Plasmapheresis therapy in combination with TNF-α inhibitor and DMARDs: A multitarget method for the treatment of rheumatoid arthritis.

OBJECTIVE: To evaluate the effects of a multitarget method involving plasmapheresis therapy combined with tumor necrosis factor (TNF)-α inhibitor and disease-modifying antirheumatic drugs (DMARDs) on disease activity parameters in the treatment of active rheumatoid arthritis (RA). METHODS: Sixty-five patients with active RA were divided into two groups according to the treatment administered: the plasmapheresis combination therapy group (Plasmapheresis combination group; 38 cases), in which patients received plasmapheresis therapy along with a TNF-α inhibitor (recombinant human tumor necrosis factor-Fc; rhTNFR:Fc; Etanercept biosimilars) and DMARDs, and a TNF-α inhibitor therapy group (biological agent group; 27 cases), in which patients received a TNF-α inhibitor and DMARDs. Clinical parameters were measured before and at 4 and 24 weeks after treatment. RESULTS: ACR20, ACR50, and ACR70 responses at week 4 were achieved in 84.2%, 78.9%, and 60.5% of the patients in the plasmapheresis combination group, respectively, and 74.1%, 55.6%, and 29.6% of the patients in the biological agent group, respectively. The ACR50 and ACR70 response rates were superior in the former than the latter group (p < 0.05). Similar patterns of statistical significance were observed for ACR20, ACR50, and ACR70 responses at week 24 after the treatment. ACR50 responses were achieved in 84.2% patients and ACR70 responses were achieved in 76.3% patients in the plasmapheresis combination group, and these proportions were better than those in the biological agent group (p < 0.05). CONCLUSIONS: The multitarget method combining plasmapheresis, TNF-α inhibitor, and DMARDs for RA therapy was superior to the combination of TNF-α inhibitor for reducing disease activity parameters in patients with active RA.

Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes.

Objective: Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the expression of plasma microRNA-320c (miR-320c) in patients with knee OA and to explore the clinical value and potential mechanism of miR-320c in knee OA. Methods: Forty knee OA patients and 20 healthy controls were enrolled. The levels of plasma miR-320c and plasma inflammatory cytokines were measured by real-time PCR or ELISA. Correlations of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and cytokine levels with the miR-320c expression level were evaluated by Pearson correlation analysis. Then, a receiver operating characteristic (ROC) curve was drawn to analyse the diagnostic value of miR-320c in OA. Finally, the interaction of miR-320c and cAMP responsive element binding protein 5 (CREB5) was determined using a luciferase reporter assay, and the effect of CREB5 on the cAMP pathway was assessed. Results: The expression level of plasma miR-320c was significantly higher in OA patients than in healthy controls (p < 0.05). The increased plasma miR-320c level was positively correlated with the WOMAC score (r = 0.796, p < 0.001) and the plasma interleukin (IL)-1ß (r = 0.814, p < 0.001) and IL-6 (r = 0.695, p < 0.001) levels in patients with OA. ROC curve analysis demonstrated the relatively high diagnostic accuracy of plasma miR-320c for OA. Furthermore, the luciferase reporter assay results showed that miR-320c regulates CREB5 expression by binding to the CREB5 3'-untranslated region. Moreover, suppression of CREB5 significantly reduced the expression levels of c-fos and c-jun. Conclusion: Our results indicate that plasma miR-320c may serve as a potential novel predictor of the severity of knee OA and that miR-320c may play an important role in the pathogenesis of OA through inhibiting the cAMP pathway by targeting CREB5.

Improved whale swarm algorithm for solving material emergency dispatching problem with changing road conditions.

