BACKGROUND: The molecular events leading to the development of sporadic late-onset Alzheimer's disease (AD) have not been defined. A number of mechanism for the protective effects of non-steroidal anti-inflammatory drugs (NSAIDs) in AD have been proposed. We investigated the ibuprofen effect of global gene expression on the amyloid-beta25-35 (Abeta25-35)-stimulated human astrocytoma cell. METHODS: U373MG, a human astrocytoma cell line, was incubated with 25 microM of aggregated Abeta25-35 or aggregated Abeta25-35 plus 100 microM ibuprofen at 37degrees C for 24 hours. Cells treated with ibuprofen alone were used as the negative control. Differential gene expression analysis was carried out with the Illumina human whole genome microarray. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was also done to validate the gene expression changes. After Welch's t-test, the significant subset of outlier genes were identified by an expression change cut-off 1.5 fold, p<0.05. Kyoto Encyclopedia of Genes and Genomes database was used for cellular signaling pathway analysis. RESULTS: A total of 371 differentially expressed genes were identified from 16,692 detectable signals in Abeta25-35 peptide stimulated U373MG cells- 182 up-regulated genes with 21 biological pathways including biosynthesis of steroid, peroxisome proliferator-activated receptor signaling pathway and focal adhesion and 189 down-regulated genes with 14 biological pathways including transforming growth factor-beta signaling pathway, axon guidance and mitogen activated protein kinase signaling pathway. Ibuprofen suppressed the up-regulated expression of immunity/inflammation (especially, SERPINE1), signal pathway, metabolism and cancer-related genes. The expression of microarray data was confirmed by real-time RT-PCR. CONCLUSION: Aggregated Abeta25-35 induces expression of widespread transcriptional alterations, namely 21 functional groups 182 up-regulated genes and 14 functional groups 189 down-regulated genes in U373MG cells. Ibuprofen, a commonly used NSAID, suppressed Abeta25-35-induced increase of global changes in transcription of sets of genes especially immunity/inflammation, signal pathway, metabolism and cancer-related genes.
Alzheimer Disease ; Amyloid beta-Peptides ; Anti-Inflammatory Agents, Non-Steroidal ; Astrocytoma ; Axons ; Cell Line ; Focal Adhesions ; Gene Expression ; Genome ; Humans ; Ibuprofen ; Oligonucleotide Array Sequence Analysis ; Peptide Fragments ; Peroxisomes ; Protein Kinases ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction

We encountered a patient with systemic lupus erythematosus that manifested as anemia and thrombocytopenia during antithyroid drug treatment. A 39-year-old woman with Graves' disease was admitted with anemia and thrombocytopenia. She had been treated with propylthiouracil, but had switched to methimazole one month prior to admission. We evaluated many possible causes and found that the patient had renal disorder and hematologic disorder, and was positive for antiphospholipid and antinuclear antibodies. She was diagnosed with systemic lupus erythematosus associated with Graves' disease and was successfully treated with corticosteroids.
Adrenal Cortex Hormones ; Adult ; Anemia ; Antibodies, Antinuclear ; Female ; Graves Disease ; Humans ; Lupus Erythematosus, Systemic ; Methimazole ; Propylthiouracil ; Thrombocytopenia

Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH.
Animals ; DNA Methylation/drug effects ; Drug Discovery/methods ; *Epigenesis, Genetic/drug effects ; Genetic Therapy/methods ; Humans ; Hypertension, Pulmonary/*genetics/therapy ; MicroRNAs/*genetics

We encountered a patient with systemic lupus erythematosus that manifested as anemia and thrombocytopenia during antithyroid drug treatment. A 39-year-old woman with Graves' disease was admitted with anemia and thrombocytopenia. She had been treated with propylthiouracil, but had switched to methimazole one month prior to admission. We evaluated many possible causes and found that the patient had renal disorder and hematologic disorder, and was positive for antiphospholipid and antinuclear antibodies. She was diagnosed with systemic lupus erythematosus associated with Graves' disease and was successfully treated with corticosteroids.
Adrenal Cortex Hormones ; Adult ; Anemia ; Antibodies, Antinuclear ; Female ; Graves Disease ; Humans ; Lupus Erythematosus, Systemic ; Methimazole ; Propylthiouracil ; Thrombocytopenia

BACKGROUND: Current dilemma working with surgically-induced OA (osteoarthritis) model include inconsistent pathological state due to various influence from surrounding tissues. On the contrary, biochemical induction of OA using collagenase II has several advantageous points in a sense that it does not involve surgery to induce model and the extent of induced cartilage degeneration is almost uniform. However, concerns still exists because biochemical OA model induce abrupt destruction of cartilage tissues through enzymatic digestion in a short period of time, and this might accompany systemic inflammatory response, which is rather a trait of RA (rheumatoid arthritis) than being a trait of OA. METHODS: To clear the concern about the systemic inflammatory response that might be caused by abrupt destruction of cartilage tissue, OA was induced to only one leg of an animal and the other leg was examined to confirm the presence of systemic degenerative effect. RESULTS: Although the cartilage tissues were rapidly degenerated during short period of time upon biochemical induction of OA, they did not accompanied with RA-like process based on the histology data showing degeneration of articular cartilage occurred only in the collagenase-injected knee joint. Scoring evaluation data indicated that the cartilage tissues in non-induced joint remained intact. Neutrophil count transiently increase between day 8 and day 16, and there were no significant change in other complete blood count profile showing a characteristics of OA disease. CONCLUSION: These study shows that biochemically induced cartilage degeneration truly represented uniform and reliable OA state.
Animals* ; Blood Cell Count ; Cartilage ; Cartilage, Articular ; Clothing ; Collagenases* ; Digestion ; Inflammation ; Joints ; Knee Joint ; Leg ; Models, Animal* ; Neutrophils ; Osteoarthritis* ; Regeneration