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1.
Horm Metab Res ; 56(6): 455-462, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710215

ABSTRACT

Serum uric acid (UA) and homocysteine (Hcy) are potential biomarkers of systemic lupus erythematosus (SLE). In this study, the expressions of UA and Hcy in SLE patients and the predictive value of these two parameters for lupus nephritis (LN) were studied. A total of 476 SLE patients were recruited to this case-control study, of which 176 SLE patients diagnosed with LN and 300 without LN. Serum UA and Hcy levels were analyzed. Multivariate logistic regression analysis was used to evaluate the relationship between serum UA and Hcy and LN. The receiver operating characteristic (ROC) curves were used to predict the role of combination of serum UA and Hcy in LN. We found that serum UA and Hcy levels in SLE patients with LN were significantly higher than those in controls (p<0.05). Multivariate logistic regressions showed that serum UA (OR+=+1.003, 95+% CI: 1.001-1.006, p+=+0.003), apolipoprotein B (Apo B) (OR+=+21.361, 95+% CI: 2.312-195.373, p+=+0.007) and Hcy (OR+=+1.042, 95+% CI: 1.011-1.080, p+=+0.014) were independent markers of LN. Combined serum UA and Hcy revealed a better result (AUC+=+0.718, 95+% CI: 0.670-0.676, p<0.001) in prediction of LN compared to that of the serum UA (AUC+=+0.710) and Hcy (AUC+=+0.657) independently. In conclusion, serum UA and Hcy could be predictive biomarkers of LN, and joint detection of serum UA and Hcy might be useful in the clinical setting.


Subject(s)
Biomarkers , Homocysteine , Lupus Nephritis , ROC Curve , Uric Acid , Humans , Uric Acid/blood , Homocysteine/blood , Lupus Nephritis/blood , Lupus Nephritis/diagnosis , Female , Biomarkers/blood , Male , Adult , Case-Control Studies , Middle Aged , Prognosis
2.
Clin Rheumatol ; 43(3): 959-969, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38305937

ABSTRACT

OBJECTIVE: Fibroblast-like synoviocytes (FLS) play a critical role on the exacerbation and deterioration of rheumatoid arthritis (RA). Aberrant activation of FLS pyroptosis signaling is responsible for the hyperplasia of synovium and destruction of cartilage of RA. This study investigated the screened traditional Chinese medicine berberine (BBR), an active alkaloid extracted from the Coptis chinensis plant, that regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis. METHODS: First, BBR was screened using a high-throughput drug screening strategy, and its inhibitory effect on RA-FLS was verified by in vivo and in vitro experiments. Second, BBR was intraperitoneally administrated into the collagen-induced arthritis rat model, and the clinical scores, arthritis index, and joint HE staining were evaluated. Third, synovial tissues of CIA mice were collected, and the expression of NLRP3, cleaved-caspase-1, GSDMD-N, Mst1, and YAP was detected by Western blot. RESULTS: The administration of BBR dramatically alleviated the severity of collagen-induced arthritis rat model with a decreased clinical score and inflammation reduction. In addition, BBR intervention significantly attenuates several pro-inflammatory cytokines (interleukin-1ß, interleukin-6, interleukin-17, and interleukin-18). Moreover, BBR can reduce the pyroptosis response (caspase-1, NLR family pyrin domain containing 3, and gasdermin D) of the RA-FLS in vitro, activating the Hippo signaling pathway (Mammalian sterile 20-like kinase 1, yes-associated protein, and transcriptional enhanced associate domains) so as to inhibit the pro-inflammatory effect of RA-FLS. CONCLUSION: These results support the role of BBR in RA and may have therapeutic implications by directly repressing the activation, migration of RA-FLS, which contributing to the attenuation of the progress of CIA. Therefore, targeting PU.1 might be a potential therapeutic approach for RA. Besides, BBR inhibited RA-FLS pyroptosis by downregulating of NLRP3 inflammasomes (NLRP3, caspase-1) and eased the pro-inflammatory activities via activating the Hippo signaling pathway, thereby improving the symptom of CIA.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Berberine , Rats , Mice , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Berberine/pharmacology , Berberine/therapeutic use , Berberine/metabolism , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/metabolism , Synovial Membrane/metabolism , Caspases/metabolism , Caspases/pharmacology , Caspases/therapeutic use , Fibroblasts/metabolism , Cells, Cultured , Cell Proliferation , Mammals
3.
Inflamm Res ; 73(3): 415-432, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38265688