To overcome the problem of easily falling into local extreme values of the whale swarm algorithm to solve the material emergency dispatching problem with changing road conditions, an improved whale swarm algorithm is proposed. First, an improved scan and Clarke-Wright algorithm is used to obtain the optimal vehicle path at the initial time. Then, the group movement strategy is designed to generate offspring individuals with an improved quality for refining the updating ability of individuals in the population. Finally, in order to maintain population diversity, a different weights strategy is used to expand individual search spaces, which can prevent individuals from prematurely gathering in a certain area. The experimental results show that the performance of the improved whale swarm algorithm is better than that of the ant colony system and the adaptive chaotic genetic algorithm, which can minimize the cost of material distribution and effectively eliminate the adverse effects caused by the change of road conditions.

Deep reinforcement learning algorithm for solving material emergency dispatching problem.

In order to solve the problem that the scheduling scheme cannot be updated in real time due to the dynamic change of node demand in material emergency dispatching, this article proposes a dynamic attention model based on improved gated recurrent unit. The dynamic codec framework is used to track the change of node demand to update the node information. The improved gated recurrent unit is embedded between codecs to improve the representation ability of the model. By weighted combination of the node information of the previous time, the current time and the initial time, a more representative node embedding is obtained. The results show that compared with the elitism-based immigrants ant colony optimization algorithm, the solution quality of the proposed model was improved by 27.89, 27.94, 28.09 and 28.12% when the problem scale is 10, 20, 50 and 100, respectively, which can effectively deal with the instability caused by the change of node demand, so as to minimize the cost of material distribution.

Unsupervised monitoring of vegetation in a surface coal mining region based on NDVI time series.

Surface coal mining causes vegetation disturbance while providing an energy source. Thus, much attention is given to monitoring the vegetation of surface coal mining regions. Multitemporal satellite imagery, such as Landsat time-series imagery, is an operational environment monitoring service widely used to access vegetation traits and ensure vegetation surveillance across large areas. However, most of the previous studies have been conducted with change detection models or threshold-based methods that require multiple parameter settings or sample training. In this paper, we tried to analyze the change traits of vegetation in surface coal mining regions using shape-based clustering based on Normalized Difference Vegetation Index (NDVI) time series without multiple parameter settings and sample training. The shape-based clustering used in this paper applied shape-based distance (SBD) to obtain the distance between time series and used Dynamic Time Warping Barycenter Averaging (DBA) to generate cluster centroids. We applied the method to a stack of 19 NDVI images from 2000 to 2018 for a surface coal mining region located in North China. The results showed that the shape-based clustering used in this paper was appropriate for monitoring vegetation change in the region and achieved 79.0% overall accuracy in detecting disturbance-recovery trajectory types.

Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus.

Nucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial reactive oxygen species (mROS), the byproduct of mitochondrial energy generation, serves as an essential mediator to control the activation and differentiation of cells and regulate the antigenicity of oxidized nucleoids within the mitochondria. Recently, clinical trials on normalization of mitochondrial redox imbalance by mROS scavengers and those investigating the recovery of defective mitophagy have provided novel insights into SLE prophylaxis and therapy. However, the precise mechanism underlying the role of oxidative stress-related mitochondrial molecules in skewing the cell fate at the molecular level remains unclear. This review outlines distinctive mitochondrial functions and pathways that are involved in immune responses and systematically delineates how mitochondrial dysfunction contributes to SLE pathogenesis. In addition, we provide a comprehensive overview of damaged mitochondrial function and impaired metabolic pathways in adaptive and innate immune cells and lupus-induced organ tissues. Furthermore, we summarize the potential of current mitochondria-targeting drugs for SLE treatment. Developing novel therapeutic approaches to regulate mitochondrial oxidative stress is a promising endeavor in the search for effective treatments for systemic autoimmune diseases, particularly SLE.

A clinical practice guideline for the screening and assessment of enthesitis in patients with spondyloarthritis.

