3-bromopyruvate cholesterol ester enhances the sensitivity of breast cancer cells to tamoxifen / 中国临床药理学与治疗学

AIM: To investigate the effect of 3-bro-mopyruvate cholesterol ester (3-BP-Cl) on the sensitivity of breast cancer to tamoxifen (TAM). METHODS: MTT assay and Calcein AM/PI staining were used to detect the effect of drugs on the viability of breast cancer cells. Kim's formula was used to detect synergistic anti-breast cancer effect of cholesterol 3-bromopyruvate and tamoxifen. The inhibitory effect of drugs on proliferation of breast cancer cells was detected by colony-forming assay. Flow cytometry was used to detect the apoptosis of breast cancer cells. Western blot assay was used to detect the expression of hexokinase 2, Bcl-2 and Bax proteins. RESULTS: MTT results showed that combination 3-BP-Cl and TAM could significantly inhibit the activity of MCF-7 cells (P1.15). Calcein AM / PI staining showed that the number of dead cells was the highest in the combination group. Colony-forming assay showed that the combination group had stronger inhibitory effect on the proliferation of MCF-7 cells than that of single drug groups. AnnexinV flow cytometry results showed that, the cell apoptosis in the combination group was significantly increased (P<0.01). Western blot results showed that 3-BP-Cl inhibited the expressions of hexoktokinase 2 and Bcl-2, and enhanced the expression of Bax in MCF-7 cells. CONCLUSION: 3-BP-Cl could increase the sensitivity of breast cancer cells to tamoxifen, and synergically inhibit the proliferation of breast cancer cells. The mechanism is possibly related to its effects of inhibiting the expression of HK2/Bcl-2, and enhancing the expression of Bax.

A STUDY TO EVALUATE THE IMPORTANCE OF FASTING LIPID PROFILE ESTIMATION AS THE PART OF INITIAL EVALUATION OF HIV POSITIVE PATIENTS BEFORE STARTING HAART

BACKGROUND:-There is evidence that ART is associated with lipodystrophy syndrome, a disturbance of lipid metabolism characterised by insulin resistance, dyslipidaemia, and fat maldistribution, metabolic bone disease (osteopenia and/or osteoporosis), and lactic acidosis. ART- associated dyslipidaemia is characterized by elevated serum concentrations of total cholesterol, triglycerides, low density lipoprotein 2(LDL-c), very low-density lipoprotein (VLDL), and Apo lipoprotein B (apoB) and low levels of high density lipoprotein (HDL-c) constituting an atherogenic lipid 1pro?le . In this study 143 young patients who were attending the Antiretroviral Therapy Plus MATERIAL AND METHODS:- Centre & Medicine Wards, ACSR GMC NELLORE were included randomly. 5ml Sample preparation and Biochemical assay :- of venous blood sample was collected by venipuncture from 12 hours overnight fast and centrifuged at 3000 cycles per minute and serum was separated for lipid pro?le measurement within one hour of blood collection. The serum levels of TC, HDL-C, LDL-C, VLDL and TG were measured using AU480 BECKMANS random access fully automated auto analyzer at Biochemistry laboratory, ACSR GMC, NELLORE. TC, LDL and TC/HDL lipid pro?les are signi?cant. F-Signi?cant values are RESULTS;- <0.05, reject null hypothesis. It means that the difference among the lipid pro?les of TC, LDL and TC/HDL in the study group is statistically signi?cant with respect to regimen groups. HDL, TG and VLDL lipid pro?les are not signi?cant. F-Signi?cant values are >0.05, no evidence to reject null hypothesis. It means that the no signi?cant difference among the lipid pro?les of HDL, TG, and VLDL in the study group is not statistically signi?cant with respect to regimen groups. Signi?cant CONCLUSIONS:- metabolic and morphological alterations occur in HIV infected patients especially in patients on HAART. The patients on HAART had an elevated Castelli Index I, indicating an increased risk for atherosclerotic cardiovascular disease in this population. There is need to assess lipid pro?les at baseline before initiation of HAART treatment and lipid pro?le monitoring during therapy to monitor any rising trends. New medications with more lipid friendly pro?les within existing drugs such as darunavir (PI), etravirine (NNRTI), new classes of drugs such as integrase inhibitors (raltegravir) and CCR5 inhibitors (maraviroc) can be used to avoid dyslipidaemia