ABSTRACT

BACKGROUND: Mammalian STE20-like kinase 1 (MST1) is involved in the occurrence of cancer and autoimmune diseases by regulating cell proliferation, differentiation, apoptosis and other functions. However, its role and downstream targets in rheumatoid arthritis (RA) remain unclear. METHODS: The model of RA fibroblast-like synoviocytes (RA-FLSs) overexpressing MST1 was constructed by lentiviral transfection in vitro and analyzed the effects of MST1 on apoptosis, migration, invasion, and inflammation of RA-FLSs. The effect of MST1 on joint synovial membrane inflammation and bone destruction was observed in vivo by establishing a rat model of arthritis with complete Freund's adjuvant. RESULTS: MST1 is down-regulated in RA-FLSs, and up-regulation of MST1 inhibits the survival, migration, invasion and inflammation of RA-FLSs. Mechanistically, MST1 inhibits SIRT3/mTOR-signaling pathway, inducing decreased mitochondrial autophagy and increased mitochondrial fission, resulting in mitochondrial morphological abnormalities and dysfunction, and ultimately increased apoptosis. We have observed that activation of MST1 alleviates synovial inflammation and bone erosion in vivo. CONCLUSIONS: MST1 reduces the survival, migration, invasion and inflammation of FLSs by inhibiting the SIRT3/mTOR axis to reduce mitochondrial autophagy and promote mitochondrial division, thereby achieving the potential role of relieving rheumatoid arthritis.


Subject(s)
Arthritis, Rheumatoid , Mitochondrial Diseases , Sirtuin 3 , Synoviocytes , Animals , Rats , Cell Proliferation , Cells, Cultured , Fibroblasts/metabolism , Inflammation/metabolism , Mammals , Sirtuin 3/metabolism , Sirtuin 3/pharmacology , TOR Serine-Threonine Kinases/metabolism
4.
Inflammation ; 47(3): 921-938, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38133702

ABSTRACT

Rheumatoid arthritis (RA) is an enduring, progressive autoimmune disorder. Abnormal activation of fibroblast-like synoviocytes (FLSs) has been proposed as the initiating factor for inflammation of the synovium and bone destruction. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA, histones, and granule proteins, are involved in the development of RA in multiple aspects. Pyroptosis, gasdermin-mediated inflammatory programmed cell death, plays a vital function in the etiopathogenesis of RA. However, the exact mechanism underlying NETs-induced pyroptosis in FLSs of RA and its impact on cellular pathogenic behavior remain undefined. In this study, we demonstrated that gasdermin E (GSDME) expression was upregulated in RA plasma and synoviums, which was positively correlated with the elevated cell-free DNA (cfDNA) and citrullinated histone 3 (Cit H3) levels in the plasma. Additionally, in vitro experiments have shown that NETs triggered caspase 3/GSDME-mediated pyroptosis in RA-FLSs, characterized by decreased cell viability, cell membrane blebbing, and rupture, as well as increased levels of pyroptosis-related proteins and pro-inflammatory cytokines. Again, silencing GSDME significantly inhibited pyroptosis and suppressed the migration, invasion, and secretion of pro-inflammatory cytokines in RA-FLSs. Furthermore, we also found that the nuclear factor-kappa B (NF-κB) pathway, serving as an upstream mechanism, was involved in FLS pyroptosis. In conclusion, our investigation indicated that NETs could induce RA-FLS pyroptosis and facilitate phenotypic transformation through targeting the NF-κB/caspase 3/GSDME axis. This is the first to explore the crucial role of NETs-induced FLS pyroptosis in the progression of RA, providing novel targets for the clinical management of refractory RA.