Objective: The aim of this review is to provide guidance on the selection of approaches to the screening and assessment of enthesitis in patients with spondyloarthritis (SpA). Methods: Twenty-four questions regarding the approaches to the screening and assessment of enthesitis and the implementation details were devised, followed by a systemic literature review. The Grading of Recommendations Assessment, Development, and Evaluation methodology was employed in the development of this guideline, with modifications to evaluate non-interventional approaches under comprehensive consideration of costs, accessibility, and evidence strength. A consensus from the voting panel was required for the inclusion of the final recommendations and the strength of each recommendation. Results: Seventeen recommendations (including five strong recommendations) were included in this guideline. The voting panel expressed unequivocal support for the necessity of screening and assessment of enthesitis in patients with SpA. It was agreed unanimously that symptom evaluation and physical examination should serve as the initial steps to the recognition of enthesitis, whereas Maastricht Ankylosing Spondylitis Enthesitis Score is a reliable tool in both clinical trials and daily medical practice. Ultrasound examination is another reliable tool, with power Doppler ultrasound as an informative addition. Notwithstanding its high resolution, MRI is limited by the costs and relatively low accessibility, whereas radiographs had low sensitivity and therefore should be rendered obsolete in the assessment of enthesitis. PET/CT was strongly opposed in the detection of enthesitis. Conclusion: This guideline provides clinicians with information regarding the screening and assessment of enthesitis in patients with SpA. However, this guideline does not intend on dictating choices, and the ultimate decisions should be made in light of the actual circumstances of the facilities.

[The role of promoter CpG islands methylation of leptin gene in osteoarthritis].

OBJECTIVE: To investigate the effects of 5-Aza-CdR (methylation transferase inhibitor)on the expression levels of leptin gene in chondrocytes and methylation states of leptin promoter region between osteoarthritis (OA) group and control. METHODS: The chondrocytes in osteoarthritis group were treated with 5-Aza-CdR with different doses and time-points, and the expression level of leptin was detected by real-time polymerase chain reaction for picking up the optimum dose and time-point. Next, the chondrocytes in 5 osteoarthritis patients and 5 control patients (amputation due to severe trauma) were treated with 5-Aza-CdR. Lastly, leptin mRNA expression levels in the four groups osteoarthritis and control chondrocytes treated with/without 5-Aza-CdR were measured by real-time PCR and the methylation state of promoter region (-280 - +79) was detected by epitope quantitative DNA methylation analysis. RESULTS: (1) After treating the chondrocytes in OA groups with 10 µmol/L 5-Aza-CdR for 72 h, the mRNA expression levels of leptin were increased significantly. (2) The mRNA expression levels of leptin were significantly different among the four groups (P < 0.05), and the chondrocytes in osteoarthritis groups treated with 5-Aza-CdR showed a marked induction of leptin mRNA expression. (3) Analysis of quantitative methylation data using an unsupervised hierarchical clustering algorithm, showed that methylation patterns of leptin promoter was different between control and osteoarthritis chondrocyte treated with/without 5-Aza-CdR. CONCLUSION: Demethylation of leptin promoter might up-regulate leptin gene expression level and it might contribute to osteoarthritis.

MicroRNA-320c inhibits articular chondrocytes proliferation and induces apoptosis by targeting mitogen-activated protein kinase 1 (MAPK1).