Gene polymorphisms of cytochrome B-245 alpha chain (CYBA) and cholesteryl ester transfer protein (CETP) and susceptibility to generalized aggressive periodontitis / 北京大学学报(医学版)

OBJECTIVE@#To explore the correlation of cytochrome B-245 alpha chain (CYBA) rs4673 and cholesteryl ester transfer protein (CETP) rs12720922 polymorphisms with the susceptibility of gene-ralized aggressive periodontitis (GAgP).@*METHODS@#The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The CYBA rs4673 and CETP rs12720922 polymorphisms were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Logistic regression models were used to analyze the correlation of CYBA rs4673 and CETP rs12720922 variants with the susceptibility of GAgP. The interaction between the two gene polymorphisms to the susceptibility of GAgP was analyzed by the likelihood ratio test. The interaction model adopted was the multiplication model.@*RESULTS@#The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups (P < 0.05). The gender distribution (male/female) was 152/220 and 53/80 respectively, and there was no significant difference between GAgP group and controls (P>0.05). For CYBA rs4673, the frequency of CT/TT genotype in the GAgP group was significantly higher than that in the controls [18.0% (66/366) vs. 10.6% (14/132), P < 0.05]. After adjusting age and gender, the individuals with CT/TT genotype had a higher risk of GAgP (OR=1.86, 95%CI: 1.01-3.45, P < 0.05), compared with CC genotype. There was no statistically significant difference in distributions of the CETP rs12720922 genotypes (GG, AA/AG) between GAgP patients and healthy controls (P>0.05). A significant interaction between CYBA rs4673 and CETP rs12720922 in the susceptibility to GAgP was observed. The GAgP risk of the individuals with CYBA rs4673 CT/TT and CETP rs12720922 GG genotypes was significantly increased (OR=3.25, 95%CI: 1.36-7.75, P < 0.01), compared with those carrying CC and AA/AG genotypes.@*CONCLUSION@#CYBA rs4673 CT/TT genotype is associated with GAgP susceptibility. There is a significant interaction between CYBA rs4673 CT/TT genotype and CETP rs12720922 GG genotype in the susceptibility of GAgP.

Expression and biological role of the neutral cholesterol ester hydrolase 1 gene in liver cancer tissue and cell lines / 临床肝胆病杂志

ObjectiveTo investigate the expression of the neutral cholesterol ester hydrolase 1 (NCEH1) gene in liver cancer tissue and human hepatoma cell lines and the effect of NCEH1 gene knockdown on the proliferation, apoptosis, invasion, and metastasis abilities of human hepatoma SMMC-7721 cells. MethodsLiver cancer tissue samples and adjacent tissue samples were collected from 32 patients with liver cancer who underwent surgical treatment in Guangzhou Red Cross Hospital Affiliated to Jinan University from January 2013 to June 2019, and quantitative real-time PCR was used to measure the relative expression level of the NCEH1 gene. Gene expression data of liver cancer samples up to September 2020 were downloaded from the ICGC database, and R software was used to analyze the data and obtain the expression level of the NCEH1 gene in each sample. The paired Wilcoxon signed-rank test and the Wilcoxon rank-sum test were used to investigate the differences between liver cancer tissue and adjacent tissue. Quantitative real-time PCR was used to measure the expression level of the NCEH1 gene in human hepatoma SMMC-7721, Bel-7402, HepG2, and Hep3B cells and normal human HL7702 liver cells. The lentivirus-mediated small interfering RNA (siRNA) technique was used to establish a human hepatoma SMMC-7721 cell line with NCEH1 gene knockdown, and the cells were divided into NCEH1 knockdown group (KD group) and negative control group (NC group); quantitative real-time PCR was used to measure the knockdown efficiency of the NCEH1 gene, and then MTT assay, flow cytometry with Annexin V-APC single staining, wound healing assay, Transwell assay, and Transwell chamber invasion assay were used to measure the proliferation, apoptosis, metastasis, and invasion abilities of SMMC-7721 cells in both groups. The t-test was used for statistical analysis of data between the two groups. ResultsThe mean expression level of the NCEH1 gene in liver cancer tissue was significantly higher than that in adjacent tissue (specimens from our hospital: Z=2.263, P=0.024; ICGC database: U=18 768, P＜0.001). SMMC-7721 cell line with moderate potential of invasion and metastasis had the highest expression level of the NCEH1 gene, followed by BEL-7402 and HepG2 cell lines with low potential of invasion and metastasis, and Hep3B cell line without the potential of invasion and metastasis had the lowest expression level. The KD group had a significantly lower expression level of the NCEH1 gene than the NC group (t=11.578, P=0000 3), and the knockdown efficiency of the NCEH1 gene was as high as 74.0%. Compared with the NC group, the KD group had a significant reduction in cell growth rate, a significant increase in apoptosis rate, and significant reductions in migration rate and the number of metastatic and invasive cells (t=32.100, 27.303, 9.51, 38.123, and 22.331, all P＜0.001). Conclusion There is a significant increase in the expression of the NCEH1 gene in liver cancer tissue and cell lines, and the NCEH1 gene can promote the growth, proliferation, invasion, and metastasis of hepatoma cells and inhibit their apoptosis, suggesting that it may be a potential therapeutic target for liver cancer.

