Articles: signal-transducing-adaptor-proteins.
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Aim: Identify variants in RYR1, CACNA1S and STAC3, and predict malignant hyperthermia (MH) pathogenicity using Bayesian statistics in individuals clinically treated as MH susceptible (MHS). Materials & methods: Whole exome sequencing including RYR1, CACNA1S and STAC3 performed on 64 subjects with: MHS; suspected MH event or first-degree relative; and MH negative. Variant pathogenicity was estimated using in silico analysis, allele frequency and prior data to calculate Bayesian posterior probabilities. ⋯ Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Conclusion: Bayesian method provides new approach to predict MH pathogenicity of genetic variants.
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Inflammatory pain hypersensitivity is associated with activation of primary afferent neurons. This study investigated the existence of the inflammasome in dorsal root ganglion (DRG) and the functional significance in the development of inflammatory pain hypersensitivity. Tissue inflammation was induced in male C57BL/6 mice with complete Freund's adjuvant (CFA) or ceramide injection into the hind paw. ⋯ NLRP2 siRNA inhibited ceramide-induced pain hypersensitivity. These results confirmed the existence of NLRP2 inflammasome in DRG neurons. Activation of the NLRP2 inflammasome leads to activation of DRG neurons and subsequent development of pain hypersensitivity in various types of tissue inflammation.
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In vivo and in vitro studies of the role of miR-2355-5p and its possible targets in intervertebral disc degeneration (IVDD). ⋯ N/A.
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Secreted frizzled-related protein 5 (SFRP5) has been reported to be downregulated in prostate cancer. However, its biological role in this malignancy has not been clarified yet. In the present study, we performed SFRP5 overexpression experiments to determine its function in prostate cancer cell growth, invasion, tumorigenesis, and docetaxel sensitivity. ⋯ SFRP5-transfected xenograft tumors showed a reduction in the percentage of Ki-67-positive proliferating cells and an increase in terminal deoxynucleotidyl transferasebiotin-dUTP nick end labeling-positive cells. These data suggest that SFRP5 overexpression suppresses the aggressive phenotype of prostate cancer cells and overcomes docetaxel resistance through inactivation of β-catenin signaling. Therefore, delivery of SFRP5 may offer therapeutic benefits in the treatment of prostate cancer.