AIM: To clarify the interaction of microRNA-320c (miR-320c) and mitogen-activated protein kinase 1 (MAPK1), and to investigate the effects of miR-320c on articular chondroctye proliferation and apoptosis. METHODS: Lentiviral expression vectors were constructed and dual luciferase assays containing MAPK1 3'-untranslated regions (3'-UTRs) were performed. Small hairpin RNA (shRNA) was utilized to modulate MAPK1 expression. The messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting respectively. Cell Counting Kit-8 and flow cytometry were conducted to detect the proliferation and apoptosis of Human Chondrocyte-articular (HC-a) cells. Besides that, the influences of miR-320c and MAPK1 on MAPK pathway activation were also evaluated. RESULTS: Our data identified MAPK1 as a direct target gene of miR-320c, and miR-320c can negatively regulate MAPK1 expression by directly binding to MAPK1 3'-UTR in HC-a cells. Further functional study displayed that miR-320c overexpression and MAPK1 shRNA significantly suppressed the proliferation of HC-a cells and promoted cell apoptosis. Meanwhile, MAPK1 shRNA could attenuate miR-320c inhibitor promotive effects on HC-a cell proliferation and reverse its inhibitory effect on cell apoptosis. MAPK1 overexpression could rescue the inhibitory effect of miR-320c on HC-a cell proliferation, and weaken the accelerating effect of miR-320c on cell apoptosis. However, neither miR-320c or MAPK1 shRNA regulate the expression of c-JUN, JNK and c-Fos. CONCLUSION: miR-320c inhibits articular chondrocyte proliferation and induces apoptosis by targeting MAPK1, suggesting that miR-320c perhaps participates in the pathogenesis of osteoarthritis and acts as a potential target for the therapeutic treatment of osteoarthritis.

Single-nucleotide polymorphisms and expression of IL23R in Chinese ankylosing spondylitis patients.

The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) in IL23R with ankylosing spondylitis (AS) in Chinese Han population. Six SNPs were selected for analysis in AS patients and controls. The IL23R mRNA expression was detected using RT-PCR. The differences in the genotypes of rs11209032 and the differences in the genotypes and allele frequencies of rs6677188 between cases and controls were significant. The two SNPs rs11209032 and rs6677188 were in strong linkage disequilibrium. Haplotype analysis noted a higher proportion of GAC in cases and a higher proportion of GTC in controls. The patients with AS showed an elevated level of IL23R mRNA in PBMCs. This study suggested that IL23R polymorphisms were associated with susceptibility to AS in the Chinese population and that IL23R may be involved in the development of AS.

Prevalence of bone mineral density loss and potential risk factors for osteopenia and osteoporosis in rheumatic patients in China: logistic regression and random forest analysis.

BACKGROUND: The objective of this study was to explore the prevalence of change in bone mineral density (BMD) and the potential risk factors for osteopenia and osteoporosis in rheumatic patients. METHODS: An analytical cross-sectional study design was carried out. For this study, one thousand and seven rheumatic patients were recruited and further accepted for data collection and blood and BMD tests. The potential risk factors for osteopenia and osteoporosis in rheumatic patients were further analyzed by using both logistic regression analysis and random forest (RF) analysis. RESULTS: 41.1% of the male patients aged 50 years or above and 50.8% of postmenopausal patients were osteoporotic in their lumbar spine. Among these patients, the prevalence of osteoporosis in the femoral neck and total hip was 19.4% and 8.9% in men, and 27.6% and 16.5% in women respectively, while more than half of the rheumatic patients had osteopenia in the femoral neck and total hip. For men younger than 50 years and premenopausal women, BMD were lower than the health population in the femoral neck (16.5% and 18.3% respectively) and the total hip (17.4% and 10.4% respectively). Older age, body mass index (BMI) <18.5 kg/m2, female sex and glucocorticoid use were associated with lower BMD in the lumbar spine, femoral neck, and total hip of patients. In RF analysis, age was ranked as the most important factor for osteopenia in the lumbar spine, femoral neck, and total hip of patients, followed by glucocorticoid use and BMI. CONCLUSIONS: More interventions should be given to osteopenia patients because of the higher prevalence when compared with osteoporosis patients. Older age, BMI <18.5 kg/m2, female sex and glucocorticoid use were associated with lower BMD in rheumatic patients. The results from the logistic regression can be supplemented by random forest analysis.

Erratum to development and formulation of the classification criteria for osteoarthritis.

[This corrects the article DOI: 10.21037/atm-20-4673.].

Guidelines for the diagnosis and treatment of osteoarthritis in China (2019 edition).

