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In conclusion, phenylalanine, X-12,100 hydroxytryptophan, and 5-hydroxyproline have a causal relationship with the occurrence of PD and may be potential early screening biomarkers and blocking targets

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Glossary ASCVD Atherosclerotic cardiovascular disease AS atherosclerosis CHD coronary heart disease GA Gallic acid T2DM type 2 diabetes HOMA-IR Homeostasis Model Assessment of Insulin Resistance STZ streptozotocin SFRP4 secreted frizzled-related protein 4 IR insulin receptor IRS-1 insulin receptor substrate 1 PI3K Phosphoinositide 3-Kinase Akt Protein Kinase B NF-B Nuclear Factor kappa-light-chain-enhancer of activated B cells IL-6 Interleukin-6 TNF- Tumor Necrosis Factor-alpha GLUT2 glucose transporter 2 SGLT1 sodium-dependent glucose transporter protein 1 ACC acetyl-CoA carboxylase LDL low-density lipoprotein HFD high-fat diet TG triglyceride FAS Fatty Acid Synthase pAMPK phosphorylated AMP-activated protein kinase OA oleic acid NAFLD non-alcoholic fatty liver disease ATGL Adipose triglyceride lipase HSL hormone-sensitive lipase PPAR Peroxisome Proliferator-Activated Receptor Gamma PPAR Peroxisome proliferator-activatedve receptor alpha BAT Brown adipose tissue Fas/FasL Fas Cell Surface Death Receptor/Fas Ligand Fabp4 fatty acid-binding protein-4 L-NAME N-Nitro-L-arginine methyl ester ERK Extracellular Signal-Regulated Kinase CypD Cyclophilin D HDAC1 histone deacetylase 1 HDAC2 histone deacetylase 2 HUVEC human umbilical vein endothelial cells HMEC-1 human microvascular endothelial cells Nox NADPH Oxidase eNOS endothelial nitric oxide synthase LV left ventricle SHRs spontaneously hypertensive rats CaMKII calcium/calmodulin-dependent protein kinase II ISO isoproterenol I/R ischemia/reperfusion ROS Reactive Oxygen Species MDA malondialdehyde MPO myeloperoxidase SOD superoxide dismutase CAT catalase GPx glutathione peroxidase GST purinergic enzymes, detoxifying enzymes -ALA-D heme biosynthesizing enzymes LDH lactate dehydrogenase TBARS Thiobarbituric Acid Reactive Substances LTB4DH Leukotriene B4 12-Hydroxydehydrogenase PTEN Phosphatase and Tensin Homolog deleted on Chromosome 10 RhoA Ras Homolog Family Member A Rac1 Ras-related C3 Botulinum Toxin Substrate 1 CDC42 Cell Division Cycle 42 CDK1 cytokinin-dependent kinase 1 TGF- transforming growth factor- LVDP left ventricular developed pressure dp/dt rates of pressure development RPP rate-pressure product cTnT cardiac troponin T VD vascular dementia 2VO permanent bilateral common carotid artery occlusion CHI cerebral hypoperfusion ischemia MCAO Middle Cerebral Artery Occlusion MPTP mitochondrial permeability transition pore MMPs matrix metalloproteinases BBB blood-brain barrier SDH shikimate dehydrogenase BCCA bilateral common carotid artery GSPE grape seed polyphenol extract Cmax maximum plasma concentration Tmax time to reach maximum concentration T1/2 half-life AUC the area under the curve HPLC High-performance liquid chromatography LPHNs lipid-polymer hybrid nanoparticle system GANPs GA into nanoparticles 4- 4-methyl GA 4-OMePCA 4-methyl protocatechuic acid MNPs Magnesium ferrite nanoparticles CS Hydrogels based on chitosan AMPS 2-acrylamido-2-methylpropane sulfonic acid GACNPs GA-based carbon nanoparticles FA ferulic acid HPCD 2-hydroxypropyl--cyclodextrin SNEDDS self-nanoemulsifying drug delivery system SREBP-2 sterol regulatory element-binding protein 2 HMGCS -hydroxy--methylglutaryl-CoA synthase TAG triglyceride PWV pulse wave velocity VSMCs vascular smooth muscle cells AGEs advanced glycation end products DNMT1 DNA (Cytosine-5)-Methyltransferase 1 PKC Protein Kinase C alpha p38 MAPK p38 Mitogen-Activated Protein Kinase GSK3 Glycogen Synthase Kinase 3 beta CPK creatine phosphokinase CK-MB creatine kinase-MB 4VO four-vessel occlusion

10.1371/journal.pone.0077572 PLoS One 52 MarjaskaM.McCartenJ

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