Subject(s)
Arthritis, Rheumatoid , Caspase 3 , Extracellular Traps , NF-kappa B , Pyroptosis , Synoviocytes , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/metabolism , Humans , Extracellular Traps/metabolism , Pyroptosis/physiology , Synoviocytes/metabolism , Synoviocytes/pathology , NF-kappa B/metabolism , Caspase 3/metabolism , Fibroblasts/metabolism , Fibroblasts/pathology , Signal Transduction , Neutrophils/metabolism , Cells, Cultured , Male , Female , Gasdermins
5.
Front Immunol ; 14: 1275033, 2023.
Article in English | MEDLINE | ID: mdl-38053997

ABSTRACT

Background: The systemic immune-inflammation index (SII) is a cost-efficient indicator for carcinoma prognosis. However, its utility in urothelial carcinoma (UC) prognosis is disputed. This meta-analysis aims to assess SII's prognostic value in UC. Methods: A thorough search of databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus, was conducted to find studies until January 11, 2023. Eligibility criteria were applied to select studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies and compiled in a meta-analysis to gauge SII's association with survival outcomes such as overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS). Results: This analysis includes 19 studies with 12505 UC patients. It was found that high SII significantly correlated with worse OS in UC patients (HR 1.430, 95% CI 1.237-1.653, P<0.001). High SII values also linked with poorer CSS (HR 1.913, 95% CI 1.473-2.485, P<0.001), RFS (HR 1.240, 95% CI 1.097-1.403, P=0.001), and PFS (HR 1.844, 95% CI 1.488-2.284, P<0.001) compared to low SII values. Subgroup analysis revealed SII's consistent prognostic value in UC across races, carcinoma types, sample sizes, and SII cut-off values, suggesting its potential as a prognostic indicator in UC patients. Conclusion: Current evidence suggests SII as a promising, cost-efficient predictor in UC patients. This meta-analysis indicates SII's potential as a valuable prognostic tool in UC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307643, identifier CRD42022307643.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/diagnosis , Prognosis , Carcinoma, Transitional Cell/pathology , Inflammation , Proportional Hazards Models
6.
Front Immunol ; 13: 925695, 2022.
Article in English | MEDLINE | ID: mdl-35844557

ABSTRACT

Rheumatoid arthritis(RA) is the most common inflammatory arthritis, and a significant cause of morbidity and mortality. RA patients' synovial inflammation contains a variety of genes and signalling pathways that are poorly understood. It was the goal of this research to discover the major biomarkers related to the course of RA and how they connect to immune cell infiltration. The Gene Expression Omnibus was used to download gene microarray data. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) regression were used to identify hub markers for RA. Single-sample GSEA was used to examine the infiltration levels of 28 immune cells and their connection to hub gene markers. The hub genes' expression in RA-HFLS and HFLS cells was verified by RT-PCR. The CCK-8 assay was applied to determine the roles of hub genes in RA. In this study, we identified 21 differentially expressed genes (DEGs) in RA. WGCNA yielded two co-expression modules, one of which exhibited the strongest connection with RA. Using a combination of differential genes, a total of 6 intersecting genes was discovered. Six hub genes were identified as possible biomarkers for RA after a lasso analysis was performed on the data. Three hub genes, CKS2, CSTA, and LY96, were found to have high diagnostic value using ROC curve analysis. They were shown to be closely related to the concentrations of several immune cells. RT-PCR confirmed that the expressions of CKS2, CSTA and LY96 were distinctly upregulated in RA-HFLS cells compared with HFLS cells. More importantly, knockdown of CKS2 suppressed the proliferation of RA-HFLS cells. Overall, to help diagnose and treat RA, it's expected that CKS2, CSTA, and LY96 will be available, and the aforementioned infiltration of immune cells may have a significant impact on the onset and progression of the disease.


