Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Correlation between serum cystatin C and lipid level in patients with chronic heart failure / 中南大学学报(医学版)

OBJECTIVES@#Serum cystatin C (Cys C) and blood lipid levels are related to the occurrence and development of chronic heart failure (CHF). However, there are few reports on the correlation between blood lipid level and serum Cys C level in patients with CHF. The aim of this study is to explore the correlation between serum Cys C level and blood lipid level in patients with CHF, and to provide valuable reference for clinical diagnosis and treatment of CHF.@*METHODS@#A total of 336 CHF patients who were hospitalized in the Department of Cardiovascular Medicine of Shaanxi Provincial People's Hospital from October 2017 to July 2018 were included and they were divided into a Cys C normal group (n=180) and a Cys C abnormal group (n=156) according to serum Cys C level of the patients. The general data, laboratory indicators, and cardiac ultrasound results were compared between the 2 groups. Pearson correlation analysis was used to detect the correlation between serum Cys C level and blood lipid level and other factors, and the data related to Cys C were further analyzed by multivariate logistic regression.@*RESULTS@#Compared with the Cys C normal group, patients in the Cys C abnormal group had lower left ventricular ejection fraction (LVEF) (P<0.001), older age (P=0.030), higher incidence rate of diabetes and smoking index (P=0.002 and P=0.003, respectively). The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and total bilirubin (TBIL) were higher (all P<0.001), while the levels of high density lipoprotein (HDL), apolipoprotein (Apo) A, and albumin (ALB) were lower (P<0.001, P=0.001, and P=0.003, respectively) in the Cys C abnormal group. Pearson correlation analysis showed that serum Cys C level was negatively correlated with platelet count, HDL, Apo A, ALB, and LVEF. It was positively correlated with smoking index, mean platelet volume, neutrophil ratio, BUN, and TBIL (all P<0.05). The results of multivariate logistic regression analysis showed that the decreased HDL level was a risk factor for the abnormality of serum Cys C in patients with CHF (OR=0.119, P=0.003), while Apo A was not a risk factor for its abnormality (P=0.337).@*CONCLUSIONS@#HDL might be the only blood lipid index associated with abnormal serum Cys C in patients with CHF.

Clinical characteristics of children with atopic dermatitis and change in serum levels of Apo A1, 25(OH)D and EDN / 中国医师杂志

Objective:To investigate the clinical characteristics of children with atopic dermatitis (AD) and the changes in serum levels of apolipoprotein A1 (Apo A1), 25-hydroxyvitamin D [25(OH)D] and eosinophil derived neurotoxin (EDN).Methods:200 children with AD treated in Zhuzhou Central Hospital from January 2016 to December 2019 were selected retrospectively as AD group and 100 healthy children as control group. The clinical characteristics of children with AD were analyzed, and the differences in serum Apo A1, 25 (OH)D and EDN levels between two groups were compared. The relationships between serum Apo A1, 25(OH)D, EDN levels and severity of AD were explored.Results:The male to female composition ratio of 200 AD patients was 1.41∶1, and the age of onset <3 months was the highest (64.50%). Inhalation allergens were detected in 118 cases (59.00%) and ingestion allergens in 82 cases (41.00%). The levels of Apo A1 and EDN in AD group were significantly higher than those in control group, while the level of 25(OH)D was significantly lower than that in control group ( P<0.05). With the aggravation of the disease, the serum Apo A1 and EDN levels in AD children increased gradually, while the serum 25(OH)D level decreased significantly (all P<0.05). Severity Scoring of Atopic Dermatitis (SCORAD) was positively correlated with Apo A1 and EDN levels ( P<0.05), and was negatively correlated with 25(OH)D level (all P<0.05). Conclusions:Apo A1, 25 (OH)D and EDN are involved in the pathogenesis of AD in children, and their serum levels are closely related to the severity of AD.

Olanzapine causes non-alcoholic fatty liver disease via inhibiting the secretion of apolipoprotein A5 / 中南大学学报(医学版)

OBJECTIVES@#Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD.@*METHODS@#This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively.@*RESULTS@#After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced.@*CONCLUSIONS@#The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.

