Outcome Measures in Rheumatoid Arthritis Clinical Trials ( OMERACT) group, ACR /EULAR remission criteria, etc.
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Objective To optimize and establish ELISpot assay for CCP/AST which could secrete IFN-γ and IL-4, and explore the role and clinical significance of CCP/AST cells in occurrence and development of RA disease. Methods CCP was used as specific-stimulator with FLAG peptide as a control,the frequencies of positive SFC which could specifically secrete IFN-γ and IL-4 in 64 cases of RA, 64 cases of non-RA autoinunune diseases and 30 cases of healthy individuals were tested by ELISpot technique. The diagnostic value of CCP/AST cells was evaluated in patients with RA disease. Meanwhile, the relationships among the indexes above and patient joint symptoms as well as other laboratory parameters were further analyzed and discussed. Results The results showed that the mediam numbers of IFN-γ-SFC and IL-4-SFC were 39(12-77)/3 x 105 PBMC and 1 (1-3)/3 × 105 PBMC in RA patients, the positive rates were 81.3% and 18. 8% respectively. The median value of IFN-γ-SFC/IL-4-SFC ratio was of 15(5-39), the positive rate was of 78. 1%. Both IFN-γ-SFC and ratio of IFN-γ-SFC/IL-4-SFC were significantly higher than those of non-RA diseases (Z = - 7. 458, - 7. 019, P < 0. 01 ) and healthy control ( Z = - 6. 643, - 5. 760, P <0. 01 ), also both these parameters in RA patients with positive anti-CCP antibody and negative anti-CCP antibody were significantly higher than those patients with systemic lupus erythematosns ( Z = - 6. 573, - 6. 098, - 4. 552, - 4. 726, P < 0. 01 ), ankylosing spondylitis ( Z = - 3. 520, - 3. 326, - 2. 950,-2. 126, P<0. 01 or 0. 05), other autoimmune diseases (Z = -4. 838, -4. 418, - 3. 681, -3. 839,P < 0. 01 ) and healthy controls ( Z = - 6. 553, - 5. 578, - 4. 635, - 4. 163, P < 0. 01 ). Combining IFN-γ-SFC, IL-4-SFC with IFN-γ-SFC/IL-4-SFC for RA diagnosis, the area under curve of receiver operating characteristic( ROCAUC) and Youden index were 0. 910 and 0. 747. The diagnostic sensitivity and specificity were 87. 5% and 87.2%. Positive and negative predictive values were 82. 4% and 91.1%, respectively. Correlation analysis showed that ratio of IFN-γ-SFC/IL-4-SFC was not only significantly correlated with antiCCP antibody(r =0.393, P <0.01), but also correlated with joint symptoms in patients such as with number of joints swelling-pain ( r = 0. 429 , P < 0. 01 ), number of joints damage ( r = 0. 463, P < 0. 01 ),rheumatoid factor (r = 0. 166, P < 0.01) and erythrocyte sedimentation rate (r=0. 199,P<0.05).Conclusions There is widely existence of CCP/AST cells activation and abnormity in RA patients,indicating higher frequency of CCP-specific Th1 cells. These results provides a new experimental evidence for an objective understanding the function of specific cellular immune responses and cytokine network regulation mediated by citrullinated proteins in RA. So, the assay for CCP/AST cells has potential values in RA diagnosis and clinical application.
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[Objective]To investigate the influence of panax notoginseng saponins(PNS)on production of Nitric Oxide(NO) by peritoneal macrophages of rats with adjuvant arthritis(AA).[Methods]Complete Freund's adjuvant was used to induce AA in rats.Production of NO by peritoneal macrophages of rats with adjuvant arthritis was determined by nitrate reductase.[Results]PNS 0.4mg/ml increased NO synthesis and secretion from peritoneal macrophages of AA rats in vitro after four hours(P
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BACKGROUND: Pressure overload can lead to the activation of reninangiotensin-aldosterone system, and then left ventricular remodeling occurs.Captopril can reverse this progress.OBJECTIVE: To observe the effect of captopril in reversing left ventricular remodeling in rats with pressure overload and to elucidate its possible mechanism.DESIGN: A randomized controlled trial.SETTING: Department of Integrated Traditional Chinese Medicine and Western Medicine, Nanjing General Hospital () Nanjing Military Area Command of Chinese PLA; Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine; Postdoctor Institute of Hebei Medical University.MATERIALS: The experiment was conducted in the Laboratory of Shanghai University of Traditional Chinese Medicine between January 1998 and October 1998. Totally 153 male Wistar rats were recruited.There were 5 experiments, 36 rats in each experiment except 9 rats in the fourth one.METHODS: A total of 36 Wistar male rats selected for each experiment were randomly divided into sham operation group, model group and captopril group. Rats in model group received modeling for 4 weeks, then gastric perfusion with 15 mL/kg of distilled water once per day for 4 consecutive weeks. Abdominal aorta of the rats in sham-operation group were separated without closure by sliver clip, then 4 weeks later the procedure was the same as that in