Study on Cannabinoid Receptor Expression in Gastrointestinal Diseases
Ontology highlight
ABSTRACT:
DISEASE(S): Crohn's Disease,Ulcerative Colitis,Colon Cancer,Crohn Disease,Colonic Neoplasms
PROVIDER: 2212366 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Autoimmune disease is a systemic inflammatory response of immune blood cells caused by self-tolerance dysfunction, due to genetic or environmental factors or a combination thereof. Studies on autoimmune disease regarding the inhibition of toll-like receptor (TLR)7/9-MyD axis or the regulation of plasmacytoid dendritic cells (pDCs) and Th17 comprising an abundance of respective receptors have shown improvements in phenotypes or molecular markers, providing clues to the practicality of the inhibitors of endosomal TLRs. This study discovered several small-molecule compounds in endosomes exerting specific inhibitory effects on SITE1 shared among TLR 3, 7, 8, and 9, named endosomal TLR inhibitors (ETIs). The drug discovery process involved identifying lead compounds optimized to the receptors using a quantitative structure-activity relationship model and subsequent modification of the compounds to improve their binding affinity to target proteins. To propose a method of verifying the drug effects against side or placebo effect arising from false positives, the drug evaluation process converged from cellular response to signaling process to protein binding. Drug values on the inhibition of endosomal TLRs in autoimmune disease were assessed based on the onset of mild-to-life-threatening autoimmune disease including psoriasis, systemic lupus erythematosus, and multiple sclerosis. Complete healing was achieved for psoriasis through direct or indirect association with TLRs. Therapeutic potential of the novel ETIs for psoriasis was verified and is considered an effective drug for other autoimmune diseases associated with the TLR7/9-MyD axis.
2024-02-29 | GSE255890 | GEO
Project description:Background Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). Methods and Findings Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. Conclusions In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases. Keywords: Sickle cell disease RBC profiling The microRNA of purified erythrocytes from 7 normal and 12 HbSS individuals
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2020-07-15 | PXD015326 | Pride
Project description:Xenobiotic-responsive Nuclear Receptors in Transcriptional Effects Upon Perfluoroalkyl Acid Exposure in Diverse Species
| PRJNA112101 | ENA
Project description:We hypothesized that patients with sarcoidosis have characteristic mRNA profiles. Microarray analysis of gene expression was done on peripheral blood. Comparing peripheral blood from patients with sarcoidosis to controls, 872 transcripts were upregulated and 1039 were downregulated at >1.5-fold change and a significant q value. Several transcripts associated with interferon and STAT1 were upregulated. Lung and lymph node analyses also showed dramatic increases in STAT1 and STAT1-regulated chemokines. Granulomas in lymph nodes of patients with sarcoidosis expressed abundant STAT1 and phosphorylated STAT1. STAT1 might play an important role in sarcoidosis. This novel hypothesis unites seemingly disparate observations with regard to sarcoidosis including implication of a casual role for interferons, a suspected infectious trigger, TH1 predominating lymphocytes in bronchoalveolar lavage, and the association with hypercalcemia. This study tested the hypothesis that SpA is characterized by a distinct pattern of gene expression in peripheral blood of affected individuals compared with healthy controls. High-density, human GeneChip probe arrays were used to profile mRNA of peripheral blood cells from 18 subjects with SpA and 25 normal individuals. Samples were processed as two separate sets at different times. Blood samples were taken at a time when patients were not receiving systemic immunomodulatory therapy. Differential expression was defined as a 1.5-fold change with a q value <5%. Gene ontology and pathway information were also studied. Signals from 134 probe sets (representing 95 known and 12 unknown gene transcripts) were consistently different from controls in both Sets 1 and 2. Included among these were transcripts for a group of 20 genes, such as interleukin-1 receptors 1 and 2, NLRP2, SLPI, SPARC, and TREM-1 that are clearly related to the immune or inflammatory response and a group of 4 transcripts that have a strong role in bone remodeling. Our observations are the first to implicate SPARC, SLPI, and NLRP2, a component of the innate immune system, in the pathogenesis of SpA. Our results also indicate a possible role for interleukin-1 and its receptors in SpA. In accord with the bone pathology component of SpA, we also found that expression levels of transcripts reflecting bone remodeling factors are also distinguishable in peripheral blood from patients with SpA versus controls. These results confirm some previously identified biomarkers implicated in the pathogenesis of SpA and also point to novel mediators in this disease. Peripheral blood was collected from diseased and control subjects. The sarcoidosis portion of the study included 12 patients and 12 control subjects. The spondyloarthropathy study was done in two independent sets. The first set included 11 patients and the same 12 control subjects used for the sarcoidosis study. The second set included 7 patients and 13 control subjects. For each sample, total RNA was isolated and analyzed by hybridization on Affymetrix arrays.
2009-11-04 | E-GEOD-18781 | biostudies-arrayexpress
Project description:Background Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). Methods and Findings Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. Conclusions In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases. Keywords: Sickle cell disease RBC profiling
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Project description:Interventions: Group 1: Colon tissue (tumor, control tissue and tissue from diverticulitis patients) which is optained within a surgical intervention at the Asklepios Paulinen Clinic in Wiesbaden is directly transferred to the Clinic of Pathology of the Helios Dr.-Horst-Schmidt-Clinic Wiesbaden, where it is categorized.
Within 24 h the tissue is collected from a staff of the Insitute of clinical Pharamcology University of Frankfurt.
At the Institute of clinical Pharmacology of the University hospital Frankfurt the tissue is prepared for immunohistochemistry, for detection of lipids by liquid-chromatography-tandem mass spectrometry, for single cell isolation, FACS analysis, and in vitro culture experiments.
Primary outcome(s): Lipid level after stimulation and anti-inflammatory therapy
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: basic science
| 2434471 | ecrin-mdr-crc