Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Translation of scientific discoveries into meaningful human applications, particularly novel therapies of human diseases, requires development of suitable animal models. Experimental approaches to test new drugs in preclinical phases often necessitated animal models that not only replicate human disease in etiopathogenesis and pathobiology but also biomarkers development and toxicity prediction. ⋯ The challenges in using the currently available animal models for translational research, particularly for developing potentially new drugs for human disease, coupled with the difficulties in toxicity prediction have led some researchers to develop a scoring system for translatability. These aspects and the challenges in selecting an animal model among those that are available to study human disease pathobiology and drug development are the topics covered in this detailed review.
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Randomized Controlled Trial
Heart-brain signaling in patent foramen ovale-related stroke: differential plasma proteomic expression patterns revealed with a 2-pass liquid chromatography-tandem mass spectrometry discovery workflow.
Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the optimal treatment for this multiorgan disease is unclear. ⋯ The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute-phase response, LXR/RXR activation, and coagulation system. In particular, after PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke.
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It has been found that the expression of fatty acid-binding protein 2 messenger RNA is under dietary control. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on weight loss and secondarily in cardiovascular risk factors and serum adipokine after an enriched polyunsaturated fat hypocaloric diet in obese patients. ⋯ Carriers of Thr54 allele have a better metabolic response than obese carriers with Ala54Ala genotype, with a decrease of total cholesterol, low-density lipoprotein cholesterol, insulin levels, leptin levels, and homeostasis model assessment for insulin sensitivity.
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The peroxisome proliferator-activated receptor alpha (PPARA) and apolipoprotein E (APOE) proteins are reported to be correlated with lipid metabolism, cardiovascular disease, and breast cancer. ⋯ These findings suggest that the APOE ε4 genotype plays a major role in the prediction of breast cancer, but the PPARA F24 mutation enhances this outcome. The combined effects of F24/ε4 genotypes are positively associated with risk of breast cancer.
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Gamma-glutamyltransferase (GGT) is a novel cardiovascular disease (CVD) risk factor, but its use as an independent factor for general CVD risk prediction remains unclear in general population. This study examined the association between serum GGT concentration and 10-year CVD risk in Koreans. ⋯ Increased GGT concentration is associated with the increase in 10-year CVD risk. Serum GGT may be helpful to predict the future risk of general CVD.