Serum lipids and lipoproteins: a brief review of the composition, transport and physiological functions

The dietary fats are composed primarily of triacylglycerols and some amount of phospholipids and cholesterol. Being hydrophobic in nature, these are insoluble in water, and hence cannot be transported in the blood plasma per se; to enable these lipids to be transported by the blood stream to various peripheral tissues, nature has devised the technique of making these soluble by binding them to proteins. These proteins involved in lipid transport are known as apolipoproteins, and the protein-lipid particle is known as lipoprotein. Thus, lipoproteins can be considered to be the primary transportmechanism to carry lipids from the alimentary tract to various parts of the body. Lipoproteins have gained prominence in medical field over the past few decades because of their role in the aetio-pathogenesis of cardiovascular diseases, principally atherosclerosis which is the cause of coronary artery disease and myocardial infarction. The various types and sub-types of lipoproteins have been found to have differing and even opposing roles in the development of arterial diseases. An understanding of the differing populations of lipoproteins, the associated proteins and other enzymes, and the myriad variety of inter-actions among themselves and with body cells is vital to our understanding the pathways involved in the development of cardio-vascular disordersand in determining the precise steps where pharmacological interventions can be introduced

Effects of Obesity and Family History of Diabetes on the Association of CETP rs6499861 with HDL-C Level in Korean Populations

OBJECTIVES: The aim of this study was to examine the associations of cholesterol ester transfer protein (CETP) rs6499861 and rs12708980 with high-density lipoprotein cholesterol (HDL-C) considering obesity and family history of diabetes (FHD) in Korean men and women. METHODS: We analyzed the association of CETP single nucleotide polymorphisms (SNPs) with HDL-C among individuals selected from a hospital (n=4 294) and the Bundang-gu area in Korea (n=2 304). RESULTS: We found that the CETP SNP rs6499861 was associated with a lower HDL-C level (effect per allele: −2.044 mg/dL, p<0.0001). Individuals with a rs6499861 CG/GG genotype had a 1.45-fold higher risk of an abnormal level of HDL-C (<40 mg/dL) than those with a CC genotype. This genotype-HDL-C association was stronger in women (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.39–2.85) compared with men (OR, 1.33; 95% CI, 1.10–1.61) and in women with a FHD (OR, 4.82; 95% CI, 1.86–12.5; p=0.0012) compared with women without a family history. Relative to individuals with a CC genotype and body mass index (BMI) <25.69 kg/m², individuals with a CG/GG genotype and BMI ≥25.69 kg/m² had an OR (95% CI) of 2.61 (1.97–3.47). CONCLUSIONS: These findings indicate that CETP variants are linked to HDL-C level in Koreans and that this link is stronger in obese men and in women who have a FHD.

Vaccine strategies in prevention and treatment of atherosclerosis / 上海交通大学学报（医学版）

Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and exogenous antigens. Both proatherogenic as well as atheroprotective roles have been identified for the immune system in atherosclerosis. Hence, it is conceivable that an immuno-modulatory strategy via active immunization against many of these antigens could potentially alter the natural history of atherosclerosis. Cholesterol ester transfer protein (CETP) plays an important role in lipid metabolism, suggesting it might prevent atherosclerosis. This review discusses the recent advances of vaccine targeting the development of atherosclerosis, mainly about the CETP targeting vaccines.

Vaccine strategies in prevention and treatment of atherosclerosis / 上海交通大学学报（医学版）

Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall,with both the innate and adaptive immune systems responding to many endogenous and exogenous antigens.Both proatherogenic as well as atheroprotective roles have been identified for the immune system in atherosclerosis.Hence,it is conceivable that an immuno-modulatory strategy via active immunization against many of these antigens could potentially alter the natural history of atherosclerosis.Cholesterol ester transfer protein (CETP) plays an important role in lipid metabolism,suggesting it might prevent atherosclerosis.This review discusses the recent advances of vaccine targeting the development of atherosclerosis,mainly about the CETP targeting vaccines.

What Do We Get from Recent Statin and CETP Inhibitors Trials?

Recent clinical trials and meta-analyses have indicated that high-intensive statin treatment lowers low-density lipoprotein cholesterol (LDL-C) levels and reduces the risk of nonfatal cardiovascular (CV) events compared with moderate-intensity statin treatment. However, there are residual risks of CV events and safety concerns associated with high-intensity statin treatment. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study showed that ezetimibe plus moderate-intensity statin therapy after acute coronary syndromes incrementally lowers LDL-C levels and improved CV outcomes compared with moderate-intensity statin therapy. However, despite the LDL-C-lowering effects, a substantial residual CV risk still remains, which includes other lipid abnormalities such as low high-density lipoprotein cholesterol (HDL-C). The most representative agents that primarily increase HDL-C are cholesteryl ester transfer protein (CETP) inhibitors. Until now, 4 CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, and anacetrapib, have been introduced and all have significantly raised the HDL-C from 30% to 133%. However, the results for CV outcomes in clinical trials differed, based on the 4 agents. Torcetrapib increased the risk of CV events and total mortality in patients at high CV risk (ILLUMINATE trial). Dalcetrapib and evacetrapib did not result in lower rate of CV events in patients with recent acute coronary syndrome and high risk vascular disease, respectively (dal-OUTCOMES and ACCELERATE trials). However, anacetrapib significantly decreased the incidence of major coronary events in patients with atherosclerotic vascular disease (REVEAL trial). This topic summarizes the major results of recent statin and CETP inhibitor trials and provides framework to interpret and implement the trial results in real clinical practice.

Detección de la mutación E8SJM en el gen LIPA, por PCR en tiempo real, para la investigación de la enfermedad por almacenamiento de ésteres de colesterol / Detection of the E8SJM mutation in the LIPA gene, by real-time PCR, for the investigation of cholesteryl ester storage disease

Introducción: La enfermedad por Almacenamiento de Ésteres de Colesterol (CESD; Cholesteryl Ester Storage Disease) es una enfermedad de depósito lisosomal, su presentación es bastante variable y su diagnóstico constituye un desafío. Además, existe un número de anomalías observadas en los pacientes con CESD que se sobreponen a diagnósticos más comunes, siendo probable que sea subdiagnosticada. La mayoría de pacientes relatados hasta el momento son portadores de la mutación E8SJM en el gen LIPA. En este sentido, el auxilio en el diagnóstico es fundamental pues existen opciones de terapia en desarrollo. Diseño: Estudio observacional. Objetivo: Estandarizar la técnica de PCR en tiempo real para la detección de la mutación más frecuente, E8SJM, en muestras de sangre periférica y de biopsia hepática para el auxilio diagnóstico de CESD y futuros estudios de prevalencia de la mutación. Institución: Centro de Terapia Génica del Hospital de Clínicas de Porto Alegre (HCPA), Brasil. Material biológico: Muestras de ADN extraídas de sangre periférica y tejido hepático parafinado. Principales medidas de resultados: Presencia/Ausencia de la mutación E8SJM. Resultados: Se estandarizó la reacción de PCR en tiempo real, la mutación fue detectada correctamente y posteriormente validada por secuenciación de Sanger. La mutación fue analizada en 137 muestras y encontrada en apenas una paciente que ingresó al Servicio de Genética Médica del HCPA con diagnóstico clínico y bioquímico de CESD/Wolman. Conclusiones: La técnica de PCR en tiempo real es ideal para la detección rápida y en gran escala de la mutación frecuente asociada a CESD.

Introduction: Cholesteryl Ester Storage Disease (CESD) is a lysosomal storage disorder, its presentation is highly variable and its diagnosis challenging. In addition, there are several abnormalities observed in patients with CESD who overlap with more common diagnoses and are likely to be underdiagnosed. Most patients reported to date are carriers of the E8SJM mutation in the LIPA gene. In this sense, diagnostic assistance is essential because there are options for therapy in development, as well as mutation prevalence studies. Design: Observational research. Objective: To standardize the real-time PCR technique for the detection of the most frequent mutation, E8SJM, in peripheral blood and liver biopsy specimens for the diagnosis of CESD and future mutation prevalence studies. Institution: Center of Gene Therapy of the Hospital de Clinicas de Porto Alegre (HCPA), Brazil. Biological material: DNA samples extracted from peripheral blood and paraffinembedded liver tissue. Main outcome measures: Presence / Absence of E8SJM mutation. Results: The PCR reaction was standardized in real time; the mutation was correctly detected and validated by Sanger sequencing. The mutation was analyzed in 137 samples and found in only one patient who entered the Medical Genetics Service of the HCPA with clinical and biochemical diagnosis of CESD/Wolman. Conclusions: The real-time PCR technique is ideal for rapid and large-scale detection of the frequent CESD-associated mutation.

Guía colombiana para el diagnóstico de la deficiencia de lipasa ácida / Colombian Guidelines for Diagnosis of Lipase Acid Deficiency

Resumen Introducción: la deficiencia de lipasa ácida lisosomal (LAL-D) es una entidad de herencia autosómica recesiva que lleva a la acumulación de esteres de colesterol y triglicéridos en el hígado, bazo y otros órganos. La edad de inicio y la tasa de progresión son muy variables, lo que posiblemente sea explicado por las mutaciones presentes en el gen LIPA. Las manifestaciones clínicas son las mismas que para otras patologías hepáticas, cardiovasculares y metabólicas, lo que hace difícil reconocerla en la práctica clínica. Objetivo: proveer una guía que permita a los clínicos reconocer los principales grupos de riesgo en los cuales se debe sospechar de LAL-D y mejorar su diagnóstico. Metodología: este documento se diseñó como un consenso de expertos en el cual participaron médicos especialistas en gastroenterología, hepatología, endocrinología, genética, patología y pediatría. Se realizó una revisión de la literatura acerca de las manifestaciones clínicas y de las herramientas para el diagnóstico de LAL-D y se siguió la metodología de técnica de grupo nominal. Resultados: se generaron algoritmos diagnósticos por consenso para cada uno de los grupos de riesgo, que facilitaran la sospecha y el diagnóstico de LAL-D. Conclusiones: esta guía propone algoritmos para el diagnóstico de LAL-D con base en el consenso clínico, que buscan optimizar la ruta diagnóstica en los pacientes con dicha patología.

Abstract Introduction: Lysosomal acid lipase deficiency (LAL-D) is an inherited autosomal recessive entity that leads to the accumulation of cholesterol and triglyceride esters in the liver, spleen and other organs. The age of onset and rate of progression vary greatly, possibly explained by mutations of the LIPA gene. Clinical manifestations are the same as those of other hepatic, cardiovascular and metabolic pathologies which makes it difficult to recognize in clinical practice. Objective: The objectives of these guidelines is to help clinicians recognize the major groups at risk for LAL-D and to improve its diagnosis. Methodology: This document was designed as a consensus of experts in gastroenterology, hepatology, endocrinology, genetics, pathology and pediatrics. A review of the literature regarding clinical manifestations and tools for diagnosis of LAL-D was conducted and the nominal group technique was followed. Results: Diagnostic algorithms which facilitate suspicion and diagnosis of LAL-D were generated by consensus for each of the risk groups. Conclusions: This guide proposes algorithms for the diagnosis of LAL-D based on clinical consensus. The algorithms seek to optimize diagnosis for patients with this pathology.

Effect of fisetin on proteome of foam cells / 中草药

Objective: To investigate the effect of fisetin (FIS) on foam cells by two-dimensional electrophoresis and mass spectrometry technology, and analyze the molecular mechanism of its inhibition. Methods: MTT method was used to detect the effect of ox-LDL on viability of RAW264.7 cells and fisetin on foam cells separately as well as chemical method was used to detect intracellular cholesterol ester, screening appropriate ox-LDL, and FIS concentration. Oil red O staining displayed accumulation of lipids changed by FIS in the foam cells. Then established proteomic maps of foam cells before and after treatment with FIS by bi-directional electrophoresis, mass spectrometry was adopted to identify differences in the expression of proteins. The expression of Cyt b5 was verified by Western blotting. Results: In our study, 20 μg/mL ox-LDL can successfully induce foam cells, as well as intervention of 100 μg/mL FIS would significantly decrease cholesterol ester and lipid accumulation within the foam cells. Proteomic experiment showed that foam cells treated by FIS had a lower expression of nuclear receptor, calreticulin and transcription elongation factor B, higher levels of glutathione S-transferase, cytochrome b5, Prelamin A/C, NADH dehydrogenase (ubiquinone) 2 flavin protein, lecithin-cholesterol acyltransferase, 78 kDa glucose regulation protein, supervillin, and heat shock protein 60. FIS can significantly improve the expression of Cyt b5 by WB. Conclusion: These data suggest that FIS can significantly inhibit foam cells formation by enhancing the cellular antioxidant and anti-inflammatory capabilities, reducing cellular stress response, as well as decreasing accumulation of intracellular cholesterol, regulation of apoptosis and enhanced immunity to prevent atherosclerosis.

El ácido nicotínico aumenta el transporte celular de colesterol de las lipoproteínas de alta densidad en pacientes con hipoalfalipoproteinemia / Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia

Background: Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. Aim: To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. Material and Methods: In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Results: Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Conclusions: Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

Update on the Pharmacologic Agents for Dyslipidemia / 임상당뇨병

Although statins have demonstrated consistent and strong effects on cardiovascular prevention, non-statin drugs have failed to show additional clinical benefit. Consequently, statins are currently recommended as first-line therapy in dyslipidemia. On the contrary, non-statin drugs are indicated in limited cases in which statins are not sufficiently effective or intolerable. A recent trial on ezetimibe provides evidence supporting further prescription of this agent. Proprotein convertase subtilisin-kexin type 9 inhibitors have strong low-density lipoprotein-cholesterol-lowering effects and were just approved in Western countries. However, results of clinical outcomes are not yet available. Other non-statin lipid-modifying agents have their own roles and limitations. Thus, it is important to have correct knowledge on these agents for optimal treatment of dyslipidemic patients.

Effects of total flavonoids from Dracocephalum moldovica on formation of mouse peritoneal macrophage-derived foam cells and study on their mechanisms / 中草药

Objective: To study the effects of total flavonoids from Dracocephalum moldovica on the formation of mouse peritoneal macrophage-derived foam cells and their possible mechanisms. Methods: The mouse peritoneal macrophages were induced with oxidized low density lipoprotein (Ox-LDL) to establish foam cell model, and were intervened with different concentration of total flavonoids from D. moldovica. The foam cells were observed by oil red O staining and the contents of cholesterol ester in cells were detected by fluorescence spectrophotometric method. The expression levels of acyl-coenzyme A, cholesterol acyltransferase-1 (ACAT-1) mRNA in cells and scavenger receptor A (SR-A) on cells were determined using real-time quantitative PCR (RT-qPCR) and flow cytometry, respectively. Results: The Ox-LDL-induced formation of foam cells, accumulation of cholesterol ester in cells, and the expression levels of ACAT-1 mRNA in cells and SR-A on cells were significantly inhibited by total flavonoids from D. moldovica, which showed a tendency toward a dose-dependent manner. Conclusion: These data suggest that total flavonoids from D. moldovica could inhibit the formation of macrophage-derived foam cells, which is probably one of the underlying mechanisms of the total flavonoids for clinical treatment of atherosclerosis.