Osteoarthritis (OA) is a degenerative disease of middle-aged and elderly people, contributed a higher burden of disease in China and the world. In 2017, under the support of the Rheumatology and Immunology Expert Committee of the Cross-Strait Medical and Health Exchange Association. The objective was to develop an evidence-based diagnosis and treatment guideline for OA in China based on emerging new evidence. The guideline was registered at International Practice Guidelines Registry Platform (IPGRP-2018CN028). The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations, and the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was followed to report the guideline. The guideline provides recommendations for the OA diagnosis, disease risks monitoring and evaluate, treatment purpose and physical, medical and surgical interventions. This guideline is intended to serve as a tool for Chinese clinicians for the best decisions-making on diagnosis and treatment of OA.

Development and formulation of the classification criteria for osteoarthritis.

BACKGROUND: The classification criteria of osteoarthritis (OA) is lack of the support of relevant research evidence and there is no standardized protocol for detailed steps of the development or clinical verification of classification criteria has yet been established. This study aims to describe the development process of the Categorization of Osteoarthritis CHecklist (COACH), which is designed to choose the precise treatment option for patients with OA. METHODS: A multidisciplinary panel was established to gather opinions. We conducted questionnaire survey and literature review to generate and COACH Panel members were invited to review the drafted classification criteria and optimize classification criteria. The final list of items was discussed and reached the agreement by the core group of the panel. RESULTS: Thirty-six experts participated in COACH Panel including rheumatologist (80.6%; 29/36), orthopedist (13.9%; 5/36), methodologist (2.8%; 1/36) and rehabilitation physician (2.8%; 1/36) for classification factors generating and optimizing. The main body of the final classification criteria consists of six types of OA pathogenesis, eight types of medical findings (which can be grouped into two categories), and six types of the location. The final criteria include load-based type, structure-based type, inflammation-based type, metabolic-based type, systemic factor based type and mixed type. CONCLUSIONS: COACH can better help clinicians quickly classify OA patients and help to choose the best treatment option from the aspects of types, findings and locations. What's more, the classification criteria are also helpful to promote the basic medical research and targeted prevention of OA.

Iguratimod ameliorates bleomycin-induced alveolar inflammation and pulmonary fibrosis in mice by suppressing expression of matrix metalloproteinase-9.

AIM: To investigate the potential therapeutic efficacy of iguratimod (IGU) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: A total of 75 C57BL/6 mice were randomly and evenly divided into control group, BLM (5 mg/kg) group, BLM + IGU (90 mg/kg) group, BLM + methylprednisolone (MP, 10 mg/kg) group and BLM + pirfenidone (PF, 100 mg/kg) group. The mice were sacrificed on day 7, 14 and 28. The lung tissue was examined by hematoxylin and eosin staining and Masson staining to evaluate the degree of alveolitis and fibrosis, and serum cytokines were measured. RESULTS: Histopathological results showed that IGU attenuated BLM-induced alveolar inflammation and decreased collagen deposition in lung tissue from day 7 till day 28. Both the pathological alveolitis and fibrosis scores in the drug-treated groups (IGU group, MP group and PF group) were decreased dramatically compared with the BLM group on day 7, 14 and 28 (P < 0.05). There were no statistical significances among these three groups. Cytokine profile showed that IGU decreased the level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6 and matrix metalloproteinase (MMP)-9 which were up-regulated by BLM on day 7, 14 and 28 (P < 0.05). Furthermore, there is a strong correlation between the severity of pulmonary fibrosis and serum MMP-9 levels. CONCLUSION: IGU can decrease BLM-induced pulmonary fibrosis, and the anti-fibrotic effect of IGU is mediated partly via inhibition of MMP-9, which suggests that IGU could potentially be an effective therapeutic strategy for pulmonary fibrosis.

Epidemiology of spondyloarthritis in the People's Republic of China: review of the literature and commentary.

