Project description:In order to explore the intervention effect of Tianhezhuifeng liquid extract on rheumatoid arthritis, we constructed an animal model of rheumatoid arthritis We then performed gene expression profiling analysis using data obtained from synovial tissues of typical samples
Project description:Ayurvedic drug formulations Bacopa monnieri and Centella asiatica are known to have neuroprotective effects. These have been traditionally used in the treatment of Alzhemeir’s disease, and other neurological deficits. Using pan neuronal Aβ42 model of Drosophila melanogaster, a mass spectrometry based quantitative proteomic analysis platform was used to generate the data on proteins altered in response to the Aβ42 toxicity and restoration of altered proteins by consumption of aqueous extracts of two Ayurvedic drug formulations Bacopa monnieri and Centella asiatica aqueous extract. Quantitative proteomic analysis resulted in 0.67 million mass spectra corresponding to 2,59,168 peptide-spectrum matches (PSM) mapping to 24,305 non- redundant peptides corresponding to 11,480 Drosophila melanogaster proteins. Proteins were filtered for >3 PSMs, resulting in 9,540 proteins. Flies expressing Aβ42 significantly altered 517 proteins which were involved in maintaining essential neuronal functions. Supplementing flies with Bacopa monnieri or Centella asiatica extract commonly rescued 224 proteins from Aβ42 toxicity, moreover, extract supplemented group significantly altered proteins which were additionally supporting neuronal maintenance in flies with Aβ42 stress.
Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls Bisulphite converted DNA from the Rheumatoid arthritis patients (cases) and normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays
Project description:To investigate the pro-inflammatory and metabolic function of Rheumatoid Arthritis monocyte derived macrophages RNA sequencing was perfomed on polarised healthy and Rheumatoid Arthritis monocyte-derived macrophages
Project description:Rheumatoid factor are autoantibodies that are found in +/- two thirds of patients with rheumatoid arthritis, a chronic autoimmune disease characterized by inflamed, swollen joints. They consist of polyclonal antibodies that target the Fc part of IgG. The antibodies are not highly specific for rheumatoid arthritis and clinical assays to measure rheumatoid factor are poorly harmonized. We studied rheumatoid factor using a mass-spectrometry-based approach in seropositive, seronegative rheumatoid arthritis patients and in disease controls. Rheumatoid factor was captured on Fc coated microwell plates, isolated, digested into peptides and analyzed by liquid chromatography tandem mass spectrometry. Principal component analysis and sparse partial least squares discriminant analysis showed that peptides derived from seropositive rheumatoid arthritis patients clustered away from the controls. Mass spectrometry analysis revealed framework region-derived and variable region-derived peptides that were enriched in rheumatoid factor positive sera. However, mass spectrometry de novo sequencing failed to sequence the majority of unidentified peptides. Furthermore, mass spectrometry analysis revealed different rheumatoid factor isotypes. In addition to IgM, also IgA and IgG isotypes were observed. In conclusion, mass spectrometry is able to capture the complexity and isotypes of rheumatoid factor autoantibodies, but advances in de novo sequencing are needed to fully characterize the variable part of the antibodies.
Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis Two disease conditions (rheumatoid arthritis and osteoarthritis) in comparison to normal donors were investigated. For the two disease groups samples derived from three individual patients and two pools of patients were hybridised.
Project description:Enhanced osteoclast-mediated bone erosion is a prominent hallmark of rheumatoid arthritis. Emerging evidence suggests that this process is facilitated by metabolic dysregulation of osteoclasts. The mitochondrial enzyme aconitate decarboxylase 1 (Acod1, also known as immune responsive gene 1 [Irg1]) serves as a mediator between the metabolic condition and the functional state of different types of cells. Acod1-deficient mice are characterized by enhanced osteoclast differentiation and bone erosion in an inflammatory arthritis model, while therapeutic treatment with the itaconate-derivative 4-octyl-itaconate (4-OI) alleviates the disease phenotype in experimental arthritis. To ascertain the influence of the Acod1-itaconate axis on the genomic transcriptional network of osteoclasts, we performed a whole transcriptome RNA sequencing analysis with fully differentiated osteoclasts from WT and Acod1-deficient mice that were cultured in the presence or absence of 4-OI.