Lipids play an important role in the pathogenesis of cardiovascular disease. Changes in lipids of erythrocytes are indicative of the outcome of pathophysiological processes. In the present study, we assessed whether the lipid profiles of erythrocytes from heart failure (HF) patients are informative of their disease risk. The lipidomes of erythrocytes from 10 control subjects and 29 patients at different HF stages were analyzed using liquid chromatography time-of-flight mass spectrometry. The lipid composition of erythrocytes obtained from HF patients was significantly different from that of normal controls. The levels of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and sphingomyelins decreased in HF erythrocytes as compared with those of control subjects; however, the levels of lysoPCs, lysoPEs, and ceramides increased in HF erythrocytes. Notably, the oxidized cholesterol 7-ketocholesterol (7KCh) accumulated to higher level in HF erythrocytes than in plasma from the same patients. We further validated our findings with a cohort of 115 subjects of control subjects (n=28) and patients (n=87). Mechanistically, 7KCh promoted reactive oxygen species (ROS) formation in cardiomyocytes; and induced their death, probably through an ATF4-dependent pathway. Our findings suggest that erythrocytic 7KCh can be a risk factor for HF, and is probably implicated in its pathophysiology.

7-Ketocholesterol (7KCh) is a major oxidized cholesterol product abundant in lipoprotein deposits and atherosclerotic plaques. Our previous study has shown that 7KCh accumulates in erythrocytes of heart failure patients, and further investigation centered on how 7KCh may affect metabolism in cardiomyocytes. We applied metabolomics to study the metabolic changes in cardiac cell line HL-1 after treatment with 7KCh. Mevalonic acid (MVA) pathway-derived metabolites, such as farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, phospholipids, and triacylglycerols levels significantly declined, while the levels of lysophospholipids, such as lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs), considerably increased in 7KCh-treated cells. Furthermore, the cholesterol content showed no significant change, but the production of cholesteryl esters was enhanced in the treated cells. To explore the possible mechanisms, we applied mRNA-sequencing (mRNA-seq) to study genes differentially expressed in 7KCh-treated cells. The transcriptomic analysis revealed that genes involved in lipid metabolic processes, including MVA biosynthesis and cholesterol transport and esterification, were differentially expressed in treated cells. Integrated analysis of both metabolomic and transcriptomic data suggests that 7KCh induces cholesteryl ester accumulation and reprogramming of lipid metabolism through altered transcription of such genes as sterol O-acyltransferase- and phospholipase A2-encoding genes. The 7KCh-induced reprogramming of lipid metabolism in cardiac cells may be implicated in the pathogenesis of cardiovascular diseases.

In this study, chicken breast meat was hydrolyzed enzymatically to obtain chicken meat hydrolysate with its molecular weight to a large extent (98%) less than 3000 Da. The hydrolysate was capable of binding bile acids dose-dependently. The potential hypolipidemic effect of this hydrolysate was evaluated in high-fat-fed hamsters. Total free amino acids in the hydrolysate were seven times higher than those in the chicken meat. As compared with high-fat control, the inclusion of hydrolysate resulted in decreased concentrations of serum TG (by 16-34%) and TC (by 6-20%). The animals fed hydrolysate at a high dose exhibited 30% lower serum LDL-C levels and maintained a higher ratio of HDL-C/LDL-C (0.54) than those fed casein (0.36). Moreover, higher levels of hydrolysate inclusion were associated with increased outputs of fecal bile acid and total lipid, suggesting an association between hypocholesterolemic potential and bile acid binding capacity of the chicken hydrolysate.Capacidad del hidrolizado de proteína de pollo para reducir el colesterol sérico mediante su actividad de unión a los ácidos de la bilis RESUMEN En el presente estudio se hidrolizó enzimáticamente carne de pechuga de pollo para obtener hidrolizado de carne de pollo con un peso molecular muy inferior (98%) a 3,000 Da. El hidrolizado pudo unir los ácidos biliares de modo dosis dependiente. Posteriormente, se evaluó el efecto hipolipidémico potencial de este hidrolizado en hámsteres alimentados con mucha grasa. Se verificó que, en el hidrolizado, el total de aminoácidos libres fue siete veces mayor que en la carne de pollo. En comparación con el control de alto contenido graso, la inclusión del hidrolizado dio lugar a una disminución de las concentraciones de TG (en 16-34%) y TC (en 6-20%) en el suero. Además, se constató que los animales alimentados con altas dosis de hidrolizado exhibieron niveles de LDL-C en suero 30% más bajos y mantuvieron una proporción más alta de HDL-C/LDL-C (0.54) que los alimentados con caseína (0.36). Asimismo, la inclusión de niveles más altos de hidrolizado se vinculó con un aumento de la producción de ácido biliar fecal y de lípidos totales, lo que sugiere una asociación entre el potencial hipocolesterolémico y la capacidad de unión de los ácidos biliares del hidrolizado de pollo.