The value of serum levels of Apo B/A1, MAP1-LC3 and ICAM-1 in early assessment of acute pancreatitis / 中华急诊医学杂志

Objective:To investigate the early evaluation potential of serum levels of apolipoprotein B/apolipoprotein A1 (Apo B/A1), microtubule-associated protein 1-light chain 3 (MAP1-LC3) and intercellular adhesion molecule-1 (ICAM-1) in acute pancreatitis (AP) patients.Methods:A total of 413 AP patients who were treated at the Second Affiliated Hospital of Anhui Medical University between January 2019 and August 2020 were enrolled. Serum samples were collected from AP patients within 24 h of admission. Patients were divided into the non-severe acute pancreatitis (Non-SAP, n=315) and severe acute pancreatitis (SAP, n=98) groups according to the severity of the disease. Sixty healthy controls were recruited. The differences of serum Apo B/A1, MAP1-LC3 and ICAM-1 among the three groups were compared by one-way analysis of variance, and the correlation between Apo B/A1, MAP1-LC3 and ICAM-1 and the severity of AP was analyzed by Pearson correlation analysis. Sensitivity and specificity in assessing AP severity were predicted by receiver operating characteristic curve (ROC). Results:The early levels of Apo B/A1, MAP1-LC3 and ICAM-1 were all significantly higher for AP patients than for healthy controls ( P<0.05), and the levels of Apo B/A1, MAP1-LC3 and ICAM-1 in SAP patients were significantly higher than those in non-SAP patients[Apo B/A1: 2.21±1.40 vs. (0.96±0.34); MAP1-LC3: 0.92±0.29 vs. (0.48±0.24) ng/mL and ICAM-1: (235.57±54.50 ) vs. (120.28±61.69)ng/mL; P<0.05]. Pearson correlation analysis showed that levels of Apo B/A1, MAP1-LC3 and ICAM-1 were positively correlated with the first Ranson score after admission ( P<0.05), and ICAM-1 showed the highest degree of correlation with AP severity ( r=0.519). Areas under the receiver operating characteristic curve (AUROC) were 0.769 for Apo B/A1, 0.811 for MAP1-LC3, 0.828 for ICAM-1, and 0.938 for combined detection. Conclusions:Serum levels of Apo B/A1, MAP1-LC3 and ICAM-1 within 24 h after admission are significantly correlated with the severity of AP, which has clinical significance for early prediction of the severity of AP.

Lipoprotein (A) biomarkers for clinical practice / Монголын Анагаах Ухаан

@#A lot of factors can cause coronary heart disease and ischemic stroke including external risk factors such as tobacco, alcohol consumption, decreased physical activity, obesity while arterial maintenance, high blood sugar, increased LDL are internal risk factors. We can reduce our external risk factors by changing our lifestyle. Recent studies have shown increased blood Lp(a) levels are independent risk factor for cardiovascular disease. After 1987, the number of publications has increased since the cDNA homology sequence of Lp(a) and plasminogen 2 was identified. Lp(a) is protein complex consisting from apolipoprotein, phospholipid, free cholesterol, cholesterol esters and tryglyceride. Apoliprotein is a lipid that binds with lipoprotein. Lipoproteins have water-soluble and fat-soluble parts, and those parts bind to lipids and are transported in the bloodstream.How is elevated Lp(a) a risk factor for cardiovascular disease? How much does lowering Lp(a) reduce CVD risk factors? If high Lp(a) concentrations are present, mitigation measures are outlined below.

Hypertriglyceridemia promotes dysfunctions in high-density lipoprotein increasing the cardiovascular risk

Abstract Hypertriglyceridemia is associated with several metabolic diseases. The triglycerides (TG) disrupt the cholesterol reverse transport and contribute to increased levels of low-density lipoprotein (LDL). High-density lipoprotein (HDL) acts in cholesterol reverse transport as an anti-inflammatory and antioxidant. This study aims to investigate the role of hypertriglyceridemia in the functionality of HDL. Individuals were divided into 4 groups based on high or low HDL-c and triglycerides levels. Biochemical and anthropometric analysis were performed. This study demonstrated that triglycerides promote dysfunctions on HDL, increasing the cardiovascular risk. Blood pressure was higher in subjects with low HDL. Women presented higher levels of HDL-c and low percentage of fat mass. The highest levels of triglycerides were observed in older age. In addition, high levels of triglycerides were associated with higher total cholesterol and LDL-c levels, non-HDL-c, non-esterified fatty acids, and blood glucose, increasing in the ratio of non-HDL-c/HDL-c and ApoB/ApoA-I. The increase of triglycerides levels progressively impairs the antioxidant capacity of HDL, probably due to a higher occurrence of fatty acid peroxidation in individuals with hypertriglyceridemia. Patients with high HDL and low TG levels increased the Lag Time. Furthermore, a positive correlation was found between TG versus HDL particle size, variables that depend on age and anthropometric parameters.

