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.