The Effect of Fermented Lingonberry Juice onCandida glabrataIntracellular Protein Expression

Lingonberries have a long traditional use in treating fungal infections on mucosal membranes, but very little is known about the exact antifungal mechanisms. We tested the effects of fermented lingonberry juice onCandida glabrataintracellular protein expression. ACandida glabrataclinical strain was grown in the presence of fermented lingonberry juice (FLJ). Also the effect of lowered pH was tested. Intracellular protein expression levels were analyzed by the 2D-DIGE method. Six proteins detected with ≥1.5-fold lowered expression levels from FLJ treated cells were further characterized with LC-MS/MS. Heat shock protein 9/12 and redoxin were identified with peptide coverage/scores of 68/129 and 21/26, respectively. Heat shock protein 9/12 had an oxidized methionine at position 56. We found no differences in protein expression levels at pH 3.5 compared to pH 7.6. These results demonstrate that FLJ exerts an intracellular stress response inCandida glabrata, plausibly impairing its ability to express proteins related to oxidative stress or maintaining cell wall integrity.

Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction

Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis.