American journal of translational research
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Skin wound healing is a challenging problem, especially in aging or diabetic patients, which becomes more difficult to heal, and easily results in considerable public health burden. The purpose of this study was to investigate the effects of metformin on wound healing and explore its underlying mechanism. ⋯ Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing. These findings provided new insights into the molecular mechanism of metformin therapy and its therapeutic potential in wound healing.
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Fabry disease (FD) is a rare X-linked genetic disorder caused by mutations in the GLA gene encoding the lysosomal enzyme, α-galactosidase A (α-gal A). The mutations lead to lack of or faulty enzyme causing accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids including globotriaosylsphingosine (lyso-Gb3). Treatment options for FD include enzyme replacement therapy. ⋯ Further, the study elucidated the effect of switching from agalsidase alfa to agalsidase beta on immune system as well as other clinical markers. While there was relative decrease in plasma lyso-Gb3 as well as urine lyso-Gb3 over time, their levels remained above the reference values. The immune abnormalities did not correlate with gender, age or lyso-Gb3 levels, indicating that these persistent changes were inherent to FD irrespective of the extent of substrate accumulation.
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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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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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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.