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Cerebral ischemia is an extremely complex disease that can be caused by a variety of factors. Cerebral ischemia can cause great harm to human body. Sevoflurane is a volatile anesthetic that is frequently used in clinic, and has a lot of advantages, such as quick induction of general anesthesia, quick anesthesia recovery, no respiratory tract irritation, muscle relaxation, and small cycle effect. The mechanism of sevoflurane preconditioning or post-treatment induction is poorly understood. The purpose of this study was to illustrate the mechanism underlying sevoflurane-induced protection in cerebral ischemia–reperfusion injury and also provide theoretical guidance for future research.

We extracted Sal B and TIIA from Salvia miltiorrhiza using enzymatic-assisted ethanol extraction. ACONN predicted optimal process conditions. Enzymolysis and alcohol extraction were used, optimizing conditions and evaluating antioxidant activity. ACONN analyzed data and ACO optimized conditions. Lab verification comprehensively evaluated the conditions. The correlation between Sal B, TIIA, and their antioxidant activities was examined. Weights of 0.5739 and 0.4260 evaluated Sal B and TIIA. ACONN had a 97.46% fitting degree. Optimized extraction conditions improved yield and quality, yielding a comprehensive evaluation value of 27.69 with 4.46% average errors. This approach enhances extraction and compound quality. Antioxidant activity strongly correlated with component yield, influenced by extraction conditions. ACONN-optimized extraction improved Sal B and TIIA yield and quality, with potential as natural antioxidants. Integrating machine learning and optimization algorithms in industrial extraction enhances efficiency and environmental preservation. [ABSTRACT FROM AUTHOR]

Background: Considering the strong correlation made between Alzheimer's disease (AD) and the pathology of glucose metabolism disorder, we sought to analyze the effects of fasting blood glucose (FBG) level, fasting plasma insulin (FINS) level, and insulin resistance index (HOMA-IR) on the risk and severity of AD.Objective: Reveal the pathological relationship between AD and insulin resistance.Methods: We searched 5 databases from inception through April 4, 2022. Meta-regression was conducted to identify if there were significant differences between groups. Shapiro-Wilk test and the Q-Q diagram were applied to evaluate the normality of variables. A multiple logistic regression model was employed to explore the association between FBG, FINS, HOMA-IR, and Mini-Mental State Examination scale score (MMSE).Results: 47 qualified articles including 2,981 patients were enrolled in our study. FBG (p < 0.001), FINS (p < 0.001), and HOMA-IR (p < 0.001) were higher in AD patients than in controls. HOMA-IR was negatively correlated with MMSE (p = 0.001) and positively related to the sex ratio (male versus female) (p < 0.05). HOMA-IR obeyed lognormal distribution (p > 0.05), and the 95% bilateral boundary values were 0.73 and 10.67. FBG (p = 0.479) was positively correlated to MMSE, while FINS (p = 0.1657) was negatively correlated with MMSE.Conclusion: The increase in the levels of FBG, FINS, and HOMA-IR served as precise indicators of the risk of AD. HOMA-IR was found to be correlated to the increasing severity of AD, especially in male AD patients. [ABSTRACT FROM AUTHOR]

Accumulation of cholesteryl esters (CEs) in macrophage foam cells, central to atherosclerotic plaque formation, occurs as a result of imbalance between the cholesterol influx and efflux pathways. While the uptake, [...]

Reduction of the lipid burden of atherosclerotic lesion-associated macrophage foam cells is a logical strategy to reduce the plaque volume. Since extracellular cholesterol acceptor-mediated cholesterol efflux is the only recognized mechanism of cholesterol removal from foam cells and this process is rate limited at the level of intracellular cholesterol ester hydrolysis, a reaction catalyzed by neutral cholesteryl ester hydrolase (CEH), we examined the hypothesis that CEH overexpression in the human macrophage monocyte/macrophage cell line THP1 results in increased cholesterol efflux, as well as decreased cellular cholesterol ester accumulation. We generated THP1-CEH cells with stable integration of human macrophage CEH cDNA driven by the cytomegalovirus promoter. Compared with wild-type THP1 cells (THP1-WT), THP1-CEH cells showed increased CEH mRNA expression and increased CEH activity. Efflux of free or unesterified cholesterol by acetylated LDL-loaded THP1-CEH cells to ApoA-I by an ABCA1-dependent pathway or to HDL by an ABCG1-dependent pathway was significantly higher than that in THP1-WT cells. In addition, THP1-CEH cells accumulated significantly lower amount of esterified cholesterol. CEH overexpression, therefore, not only enhances cholesterol efflux but also reduces cellular accumulation of cholesteryl esters. Taken together, these data provide evidence for evaluating CEH expression in human macrophages as a potential target for attenuation of foam cell formation and regression of atherosclerotic plaques. lipoproteins; lipid burden; foam cells

Cellular cholesterol balance induces changes in the inflammatory status of macrophages, and low grade chronic inflammation is increasingly being recognized as one of the key steps in the development of atherosclerosis as well as insulin resistance. Cholesteryl ester hydrolase (CEH) catalyzes the hydrolysis of intracellular stored cholesteryl esters (CEs) and thereby enhances free cholesterol efflux and reduces cellular CE content. We have earlier reported reduced atherosclerosis and lesion necrosis in macrophage-specific CEH transgenic mice on a Ldlr-/- background. In the present study, we tested the hypothesis that reduced intracellular accumulation of CE in macrophages from CEH transgenic mice will attenuate expression of proinflammatory mediators, thereby reducing infiltration into adipose tissue, alleviating inflammation, and resulting in improved insulin sensitivity. Western diet fed Ld1rCEH transgenic mice showed improved insulin sensitivity as assessed by glucose and insulin tolerance tests. Macrophages from CEH transgenic mice expressed significantly lower levels of proinflammatory cytokines (interleukin-113 and interleukin-6) and chemokine (MCP1; monocyte chemoattractant protein). Attenuation of NP-KBand AP-1-driven gene expression was determined to be the underlying mechanism. Infiltration of macrophages into the adipose tissue that increases inflammation and impairs insulin signaling was also significantly reduced in Ldlr CEH transgenic mice. In the OP-9 adipocyte peritoneal macrophage co-culture system, macrophages from CEH transgenic mice had a significantly reduced effect on insulin signaling as measured by Akt phosphorylation compared with nontransgenic macrophages. Taken together, these studies demonstrate that macrophage-specific overexpression of CEH decreases expression of proinflammatory mediators and attenuates macrophage infiltration into the adipose tissue, resulting in decreased circulating cytokines and improved insulin sensitivity. [ABSTRACT FROM AUTHOR]

Background: End-stage renal disease patients have significant cardiovascular morbidity and mortality, but little is known about differences in coagulation profiles between patients on hemodialysis (HD) and on peritoneal dialysis (PD). Given their long-term exposure to glucose-based dialysate, patients on PD can experience metabolic derangements. Theoretically, that exposure should create a more prothrombotic environment than occurs in HD patients. The objective of the present study was to quantify potential differences in baseline coagulation between PD and HD patients. ♢, Methods: Our single-center cross-sectional study at a large academic health science center enrolled 50 age-, race-, and sex-matched subjects (10 control subjects, 20 HD patients, and 20 PD patients). Measurements included platelet function, platelet receptor distribution, and coagulation dynamics by thromboelastography and Hemodyne hemostasis assay (Hemodyne, Richmond, VA, USA). ♢, Results: Compared with healthy control subjects, patients on both forms of dialysis showed prothrombotic coagulation protein profiles. The tissue-factor pathway was markedly elevated in both groups, but PD was associated with significantly greater concentrations of tissue factor (p = 0.0056) and tissue-factor pathway inhibitor (p = 0.0138). Similarly, compared with patients receiving HD, patients on PD had greater concentrations of fibrinogen (p = 0.0325), which corresponded with platelet hyperfunction as measured by platelet contractile force and clot elastic modulus (p = 0.003 and 0.017 respectively, compared with values in HD patients). Platelet receptor distribution was similar between the groups. ♢, Conclusions: Compared with patients on HD, patients on PD appear to have a more prothrombotic profile. The clinical relevance of these findings needs to be studied in a prospective manner.