OBJECTIVES: The prevalence of spondyloarthritis (SpA) and its prototype ankylosing spondylitis (AS) varies considerably in different parts of the world. With 20% of the world's population in China, there is potential for a significant disease burden. Eight of the 10 articles providing primary data on the prevalence of SpA in China are in the Chinese language; our objective is to review all 10 articles for English readers. METHODS: Articles were retrieved by search engines in both the English language (www.pubmed.gov) and Chinese language web sites (www.cnki.net). We limited our search to publications of the period 1994 to 2006, and the key words used were (entered as Chinese characters) "prevalence AND spondyloarthropathy," "prevalence AND ankylosing spondylitis," "epidemiology AND spondyloarthropathy," and "epidemiology AND ankylosing spondylitis." For each survey, we examined the number of subjects surveyed, the survey instrument, the criteria used for classifying patients as SpA or AS, and other methodological quality issues. RESULTS: There were 2 AS surveys in the military and 8 surveys in the civilian communities. Overall, the pooled prevalence of AS for the military and civilian communities is 0.24%, 95% confidence interval (CI: 0.17 to 0.32) and 0.23%, 95% CI (0.19 to 0.28), respectively. There is 1 SpA survey in the military and 4 surveys in the civilian communities. The prevalence of SpA in the military survey is 0.45%. The pooled prevalence of SpA from the civilian surveys is 0.93%, 95%CI (0.53 to 1.65). We found that the survey methodology is generally not well reported, giving rise to concerns about the methodological quality and hence validity of the results. CONCLUSION: The prevalence of AS and SpA in China are similar to Caucasians in the U.S. or Europe.

Seronegative spondyloarthropathy--studies from the Asia Pacific region.

Recent therapeutic advances, in particular the use of anti-tumour necrosis factor (anti-TNF) agents, have revived interest in the seronegative spondyloarthropathies (SpA), a group of arthritides characterised by axial skeletal involvement and the absence of rheumatoid factor. The purpose of this article is to review the studies that have been done in the Asia Pacific region, as a broad understanding of the scope and severity of this group of diseases would enable rheumatologists and physicians in this part of the world to better manage their patients. The majority of genetic studies have focused on the associations of HLA-B27 with ankylosing spondylitis (AS) and SpA, while a few studies examined the associations of the CARD, IL-1, LMP2, TAP and TGF with AS. There are a handful of studies on the immunological responses to bacteria and cytokine levels in AS. The onset and clinical features of SpA have been reported from most countries in the region, but no data on patient outcomes, using current measurement tools such as the Bath Ankylosing Spondylitis Disease Activity index (BASDAI), is available. Validation of these instruments of measurement as well as classification criteria in different ethnic populations is necessary where no prior data exist. Future studies will likely be focused on better clinical characterisation of patient cohorts, particularly with regard to the use of currently used measurement tools for disease activity and spinal function and mobility, and the identification of the need for biologic therapy in each country.

Genome-wide DNA methylation analysis of articular chondrocytes identifies TRAF1, CTGF, and CX3CL1 genes as hypomethylated in osteoarthritis.

The aim of this study is to identify osteoarthritis (OA)-associated differentially methylated genes in human articular chondrocytes from patients with OA. DNA methylation profiling of articular chondrocytes from OA patients, rheumatoid arthritis (RA) patients, and controls was performed, and candidate genes were chosen for validation of gene demethylation status. The mRNA expression levels of candidate genes in chondrocytes were detected by real-time quantitative PCR. Chondrocytes from OA and RA group were treated with 5-Aza-2-deoxycytidine (5-Aza), and then the mRNA expression levels were detected. Forty-five genes with significant methylation differences between OA and control group were identified. Tumor necrosis factor receptor-associated factor 1 (TRAF1), connective tissue growth factor (CTGF), and chemokine (C-X3-C motif) ligand 1(CX3CL1) genes were hypomethylated in chondrocytes of OA and RA patients, which verified by bisulfite sequencing analysis. The mRNA expression level of TRAF1 and CTGF was significantly increased in OA and RA group (p < 0.05), while the expression level of CX3CL1 was only increased in OA group (p < 0.05). For the chondrocytes from OA and RA treated with 5-Aza, the mRNA expression level of TRAF1 and CTGF was highly increased (p < 0.05). It is the first time to show that TRAF1, CTGF, and CX3CL1 genes were hypomethylated in OA chondrocytes and have a consistent correlation with mRNA expression, which suggests that epigenetic changes in the methylation status of TRAF1, CTGF, and CX3CL1 contribute to the pathology of OA.