Subject(s)
Arthritis, Rheumatoid , CDC2-CDC28 Kinases , Algorithms , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/genetics , CDC2-CDC28 Kinases/genetics , CDC2-CDC28 Kinases/metabolism , Cell Cycle Proteins/metabolism , Genetic Markers , Humans , Inflammation , Signal Transduction
7.
Transpl Immunol ; 73: 101604, 2022 08.
Article in English | MEDLINE | ID: mdl-35460876

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a common joint disease with abnormal development of human fibroblast-like synoviocytes (HFLS). Circular RNAs (circRNAs) have essential regulation in the disease progression, and this study was to explore the regulatory mechanism of circ_0088036 in RA. METHODS: RNA expression analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. Cell experiments were conducted by Cell Counting Kit-8 assay for cell viability, EdU (5-ethynyl-2'-deoxyuridine) assay for proliferation and flow cytometry for cell cycle or apoptosis. The protein detection was conducted using western blot. Enzyme-linked immunosorbent assay (ELISA) was used to examine the inflammatory cytokines. The binding identification was carried out through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. RESULTS: The level of circ_0088036 RNA was significantly upregulated in sera and in HFLS cells of RA patients. Targeted silencing of circ_0088036 restrained proliferation, cell cycle progression and inflammatory reaction through promoted the apoptosis of HFLS-RA cells via inhibiting the NF-κB pathway. The miR-1263 was identified as a target of circ_0088036. MiR-1263 was found to be down-regulated in sera and in HFLS cells of RA patients. The regulatory effects of circ_0088036 on HFLS-RA cells were attributed to inhibit the miR-1263 level. REL is a susceptibility locus for certain autoimmune diseases. MiR-1263 directly targeted REL, which was discovered to be elevated in sera and HFLS cells of RA patients, and circ_0088036 interacted with miR-1263 to affect REL expression. Functionally, overexpression of miR-1263 suppressed the development of HFLS-RA by blocking the NF-κB pathway, and this phenomenon was reversed by the upregulation of REL. CONCLUSION: These findings suggested that circ_0088036/miR-1263/REL/NF-κB pathway was involved in the functional development of HFLS-RA cells, indicating a novel molecular network in RA progression in vitro.


Subject(s)
Arthritis, Rheumatoid , MicroRNAs , Synoviocytes , Apoptosis , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Cell Proliferation/genetics , Cells, Cultured , Fibroblasts , Humans , Inflammation/metabolism , MicroRNAs/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , Synoviocytes/metabolism
8.
World J Clin Cases ; 10(4): 1286-1290, 2022 Feb 06.
Article in English | MEDLINE | ID: mdl-35211561

ABSTRACT

BACKGROUND: Primary Sjögren's syndrome (pSS) concomitant with autoimmune hemolytic anemia (AIHA) but without eye and mouth dryness is exceedingly rare. Iguratimod (IGU) has been widely used in the treatment of pSS. However, there are few reports about the application of IGU in pSS concomitant with AIHA. CASE SUMMARY: Here, we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness. The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed, and was finally diagnosed with pSS concomitant with AIHA. The patient was treated with IGU along with prednisone and hydroxychloroquine, and her hemoglobin, reticulocytes and IgG returned to normal levels. CONCLUSION: IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA, and may be a promising therapy for the treatment of this disease.

9.
Horm Metab Res ; 53(4): 257-263, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33694137

ABSTRACT

The association between metabolic syndrome (MetS) and survival outcome after acute coronary syndrome (ACS) remains controversial. This meta-analysis sought to examine the association of MetS with all-cause mortality among patients with ACS. Two authors independently searched PubMed and Embase databases (from their inception to June 27, 2020) for studies that examined the association of MetS with all-cause mortality among patients with ACS. Outcome measures were in-hospital mortality and all-cause mortality during the follow-up. A total of 10 studies involving 49 896 ACS patients were identified. Meta-analysis indicated that presence of MetS was associated with an increased risk of long-term all-cause mortality [risk ratio (RR) 1.25; 95% CI 1.15-1.36; n=9 studies] and in-hospital mortality (RR 2.35; 95% CI 1.40-3.95; n=2 studies), respectively. Sensitivity and subgroup analysis demonstrated the credibility of the value of MetS in predicting long-term all-cause mortality. MetS is associated with an increased risk of long-term all-cause mortality among patients with ACS. However, additional studies are required to investigate the association of MetS with in-hospital mortality.


