American journal of translational research
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The knowledge of individual response to a therapy, which can be assesed by in vitro screening, is essential for the development of therapeutics. Chaperone therapy is based on the ability of small molecules to fold the mutant protein to recover its function. As a novel approach for the treatment of Gaucher disease (GD), ambroxol was recently identified as a chaperone for GD, caused by the pathogenic variants in GBA gene, resulting in lysosomal enzyme glucocerebrosidase (GCase) deficiency. ⋯ We showed that PBMCs and macrophages are the most relevant cell-based methods to screen the efficacy of ambroxol therapy. For pediatric patients, a non-invasive source of primary cells, urine derived kidney epithelial cells, have a vast potential for drug screening in GD. These findings demonstrate the importance of personalized screening to evaluate efficacy of chaperone therapy, especially in patients with neuronopathic GD.
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Remote ischemic postconditioning (RIPostC) is an effective strategy for preventing key organs from becoming impaired due to an ischemia/reperfusion injury. In the current study, we investigated how remote exosome transfer of microRNAs (miRs) may contribute to the treatment effect of RIPostC on the central nerve system (CNS). ⋯ Taken together, these results suggest that H/R caused significant changes of miR expression in exosomes derived from H/R-treated HUVECs, and the exosomes protect neurons against H/R-induced injuries by suppressing miR-21-3p.
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Comparing diagnostic accuracy study between ultrasonography (US) guided fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) of the Sentinel lymph nodes (SLNs) in newly diagnosed invasive breast cancer patients. We selected 289 newly diagnosed invasive breast cancer patients from June 2015 to July 2017. Ultrasound (US) guided fine-needle aspiration cytology (FNA) and core-needle biopsy (CNB) was performed to identify patients with suspicious sentinel lymph node (SLN). ⋯ CNB netted 5 false-negative results, and FNAB resulted in 12. There was significantly different accuracy between different diagnostic tools. In our study, we demonstrated that CNB is a more reliable approach than FNA for the preoperative diagnosis of SLN metastasis.
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This study aimed to examine whether exogenous NaHS can protect myocardial mitochondrial injury from sepsis by enhancing the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α)/ nuclear factor erythroid-2-related factor 2 (NRF2) pathway and mitochondrial biosynthesis in mice. Animals were divided into sham-operated, sepsis, sepsis + 25 μmol/L NaHS, sepsis + 50 μmol/L NaHS, sepsis + 100 μmol/L NaHS, and sepsis + 200 μmol/L NaHS groups. ⋯ The adenosine triphosphate (ATP) level was used to appraise the mitochondrial function. The mRNA expression levels of Nrf2, PGC-1α, and Tfam were analyzed to explore the molecular mechanism.
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OPRM1-A118G polymorphism (A > G, rs1799971) is associated with interindividual variability in both response to postoperative pain and opioid treatment. The aim of this meta-analysis is to identify the predictive strength in the current literature of OPRM1-A118G polymorphism to postoperative anesthetic reactions, including nausea, vomiting, pruritus and dizziness. ⋯ OPRM1-A118G polymorphism (A > G) is associated with a reduced risk of postoperative vomiting, but not nausea, pruritus and dizziness. The results should be interpreted with caution due to limited sample and possible heterogeneity between the included studies. Well-designed and large-scale studies are necessary to confirm our results.