The major oxidized product of cholesterol, 7-Ketocholesterol (7KCh), causes cellular oxidative damage. In the present study, we investigated the physiological responses of cardiomyocytes to 7KCh. A 7KCh treatment inhibited the growth of cardiac cells and their mitochondrial oxygen consumption. It was accompanied by a compensatory increase in mitochondrial mass and adaptive metabolic remodeling. The application of [U-13C] glucose labeling revealed an increased production of malonyl-CoA but a decreased formation of hydroxymethylglutaryl-coenzyme A (HMG-CoA) in the 7KCh-treated cells. The flux of the tricarboxylic acid (TCA) cycle decreased, while that of anaplerotic reaction increased, suggesting a net conversion of pyruvate to malonyl-CoA. The accumulation of malonyl-CoA inhibited the carnitine palmitoyltransferase-1 (CPT-1) activity, probably accounting for the 7-KCh-induced suppression of β-oxidation. We further examined the physiological roles of malonyl-CoA accumulation. Treatment with the inhibitor of malonyl-CoA decarboxylase, which increased the intracellular malonyl-CoA level, mitigated the growth inhibitory effect of 7KCh, whereas the treatment with the inhibitor of acetyl-CoA carboxylase, which reduced malonyl-CoA content, aggravated such a growth inhibitory effect. Knockout of malonyl-CoA decarboxylase gene (Mlycd−/−) alleviated the growth inhibitory effect of 7KCh. It was accompanied by improvement of the mitochondrial functions. These findings suggest that the formation of malonyl-CoA may represent a compensatory cytoprotective mechanism to sustain the growth of 7KCh-treated cells.

Remote screen recording is a system that records whole actions on a remote computer screen, and displays the actions on a client computer screen at the same time. Traditionally, screen recording are streamed in a video format, which large data usually results in high CPU utilization and heavy network loading. Therefore, in order to reduce CPU utilization and network bandwidth loading, the screen recording system records and only sends the blocks which have updates on the recording screen. A screen update on any part of the recording screen is called a "changed block" in this paper. Only recording and sending the changed blocks definitely reduces the network bandwidth and CPU loading. Because of only sending changed blocks, this study comes up with a media synchronization problem between a video stream and remote screen data stream in a distance learning system due to an unstable network environment. This study proposes a fast skip mechanism, called Fast Media Synchronization (FMS), to match the video stream playback by adjusting the remote screen data stream. The FMS quickly determines whether the changed blocks overlap. In the fast skip mechanism of FMS, overlapping areas among changed blocks in a screen data stream will be effectively deleted. In this paper, four different scenarios web browsing, document editing, slide presentation, and video playback, are designed to test the effectiveness of applying FMS. The experiment results shows that the FMS mechanism approximately reduces 85% of processing time, 57% to 99% of the frequency of pasting times, 70% to 90% the number of comparisons, and 70% to 90% the total pasting area. Furthermore, the proposed FMS mechanism can also be applied to improve the efficiency of different screen recording systems, such as remote desktop, distance conferencing, and video streaming, etc.