Cholesterol ester transfer protein regulates the hepatic SR-B1 mRNA expression in mice / 中华内分泌代谢杂志

The effect of cholesterol ester transfer protein(CETP) on SR-B1 mRNA expression in mouse liver was investigated.The results demonstrated that CETP transgenic mice showed lower serum total cholesterol and high density lipoprotein-cholesterol levels but higher total cholesterol and cholesterol ester content in liver when compared with wild type mice(P＜0.05).The expression of SR-B1 mRNA in liver of CETP transgenic mice was significantly lower as compared with the control group(P＜0.05).

Inhibición de la proteína de transferencia de ésteres de colesterol para el manejo de la enfermedad cardiovascular ateroesclerótica: el segundo acto "Una esperanza que renace" / Cholesteryl ester transfer protein inhibition in the management of atherosclerotic cardiovascular disease: second act "A rebirth of hope"

Despite the clinical use of statins to reduce serum levels of LDL cholesterol and treat atherosclerotic cardiovascular disease, a high proportion of patients remain at significant residual cardiovascular risk. In this context, low HDL cholesterol levels are an additional risk factor and intervention studies suggest that a fraction of the cardiovascular protection achieved with pharmacotherapy is explained specifically by the increase in serum levels of HDL cholesterol. Pharmacological inhibitors of the cholesteryl ester transfer protein (CETP) can induce a significant elevation in HDL cholesterol and, potentially, lead to better control of residual cardiovascular risk beyond the benefit demonstrated by statins. While the use of torcetrapib had unexpected side effects, dalcetrapib and anacetrapib are new CETP inhibitors with a better safety profile and are currently under study to evaluate their effects on vascular lesions and clinical events in patients at high cardiovascular risk. If these studies show positive findings, we will witness a new biomedical advance as significant as was the clinical.

Association between cholesteryl ester transfer protein-TaqIB polymorphism and coronary heart disease / 中国医师进修杂志

Objective To determine the frequency of the cholesteryl ester transfer protein (CETP)-TaqIB polymorphism and investigate its relationship with plasma lipid levels and coronary hert disease(CHD). Methods Two hundred and thirty-eight patients with CHD (CHD group) and 203 age-matched controls( control group) were selected, the CETp-TaqIB mutation was detected by restriction fragment length polymorphism of the CETP gene. Results In the total subjects, the frequency of B1 and B2 alleles were 59.4%(262/441 ) and 40.6%( 179/441 ) respectively. Compared with that in control group, the frequency of CETP genotype BIBI was higher in CHD group [39.9%(95/238) vs 29.6% ( 60/203 ), P<0.05], and the frequency of B1B2 was lower in CHD group [44.1%(105/238) vs 53.7%(109/203), P< 0.05]. Compared with that in the B2 homozygotes, high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo)A I level were significantly lower in the B1 homozygotes [(1.19±0.36) mmol/L vs (1.38±0.39) retool/L,( 1.17±0.33 ) g/L vs ( 1.30±0.31 ) g/L, P<0.05]. The B 1 homozygotes was associated with higher degree of cononary stenosis than the B2 carriers (P<0.05 ). There was no significant association between CETP-TaqIB genotype and the risk of CHD (P=0.147). Conclusions CETP-TaqIB polymorphism affects the concentrations of lipaproteins. There are significant associations between the B1 homozygotes and lowerHDL-C and apo A I levels. The B1 allele is not an independent risk factor for CHD.

Progress on the drugs for regulating high-density lipoprotein / 中国临床药理学与治疗学

Atherosclerosis (AS) is pathologically important basis of many kinds of coronary atherosclerosis disease (CAD). It can be substantially protected by raising high-density lipoprotein (HDL).In view of mechanism, drugs for raising HDL include: cholesterol ester transfer protein inhibitors, peroxisomal proliferator-activated receptor agonists, liver X-activated receptor agonists, farnesoid X receptor antagonists or agonists, lipoprotein lipase activators, niacin, and phenytoin and lecin : cholesterol acyltransferase activators, etc. This review aimed to the progress of drugs for regulating high-density lipoprotein and their mechanism, in view of clinical and preclinical aspects.