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News from the journal of clinical investigation: may 8, 2012 by ferujkll sdff
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News from the journal of clinical investigation: may 8, 2012 |
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Business,Business News,Business Opportunities
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TITLE: TLR3 deficiency impairs spinal cord synaptic transmission,central sensitization, and pruritus in mice View this article at: articles/view/45414?key=3f9ef13e7d7d649b5580 ONCOLOGY Like sirens at sea, tumors attract and kill immunedefenses For cancer to progress, tumor cells must evade detection and clearance by thebody's defense mechanisms in the immune system. Dr. LeonidMetelitsa and colleagues at the Baylor College of Medicine inHouston, Texas wanted to better understand how immune cells knownas Natural Killer T cells (NKTs) detect tumors and what tumors doto neutralize NKTs. Using a mouse model system, they foundspecialized cells in tumors known as tumor-associated macrophagessecretes molecules that first attract NKTs, but then inhibit NKTcell function and viability.
They further demonstrated thatincreasing expression of a gene called Il15 in NKTs enhanced theactivity of NKTs and reduced the spread of cancer in mice. Theirfindings reveal how tumors can trap and evade the body's immunecells and suggest that the development of therapies that increaseIL15 in NKTs merits further exploration. TITLE: IL-15 protects NKT cells from inhibition by tumor-associatedmacrophages and enhances antimetastatic activity View this article at: articles/view/59535?key=d4bb63659b4c9888cd11 ONCOLOGY NUPR1 regulates pancreatic cancer development in mice Pancreatic cancer is fourth most deadly cancer type worldwide. Patients typicallyhave very few symptoms at early stages, frequently leading todetection at late, advanced stages with a poor prognosis. At thecellular level, pancreatic cancer cells show a remarkableresistance to cellular stress , which may account for such high resistance to treatment.
Dr. JuanLucio Iovanna and colleagues at the Mayo Clinic in Rochester,Minnesota wanted to better understand the molecular basis for thisresistance to cellular stress. The Iovanna team specificallyexamined the role of Nuclear protein 1 (NUPR1), which is elevatedin pancreatic cancer. Using a mouse model of pancreatic cancer,they found that loss of NUPR1 reduces the appearance of cancerouslesions and triggers a cell death. Further, they showed that higherlevels of NUPR1 in pancreatic cancer patients correlated withdecreased survival time.
Their result suggest that the developmentof therapeutics targeting NUPR1 might be provide an effectivetarget for treating pancreatic cancer. TITLE: Nupr1 regulates RelB-dependent events necessary forpancreatic cancer development in mice View this article at: articles/view/60144?key=723af014f0e1b35f03a5 GASTROENTEROLOGY Breaking down barriers The gastrointestinal tract must balance the need to form a barrieragainst foreign pathogens and the need to uptake nutrients from theintestinal lumen. A complex interplay between intestinal epithelialcells and the body's immune cells give rise to the intestinalbarrier. Specialized immune system tissue, known as Peyer'spatches, functions to monitor the microorganisms in the gut,helping to establish tolerance to beneficial organisms and mount adefense against pathogens.
Researchers at the Universit Paris-Diderot in France discovered how one pathogen, Yersiniapseudotuberculosis, exploits molecular pathways in Peyer's patchesto disrupt the intestinal barrier function. Led by Fr d rickBarreau, the research team discovered Y. pseudotuberculos is disrupted the normal transport systems in Peyer's patches tobreak through the intestinal barrier. Moreover, once inside thePeyer's patches, the bacteria infected immune cells and triggeredthe production of a signaling molecule called IL-1 by activatingTLR-2 in immune cells. This immune cell activity triggers a counterresponse in the intestinal epithelial cells that led to the openingof epithelial tight junctions and increased permeability.
Theirresults highlight the intricate interactions between epithelialcells and immune cells during infection and demonstate how Y. pseudotuberculos is subverts these molecular pathways. TITLE: Yersinia pseudotuberculos disrupts intestinal barrier integrity through hematopoietic TLR-2signaling View this article at: articles/view/58147?key=df106eb6bfee3153ced7 HEMATOLOGY Protein disulfide isomerase inhibitors constitute a newclass of antithrombotic agents Protein disulfide isomerase (PDI) is an oxidoreductase that hasrecently been shown to participate in thrombus formation. Whilecurrently available antithrombotic agents inhibit either plateletaggregation or fibrin generation, inhibition of secreted PDI blocksthe earliest stages of thrombus formation, suppressing bothpathways. Since thrombosis and its sequelae remain a leading causeof morbidity and mortality and recurrent thrombosis is commondespite current optimal therapy, we explored extracellular PDI asan alternative target of antithrombotic therapy.
A high throughputscreen identified quercetin-3-rutinoside as an inhibitor of PDIreductase activity in vitro. Inhibition of PDI was selective, asquercetin-3-rutinoside failed to inhibit the reductase activity ofseveral other thiol isomerases found in the vasculature. Usingintravital microscopy, we demonstrated that quercetin-3-rutinosideblocks thrombus formation in vivo by inhibiting PDI. Infusion ofrecombinant PDI reversed the antithrombotic effect ofquercetin-3-rutinoside. Thus, PDI is a viable target for smallmolecule inhibition of thrombus formation, and its inhibition mayprove a useful adjunct in refractory thrombotic diseases notcontrolled with conventional antithrombotic agents.
TITLE: Protein disulfide isomerase inhibitors constitute a newclass of antithrombotic agents View this article at: articles/view/61228?key=656937ff864f2e691a72 Additional References Citations. I am Computer Cables writer, reports some information about aromatic bath salts , natural muscle relaxant.
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