You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: ["HealthCareActivity", "InjuryOrPoisoning", "BodySubstance", "IntellectualProduct", "AnatomicalStructure", "SpatialConcept", "Chemical", "Bacterium", "MedicalDevice", "Organization", "BiomedicalOccupationOrDiscipline", "Finding", "BiologicFunction", "Virus", "ResearchActivity", "ClinicalAttribute", "PopulationGroup", "Eukaryote", "BodySystem", "Food", "ProfessionalOrOccupationalGroup"].

Please return the output as a JSON object of the format: {"Virus": ["HIV", ...], "Bacterium": ["MRSA", ...], "AnatomicalStructure": ["Lung", ...], "BodySystem": ["CNS", ...], "BodySubstance": ["Serum", ...], "Finding": ["Headache", ...], "InjuryOrPoisoning": ["Fracture", ...], "BiologicFunction": ["Death", ...], "HealthCareActivity": ["Biopsy", ...], "ResearchActivity": ["Clinical trial", ...], "MedicalDevice": ["Lenses", ...], "SpatialConcept": ["Camps", ...], "BiomedicalOccupationOrDiscipline": ["Forensic medicine", ...], "Organization": ["WHO", ...], "ProfessionalOrOccupationalGroup": ["Provider", ...], "PopulationGroup": ["Swimmers", ...], "Chemical": ["Gold", ...], "Food": ["Rice", ...], "IntellectualProduct": ["RPAM", ...], "ClinicalAttribute": ["Biomarker", ...], "Eukaryote": ["Dogs", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].

Only output the JSON object and do not include any additional text.

Abstract:

Attenuation of High Glucose - Induced Rat Cardiomyocyte Apoptosis by Exendin-4 via Intervention of HO-1 / Nrf-2 and the PI3K/AKT Signaling Pathway Exendin-4, a glucagon-like peptide-1 receptor agonist, demonstrated cytoprotective actions beyond glycemic control in recent studies. The aims of the present study were to investigate the effects of exendin-4 on high glucose (HG)- induced cardiomyocyte apoptosis and the possible mechanisms. Rat cardiomyocytes were divided into 3 groups: normal glucose group (NG group), HG group and HG + exendin-4 group (HG + Ex Group). Cardiomyocyte apoptosis was evaluated by double-staining with annexin V-fluorescein isothiocyanate (FITC)/ propidium iodide (PI) and flow cytometry. Intracellular reactive oxygen species (ROS) production was detected by 2’,7’-dichlorodihydrofluorescein diacetate (DCHF-DA) incubation and fluorescence microscopy. LY294002 (LY), a phosphoinositide 3-kinase (PI3K) pathway inhibitor, was added to the medium of the HG + Ex + LY Group for further western blot analysis. The proteins analyzed involved oxidative stress - associated proteins, heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf-2), and apoptosis - associated proteins, caspase-3, Bax/B-cell lymphoma 2 (Bcl-2) and p-AKT / AKT. HG treatment induced cardiomyocyte apoptosis (P = 0.00) and clearly upregulated ROS production (P = 0.00); exendin-4 co-incubation also ameliorated cardiomyocyte apoptosis (P = 0.004) and decreased ROS (P = 0.00) level significantly. HO-1 and Nrf-2 protein expression levels decreased significantly in the HG group (P < 0.05), but the levels were elevated by exendin-4 intervention (P < 0.05). Furthermore, exendin-4 attenuated HG - induced higher protein expression, including cleaved caspase-3 and Bax, increased the expression of Bcl-2 protein (P < 0.05). However, these impacts of exendin-4 were counteracted significantly by co-incubation with LY294002. In addition, exendin-4 ameliorated HG - induced p-AKT / AKT lower expression, and this impact was also suppressed by LY294002. Exendin-4 ameliorates HG - induced cardiomyocyte apoptosis, and the mechanisms may involve anti-oxidative stress via the HO-1 / Nrf-2 system, as well as intervention of the PI3K/AKT signaling pathway.
{"AnatomicalStructure": ["cardiomyocyte", "Cardiomyocyte", "cardiomyocytes"], "Bacterium": [], "BiologicFunction": ["apoptosis", "pathway", "Apoptosis", "upregulated", "expression", "lower expression", "anti-oxidative stress", "cytoprotective actions", "protein expression", "oxidative stress"], "BiomedicalOccupationOrDiscipline": [], "BodySubstance": [], "BodySystem": [], "Chemical": ["heme oxygenase-1", "caspase-3", "medium", "p-AKT", "nuclear factor E2-related factor 2", "AKT", "FITC", "HG", "Bcl-2", "Bcl-2 protein", "DCHF-DA", "Nrf-2", "associated proteins", "glucagon-like peptide-1 receptor agonist", "HO-1", "NG", "Ex", "High Glucose", "exendin-4", "Exendin-4", "2\u2019,7\u2019-dichlorodihydrofluorescein diacetate", "ROS", "LY294002", "PI3K", "LY", "proteins", "Bax", "high glucose", "propidium iodide", "Bax/B-cell lymphoma 2", "normal glucose", "PI", "phosphoinositide 3-kinase", "annexin V-fluorescein isothiocyanate"], "ClinicalAttribute": [], "Eukaryote": ["Rat"], "Finding": ["glycemic control", "detected"], "Food": [], "HealthCareActivity": ["double-staining", "co-incubation", "fluorescence microscopy", "incubation", "intervention", "Intervention", "flow cytometry", "western blot analysis"], "InjuryOrPoisoning": [], "IntellectualProduct": [], "MedicalDevice": [], "Organization": [], "PopulationGroup": [], "ProfessionalOrOccupationalGroup": [], "ResearchActivity": ["analyzed", "study"], "SpatialConcept": ["Intracellular"], "Virus": []}