Subject(s)
Acute Coronary Syndrome/mortality , Metabolic Syndrome/complications , Acute Coronary Syndrome/etiology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Metabolic Syndrome/mortality , Middle Aged , Prognosis , Risk Assessment
10.
J Cell Mol Med ; 24(2): 1658-1669, 2020 01.
Article in English | MEDLINE | ID: mdl-31821687

ABSTRACT

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)-associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR-7 expression was down-regulated in lung tissue of PM group than control group, and NETs further decreased miR-7 expression. TLR9 and Smad2 were up-regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA-treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR-7 and Smad2 in LF. Finally, miR-7-Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM-related ILD, and TLR9-miR-7-Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.


Subject(s)
Extracellular Traps/metabolism , Fibroblasts/metabolism , Lung/pathology , MicroRNAs/metabolism , Polymyositis/pathology , Signal Transduction , Smad2 Protein/metabolism , Toll-Like Receptor 9/metabolism , Animals , Base Sequence , Cell Differentiation , Cell Proliferation , Disease Progression , Female , Histones/metabolism , Humans , Mice, Inbred BALB C , MicroRNAs/genetics , Myofibroblasts/pathology , Peroxidase/metabolism , Rats, Sprague-Dawley
11.
Medicine (Baltimore) ; 98(32): e16682, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31393368

ABSTRACT

Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ±â€Š20.7 mg/day to 55.0 ±â€Š11.1 mg/day after 2-week treatment, and to 3.3 ±â€Š2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients' conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antirheumatic Agents/administration & dosage , Methotrexate/administration & dosage , Still's Disease, Adult-Onset/drug therapy , Administration, Intravenous , Administration, Oral , Adult , Antibodies, Monoclonal, Humanized/pharmacology , Antirheumatic Agents/pharmacology , Drug Therapy, Combination , Female , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Male , Methotrexate/pharmacology , Middle Aged , Prednisone/administration & dosage , Prednisone/adverse effects , Treatment Outcome
12.
Int J Clin Pharmacol Ther ; 57(10): 500-505, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31426902

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of low-dose rituximab in the treatment of hematologic abnormalities in patients with connective tissue disease. MATERIALS AND METHODS: A total of 13 patients with connective tissue disease who did not respond to prednisolone and multiple immunosuppressive agents, or their disease recurred after treatment, were given 100 mg of rituximab only combined with prednisolone once a week for 4 weeks. Then, the therapeutic effects and adverse reactions were respectively observed in the 13 patients. RESULTS: Rituximab showed good and rapid efficacy in the treatment of refractory thrombocytopenia and autoimmune hemolytic anemia caused by systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease. Only 1 patient had urinary tract infection. During 24-month follow-up, disease recurred in 7 patients who still responded to azathioprine/Tripterygium wilfordii. CONCLUSION: Low-dose rituximab has good efficacy and safety in the treatment of hematologic abnormalities in patients with connective tissue disease.