High-throughput screening of chemical libraries for modulators of gene promoter activity of HLA-B2705: environmental pathogenesis and therapeutics of ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a highly heritable disease with HLA-B27 being the strongest susceptible gene. In order to survey the environmental triggers for arthritis development, we used a high-throughput technique to screen the effects of 12,264 chemicals on the HLA-B27 gene promoter. METHODS: Promoter reporter transfectants 293T-HLA-B27 and HeLa-HLA-B27 were tested using robotics with 12,264 chemicals. Chemicals that modulated HLA-B27 promoter activity > 150% or < 40% were selected for further evaluation of IC50/EC50 and cell viability. RESULTS: The primary screening using the 293T-HLA-B27 promoter reporter cell line yielded 5.1% hits that either suppressed (556 chemicals) or enhanced (68 chemicals) the HLA-B27 promoter activity. A secondary reconfirmation screening was carried out with these 624 candidates using HeLa-HLA-B27 promoter reporter cells under several different culture conditions. The yield of positive candidates was 130, of which 47 were derived from natural products. Based on the bio-information of those positive natural products, 21 chemicals were selected for analysis by dose-response IC50/EC50 experiments. Eight compounds showed potential pharmacological activities. Two suppressors are both derived from an herbal medicine (lei gong teng) that has been used for decades to treat immune diseases. The 6 activators all belonged to a group of chemicals known as flavonoids, widely distributed among dietary fruits and vegetables. CONCLUSION: Several common dietary products that contain certain flavonoids might be environmental risk factors for AS; the Chinese traditional herb lei gong teng might be a potential drug for patients who are HLA-B27-positive. These results provide new research directions for the pathogenesis and therapeutics of AS.

Screening disease-associated proteins from sera of patients with rheumatoid arthritis: a comparative proteomic study.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation at the synovial membrane. Although great progress has been made recently in exploring the etiology and pathogenesis of RA, its molecular pathological mechanism remains to be further defined and it is still a great challenge in determining the diagnosis and in choosing the appropriate therapy in early patients. This study was performed to screen candidate RA-associated serum proteins by comparative proteomics to provide research clues to early diagnosis and treatment of RA. METHODS: Sera isolated from 6 RA patients and 6 healthy volunteers were pooled respectively and high-abundance proteins were depleted by Plasma 7 Multiple Affinity Removal System. The protein expression profiles between the two groups were then compared by two-dimensional gel electrophoresis (2-DE) and the proteins over/under-expressed by more than 3-fold were identified by mass spectrometry analysis. To validate the differential expression levels of the identified proteins between the two groups, ELISA was performed in two of the identified proteins in individual sera from 32 RA patients and 32 volunteers. RESULTS: Eight proteins which over/under-expressed in sera of RA patients were identified. Among them, chain A of transthyretin (TTR) was under-expressed, while serum amyloid A protein, apolipoprotein A (ApoA)-IV, ApoA-IV precursor, haptoglobin 2, ceruloplasmin (Cp), immunoglobulin superfamily 22 and HT016 were over-expressed. ELISA test confirmed that Cp expressed remarkably higher while TTR obviously lower in RA group compared with volunteer group. CONCLUSION: There were 8 identified proteins differentially expressed between RA group and volunteer group, which might be candidate RA-associated proteins and might be promising diagnostic indicators or therapeutic targets for RA.