Establishment and application of RNAseq based transcriptome analayis on an archivaed bladder cancer cohort. Overall design: Total RNA profilling 61 archived bladder cancer samples and comparison of 4 pairs of fresh frozen and FFPE bladder cancer samples.
Next-generation RNA sequencing of archival formalin-fixed paraffin-embedded urothelial bladder cancer.
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View SamplesOxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
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