Subject(s)
Connective Tissue Diseases/drug therapy , Rituximab/therapeutic use , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/etiology , Antibodies, Monoclonal, Murine-Derived , Humans , Lupus Erythematosus, Systemic/complications , Sjogren's Syndrome/complications , Thrombocytopenia/drug therapy , Thrombocytopenia/etiology , Treatment Outcome
13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(8): 1118-1122, 2017 Aug.
Article in Chinese | MEDLINE | ID: mdl-28871954

ABSTRACT

Objective To detect the serum levels of IL-25 and IL-17 in rheumatoid arthritis (RA) patients and investigate the potential relationship with bone erosion and concomitant interstitial lung disease (ILD). Methods The study enrolled a total of 117 RA patients and 56 healthy subjects as controls. The serum levels of IL-25 and IL-17 were determined by ELISA, and rheumatoid factor (RF) was detected by turbidimetric immunoassay, anticyclic citrullinated peptide (anti-CCP) antibody as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also tested. ILD was identified on high-resolution computed tomography (HR-CT), the degree of bone erosion was inspected by musculoskeletal ultrasonography, and radiographic grade was graded by Sharp-van der Heijde Score (SHS). Disease activity in RA was scored with the DAS28 and visual analogue scale (VAS). Correlation analysis was used to evaluate the correlations of IL-25 and IL-17 in different groups. Results Compared with healthy control group, the serum levels of IL-25 and IL-17 increased significantly in the patients with RA. Compared with bone erosion negative group, the serum level of IL-25 was higher significantly in bone erosion group. The level of IL-25 was higher in the ILD group of RA patients than the non-ILD group. In addition, there were positive correlations between the serum level of IL-25 and RF-IgG (r=0.285), RF-IgA (r=0.314), RF-IgM (r=0.380). Meanwhile, the serum level of IL-17 had the positive correlations with RF-IgG (r=0.198) and RF-IgM (r=0.273). Both of them had no correlations with anti-CCP antibody. Conclusion The serum level of IL-25 is raised in RA patients with bone erosion and ILD.


Subject(s)
Arthritis, Rheumatoid/immunology , Bone Diseases/immunology , Interleukin-17/blood , Lung Diseases, Interstitial/immunology , Adult , Aged , Anti-Citrullinated Protein Antibodies/blood , Female , Humans , Male , Middle Aged , Rheumatoid Factor/blood
14.
J Zhejiang Univ Sci B ; 18(7): 605-614, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28681585

ABSTRACT

OBJECTIVE: Low-density granulocytes (LDGs) can form neutrophil extracellular traps (NETs) spontaneously and excessively. When peripheral blood mononuclear cells (PBMCs) are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs. METHODS: The percentages of LDGs in PBMCs from 55 patients with dermatomyositis (DM), 15 with polymyositis (PM), 42 with rheumatoid arthritis (RA), 25 with systemic lupus erythematosus (SLE), and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions. RESULTS: Significantly higher LDG percentages were found in PBMCs from patients with DM ((8.41±10.87)%, P<0.0001), PM ((8.41±10.39)%, P<0.0001), RA ((4.05±6.97)%, P=0.0249), and SLE ((7.53±11.52)%, P=0.0006), compared with the controls ((1.28±0.73)%). The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force (RCF) within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs. CONCLUSIONS: The LDG percentage in PBMCs is significantly increased in patients with SLE, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.


Subject(s)
Cell Separation/methods , Granulocytes/cytology , Leukocytes, Mononuclear/cytology , T-Lymphocytes/cytology , Adult , Arthritis, Rheumatoid/blood , Case-Control Studies , Cell Adhesion , Dermatomyositis/blood , Female , Flow Cytometry , Humans , Leukocyte Count , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Neutrophils , Polymyositis/blood
15.
Zhongguo Gu Shang ; 30(6): 576-580, 2017 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-29424183

ABSTRACT

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/therapy , Medicine, Chinese Traditional , Tripterygium , Age Factors , Aged , Humans
16.
Mod Rheumatol ; 27(1): 122-129, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27171278

