Declining mitochondrial function is an established feature of aging and contributes to most aging-related diseases through its impact on various pathologies such as chronic inflammation, fibrosis and Show more
Declining mitochondrial function is an established feature of aging and contributes to most aging-related diseases through its impact on various pathologies such as chronic inflammation, fibrosis and cellular senescence. Our recent work suggests that benign prostatic hyperplasia, which is an aging-related disease frequently associated with inflammation, fibrosis and senescence, is characterized by a decline in mitochondrial function. Here, we utilize glycolytic restriction and pharmacologic inhibition of the mitochondrial electron transfer chain complex I to promote mitochondrial dysfunction and identify the cellular processes impacted by declining mitochondrial function in benign prostate stromal cells. Using this model, we show that mitochondrial dysfunction induced alterations in cell-cell and cell-matrix adhesion, elevated fibronectin expression, resistance to anoikis and stress-induced premature senescence (SIPS). We also showed that ablation of ZC3H4, a transcription termination factor implicated in anoikis-resistance and reduced in BPH relative to normal prostates, phenocopied various phenotypes in the human BHPrS1 prostate stromal cell line that resulted from inhibition of complex I. Furthermore, ZC3H4 ablation resulted in the elevation of mitochondrial superoxide (mtROS) and mitochondrial membrane potential, altered mitochondrial morphology and NAD Show less
The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant varia Show more
The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows. The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases. Show less