model group. In captopril group, 4 weeks after modeling, the rats were performed gastric perfusion with diluted captopril of 100 mg/kg, once a day for 4 consecutive weeks.MAIN OUTCOME MEASURES: The effect of captopril on left ventricular mass index (LVMI), mRNA expression of collagen type Ⅰ and Ⅲ, content of plasma angiotensin Ⅱ (Ang Ⅱ ) and left ventricular tissue Ang Ⅱ,plasma atrial natriuretic factor (ANF), and serum aldosterone (ALD) level.RESULTS: Totally 153 rats entered the result analysis. During the test for detecting the absorbance (A) of collagen type Ⅰ, 3 rats in sham operation group and 3 in captopril group died, and 1 rat died in model group; finally 29 rats were involved. During the test for detecting the absorbance (A) of collagen type Ⅲ, 3 rats died in sham operation group, 4 rats diedin model group, and 2 rats died in captopril group; finally 27 rats were involved. All in sham operation group and captopril group was lower than that in model group [(2.24±0.12)/1 000, (2.67±0.40)/1 000, (3.15±0.47)/1 000, t=2.649,cantly lower in sham operation group and captopril group than in model group [(0.57±0.19, 0.86±0.25, 2.79±2.00), t=3.661, 3.170, P ＜ 0.01, 0.05].operation group and captopril group than in model group [(0.48±0.10,sion of mRNA of collagen type Ⅰ: It was significantly lower in sham operation group and captopril group than in model group [(79.1 ±18.6)%,plasma Ang Ⅱ content: It was significantly lower in sham-operation group and captopril group than in model group [(130.2±30.2),(137.6±39.5),was significantly lower in sham operation group and captopril group than in model group [(170.6±51.6), (202.5±64.2), (339.3±115.4) μg/L, t=4.623,P ＜ 0.01].type Ⅲ and mRNA expression in rats with pressure overload, suggesting its captopril on left ventricular remodeling might be related to decreasing circulating or local Ang Ⅱ level, plasma ANF and serum aldosterone as well as affecting the expression of collagen type Ⅰ and type Ⅲ mRNA.
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Nuclear factor-?appa B(NF-?B) is an important transcription factor in the expression of any inflammatory media.The role of NF-?B in rheumatoid arthritis has been thought high recently.This review presents the role of NF-?B in rheumatoid arthritis,and the research progression of intervention therapy in inhibition of the activation of NF-?B is also introduced.
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The dendritic cell(DC) has the most powerful function among the antigen presenting cells known hitherto,which stimulates naive T cells and plays a pivotal role in inducing T cell tolerance.The role of DC in rheumatoid arthritis(RA) has aroused more and more attention.This article reviews the role of DC in RA and the researches on the drug intervention in its treatment.
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Objective: To explore the mechanism of high incidence of cardiovascular diseases and the levels of plasma lipids and oxidized lowdensity lipoprotein(Ox-LDL) in patients with rheumatoid arthritis(RA).Methods: Fifty-five patients with RA(24 case of active type,31 non-active) and 60 healthy controls were randomly chosen.Plasma lipids and Ox-LDL levels were studied.All the data were subjected to statistical analysis.Results: Compared with the control,total cholesterol(TC),LDL cholesterol(LDL-C) and apolipoprotein B(apoB) levels were increased in patients with active RA,while TC,triglyceride(TG),LDL-C,apoAⅠ,B and Ox-LDL levels were elevated in those with non-active RA.Furthermore,plasma lipids and Ox-LDL level decreased in the active patients as compared with the non-active ones,while only the change of apoAⅠhad statistical significance.The erythrocyte sedimentation rate was found negatively related with TC,LDL-C,high-density lipoprotein cholesterol(HDL-C) and apoAⅠ,while C-reacting protein was found negatively related with LDL-C and HDL-C.Conclusion: Ox-LDL and plasma lipid levels were changed in RA patients.Inflammation may induce changes of lipoprotein and play an important role in atherosclerosis.
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Objective:To investigate the influential factors correlated to bone mineral density(BMD) in the lumbar vertebra of postmenopausal females,and to find out the influence of body mass and menostasis time on BMD. Methods: BMD in the frontal and lateral lumbar vertebrae of postmenopausal females were measured by dual-energy X-ray absorptiometry(DXA).The correlations of BMD to age,body height,body mass,body mass index(BMI),menopausal age,and/or menopausal years were analyzed using multiple linear regression with SPSS10.0. Results:The change of BMD in the frontal lumbar vertebra was positive to body mass but negatively with postmenopausal years,and that in the lateral lumbar vertebra was closely correlated to BMI. Conclusion: Bone mineral density decreases with increase of menostasis time.Females with a high body mass numerical value have higher bone mineral density.