ABSTRACT

OBJECTIVE: We previously found that neutrophil extracellular traps (NETs) were associated with interstitial lung disease (ILD) in dermatomyositis (DM) patients. However, it is unclear whether low-density granulocytes (LDGs), endowed with enhanced NET formation capabilities, contribute to the pathogenesis of ILD. This study aims to elucidate the relationship between LDGs and DM-associated ILD. METHODS: We recruited 48 DM patients (28 with ILD) as well as 19 healthy volunteers for this study. The percentage of LDGs in peripheral blood mononuclear cells (PBMCs) was ascertained by flow cytometry. Plasma cfDNA was measured by using the Quant-iT PicoGreen dsDNA Kit and plasma LL-37 was tested by using the LL-37 ELISA kit. RESULTS: The percentage of LDGs was 7.1 times higher in DM patients than in healthy controls. LDG percentage was 2.7 times higher in DM patients with ILD than in DM patients without ILD. Additionally, LDG percentage positively correlated with MYOACT lung disease activity scores, and NET/neutrophil-related marker levels (LL-37, cfDNA, MPO, and MMP-8) in the DM group were significantly higher than those in the control group. CONCLUSION: The abnormal increase of LDGs may exacerbate abnormal NET regulation and further contribute to the pathogenesis of ILD in DM patients by abnormally forming NETs.


Subject(s)
Dermatomyositis/blood , Granulocytes/pathology , Leukocytes, Mononuclear/pathology , Lung Diseases, Interstitial/blood , Adult , Biomarkers/blood , Dermatomyositis/complications , Female , Flow Cytometry , Humans , Lung Diseases, Interstitial/complications , Male , Middle Aged
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(9): 1204-1208, 2016 08 20.
Article in Chinese | MEDLINE | ID: mdl-27687651

ABSTRACT

OBJECTIVE: To investigate the potential role of deoxyribonuclease I (DNase I) in the pathogenesis of rheumatoid arthritis (RA). METHODS: DNase I activity was measured by radial enzyme-diffusion method in serum samples from 83 RA patients and 60 healthy volunteers and in the synovial fluid (SF) from 27 RA patients and 38 patients with other inflammatory arthritis. SF cfDNA level was measured with Pico Green Kit, and the correlation among DNase I activity, cfDNA level and clinical parameters of RA patients was analyzed. RESULTS: Serum DNase I activity was significantly lower in RA patients than in the healthy control subjects (0.3065∓0.1436 vs 0.4289∓0.1976 U/mL, P<0.001), and was negatively correlated with ESR (r=-0.2862, P=0.0122), CRP (r=-0.2790, P=0.0184) and neutrophil cell counts (r=-0.287, P=0.011). SF DNase I activity was almost negative in patients with RA, ankylosing spondylitis (AS) and gouty arthritis (GA). SF cfDNA level in RA patients was significantly higher than that in patients with osteoarthritis (100.81∓142.98 vs 18.98∓31.40 µg/mL, P=0.002), but similar to that in patients with AS (45.85∓47.67 µg/mL, P=0.428) and GA (162.95∓97.49 µg/mL, P=0.132). In patients with inflammatory arthritis, SF cfDNA level was positively correlated with ESR (r=0.4106, P=0.0116) and CRP (r=0.5747, P=0.0002). CONCLUSION: Impairment of DNase I activity may be responsible for the enhanced NETs generation and plays a role in the pathogenesis of RA.


Subject(s)
Arthritis, Rheumatoid/enzymology , Deoxyribonuclease I/blood , Deoxyribonuclease I/metabolism , Synovial Fluid/enzymology , Arthritis, Gouty/blood , Arthritis, Gouty/enzymology , Arthritis, Rheumatoid/blood , Case-Control Studies , Humans , Osteoarthritis/blood , Osteoarthritis/enzymology , Spondylitis, Ankylosing/blood , Spondylitis, Ankylosing/enzymology
18.
J Biopharm Stat ; 24(3): 600-7, 2014.
Article in English | MEDLINE | ID: mdl-24697196

ABSTRACT

For paired binary data, McNemar's test is widely used to test marginal homogeneity or symmetry for a 2 by 2 contingency table. In this article, we extend McNemar's test by considering a series of paired binary data in which the series is defined by a stratification factor. We provide a test for testing homogeneous stratum effects. For illustration, we apply our test to a cancer epidemiology study. Finally, we conduct simulations to show that our test preserves the nominal type I error level and evaluate the power of our test under various scenarios.


