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Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
The clinical hallmarks are palmar xanthomas and tubero-eruptive xanthomas (Figure 11.19) and there is a high risk of premature CAD and peripheral vascular disease. Due to accumulation of remnant particles, both plasma cholesterol and triglyceride are markedly raised. Remnant particles produce a characteristic broad β band on lipoprotein electrophoresis. Apoprotein E2 homozygosity can be demonstrated by electrophoresis of apoproteins or by sequencing the apoprotein E gene.
Atherosclerosis
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The metabolism of lipoproteins is connected with the lipids and the specific polypeptides forming the apoprotein part of these complexes.245,246,377 Chylomicrons are not present in the blood of fasting subjects. LDL and HDL are responsible for the majority of cholesterol transport. LDL carries cholesterol throughout the body and HDL mediates its transport into the liver.425 VLDL are triglyceride-rich particles. The metabolic relationship between the different lipoproteins is shown in Figure 25.561,605 The normal daily intake of fat is about 120 grams containing 0.5 to 1.0 g of cholesterol.247 Exogenous fat is transferred to chylomicrons in the mucosal cells of the gut. Apoprotein exchange occurs between chylomicrons and other circulating lipoproteins; apoC and apoE are transferred as essential steps for subsequent catabolism.
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Tissue factor, or thromboplastin, is a trigger for coagulation. It is thought to be a specific trigger, as opposed to the nonspecific triggers of classic intrinsic coagulation (negatively charged surfaces). Although it is the trigger, the difficulty remains in determining how factor VII is converted to factor VIIa. Tissue factor has no proteolytic activity; thus, just the combination of tissue factor with factor VII is not sufficient to initiate clotting. Tissue factor is a protein–lipid complex that requires both components for its activity. The apoprotein has been purified, sequenced and cloned. Its interactions with both phospholipids and with factor VII have been studied extensively, and the location of tissue factor in cells, atherosclerotic lesions, and on the surface of activated monocytes has been well documented (29,30). Tissue factor is one of the “reconstituted” components of coagulation. The apoprotein, devoid of any lipid constituents, can be reconstituted by combining the apoprotein with lipid, specifically phosphatidyl choline or phosphatidyl choline-phosphatidyl serine vesicles. The result is tissue factor that has full activity.
Prevalence of hypertension and its associated factors among professional drivers: a population-based study
Published in Acta Cardiologica, 2023
Hossein Ebrahimi, Mina Shayestefar, Seyedeh Solmaz Talebi, Janice Christie, Mohammad Hossein Ebrahimi
Blood samples were taken from all participants after 12 h of fasting. The blood samples were sent to a laboratory to perform a CBC diff test, while the serum was employed for FBS, Chol, TG, HDL-C, LDL-C, and Cr tests. The samples were centrifuged within 30–45 min after collection, and the measurements were done on the same day. Plasma glucose was tested using the enzymatic colorimetric method using the kit made by Pars Azmoon Co., Iran. For blood lipid measurements, total cholesterol and triglyceride kits of Pars Azmoon Co. were employed. Triglyceride was measured using the enzymatic colorimetric method via cholesterol esterase, cholesterol oxidase, and glycerol phosphate oxidase. HDL-C was measured after precipitation of lipoprotein containing apoprotein-B via phosphotungstic acid.
Apoprotein E methylation is correlated with immune microenvironment in hepatocellular carcinoma
Published in Acta Oncologica, 2023
Jiao Li, Shan Tian, Qi Liu, Pailan Peng
Abnormal lipid metabolism is implicated in the occurrence and progression of HCC [18,19]. Dysfunction of lipid metabolism in hepatocytes induces aberrant expression of a series of metabolic genes [20–22]. Our team previously reported the clinical and prognostic significance of APOA-1 in HCC, and we deemed that low levels of APOA-1 mRNA might be a reliable molecular of predicting survival in HCC sufferers [23]. APOE protein is a major apoprotein of the chylomicron, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Our study systematically explored the role of APOE mRNA and DNA methylation in HCC, and we found a negative correlation between APOE mRNA expression and DNA methylation. Moreover, we also investigated the correlation between immune activation status and APOE mRNA as well as APOE methylation. Surprisingly, APOE methylation, rather than APOE mRNA was significantly correlated with immune activation status in HCC. IHC assay was conducted to determine the clinical and prognostic values of APOE protein and to verify the associations between APOE expression and PDL1 as well as CTLA4 in HCC. Hence, this is the first research to systematically elucidate the role of APOE both from transcription and protein levels in HCC patients.
Potential alternatives to current cholinesterase inhibitors: an in silico drug repurposing approach
Published in Drug Development and Industrial Pharmacy, 2021
Debanjan Kundu, Vikash Kumar Dubey
We performed a 50 ns simulation of the butyrylcholinesterase apoprotein as well as with the ligands. We had used Donepezil as the positive control and compared our results with the results generated from the novel ligands. The RMSD trajectories generated showed similar trajectories for the apoprotein and the complexes with Brexipiprazole and Pimavanserin. All the three trajectories converged at around 0.22–0.25 nm deviation (Figure 3(A)). RMSD trajectory of Donepezil continuously rose till 40 ns compared to 10 ns for the other systems. Further, it was stable throughout the simulation after 40 ns. The results indicate better stability of the apoprotein in complex with the novel repurposed drugs. The radius of gyration trajectories indicating the overall compactness of the protein in the presence of the ligands showed almost similar overlapping trajectories for all the three complexes, Donepezil, Brexipiprazole and Pimavanserin.