Subject(s)
Clinical Trials as Topic/statistics & numerical data , Computer Simulation , Matched-Pair Analysis , Models, Statistical , Biomarkers/analysis , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Female , Humans , Odds Ratio
19.
Brain Res ; 1449: 38-45, 2012 Apr 17.
Article in English | MEDLINE | ID: mdl-22373650

ABSTRACT

Previous studies have indicated that central sensitization is a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation and astrocytes play an important role in the central sensitization. The current study investigated the role of amino acid transport system A in central sensitization and hyperalgesia induced by intraplantar injection of formalin in rats. Formalin (5%, 50µl) injected subcutaneously into the unilateral hindpaw pad induced typical biphase nociceptive behaviors, including licking/biting and flinching of the injected paw and an increase of glial fibrillary acid protein (GFAP, an activated astrocyte marker) expression in spinal dorsal horn, and these effects could be attenuated by intrathecal injection of the competitive inhibitor of amino acid system A transporter, methylaminoisobutyric acid (MeAIB, 0.1, 0.3, 0.5, and 0.7mmol), in a dose-dependent manner. Intrathecal injection of vehicle (PBS) had no effect on the formalin-induced nociceptive behaviors and increase of the GFAP. These findings suggest that amino acid transport system A is involved in inflammation-induced nociception, and inhibition of this transporter system results in inhibition of the central sensitization and hyperalgesia.


Subject(s)
Amino Acid Transport System A/metabolism , Central Nervous System Sensitization/physiology , Nociceptive Pain/metabolism , Posterior Horn Cells/metabolism , Animals , Behavior, Animal/drug effects , Central Nervous System Sensitization/drug effects , Dose-Response Relationship, Drug , Glial Fibrillary Acidic Protein/metabolism , Inflammation/metabolism , Male , Nociceptors/drug effects , Nociceptors/metabolism , Pain Measurement/drug effects , Posterior Horn Cells/drug effects , Rats , Rats, Sprague-Dawley , Spinal Cord/drug effects , Spinal Cord/metabolism , beta-Alanine/analogs & derivatives , beta-Alanine/pharmacology
20.
Cell Biol Int ; 36(3): 229-36, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-21954859

ABSTRACT

Mechanotransduction is a complicated process, of which mechanosensation is the first step. Previous studies have shown that the cytoskeleton plays a crucial role in mechanosensation and the mediation of intracellular signal transduction. However, the mechanism of mechanotransduction in the bone remains elusive. Here, we investigated the potential involvement of a novel MAPK (mitogen-activated protein kinase) member, ERK5 (extracellular-signal-regulated kinase 5), in the response of osteoblastic cells to FSS (fluid shear stress). Our results demonstrated that ERK5 was rapidly phosphorylated in pre-osteoblastic MC3T3-E1 cells upon FSS, and the integrity and reorganization of the cytoskeleton were critical in this process, in which the cytoskeleton-dependent activation of FAK (focal adhesion kinase) may be involved in the activation of ERK5 induced by FSS. Moreover, we found that cytoskeletal disruption led to significant down-regulation of ERK5 phosphorylation, but had no effect on ERK5 nuclear localization. Furthermore, the cytoskeleton rapidly reorganized in response to FSS, but long-time fluid load, even at a physiological level, led to cytoskeletal disruption, suggesting that other pathways may be involved in long-term mechanotransduction. Taken together, our data provide new insight into the mechanisms of mechanosensation by highlighting the link between ERK5 activation and cytoskeletal reorganization in osteoblasts undergoing FSS.


Subject(s)
Cytoskeleton/metabolism , Mitogen-Activated Protein Kinase 7/metabolism , Osteoblasts/metabolism , Stress, Mechanical , Animals , Cells, Cultured , Down-Regulation , Mechanotransduction, Cellular , Mice , Mitogen-Activated Protein Kinase 7/genetics
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