ERα promotes transcription of tumor suppressor gene / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Apolipoprotein A-I (ApoA-I), the main protein component of high-density lipoprotein (HDL), plays a pivotal role in reverse cholesterol transport (RCT). Previous studies indicated a reduction of serum ApoA-I levels in various types of cancer, suggesting ApoA-I as a potential cancer biomarker. Herein, ectopically overexpressed ApoA-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects, inhibiting cell proliferation and migration. Subsequent studies on the mechanism of expression regulation revealed that estradiol (E2)/estrogen receptor α (ERα) signaling activates

Value of neutrophil-lymphocyte ratio combined with apolipoprotein A-I level in predicting the severity of acute pancreatitis in the early stage after admission / 临床肝胆病杂志

ObjectiveTo investigate the value of neutrophil-lymphocyte ratio (NLR) combined with apolipoprotein A-I (ApoA-I) level in predicting the severity of acute pancreatitis (AP). MethodsA retrospective analysis was performed for 460 patients with AP who were admitted to The Affiliated Hospital of Southwest Medical University from January 2015 to December 2019, among whom 250 had mild acute pancreatitis (MAP), 166 had moderate-severe acute pancreatitis, and 44 had severe acute pancreatitis (SAP). Related clinical data were collected, including basic information, laboratory markers (neutrophil count, lymphocyte count, serum triglyceride, serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, ApoA-I, and apolipoprotein B), and scores (Ranson, BISAP, and MCTSI). A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups; a logistic regression analysis was performed for the variables with statistical significance in univariate analysis; a Spearman correlation analysis was performed to investigate the correlation between data. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of indices, and MedCalc software was used to investigate whether there was a significant difference in diagnostic efficiency. ResultsThere were significant differences in NLR and ApoA-I level between the groups with different severities of AP (χ2= 64.124, F=40.277, P＜0.001). On admission, NLR was positively correlated with Atlanta grading, Ranson score, MCTSI score, and BISAP score (r=0.370, 0.129, 0.260, and 0.122, all P＜0.05), and ApoA-I level was negatively correlated with Atlanta grading, Ranson score, MCTSI score, and BISAP score (r=-0.358, -0.220, -0.297, and -0.251, all P＜0.05). NLR was an independent risk factor for non-MAP (odds ratio ［OR］=1.104, 95% confidence interval ［CI］: 1.070-1.140, P＜0.001), while ApoA-I was an independent protective factor against non-MAP (OR=0.138, 95% CI: 0.070-0.264, P＜0.001); NLR was an independent risk factor for SAP (OR=1.163, 95% CI: 1.107-1.222, P＜0.001), while ApoA-I was an independent protective factor against SAP (OR=0013, 95% CI: 0.003-0.056, P＜0.001). NLR had an area under the ROC curve (AUC) of 0.700 (95% CI: 0.656-0.742, P＜0.001) in predicting non-MAP; ApoA-I had an AUC of 0.684 (95% CI: 0.640-0.726, P＜0.001) in predicting non-MAP; NLR combined with ApoA-I had an AUC of 0.748 (95%CI: 0.706-0.787, P＜0.001) in predicting non-MAP. NLR combined with ApoA-I had a better value than NLR or ApoA-I alone in predicting non-MAP (Z=3.439 and 2.462, both P＜0.05). NLR had an AUC of 0.752 (95% CI: 0.710-0.791, P＜0.001) in predicting SAP; ApoA-I had an AUC of 0.797 (95% CI: 0.757-0.833, P＜0.001) in predicting SAP; NLR combined with ApoA-I had an AUC of 0.857 (95% CI: 0.822-0.888, P＜0.001) in predicting SAP. NLR combined with ApoA-I had a better value than NLR or ApoA-I alone in predicting SAP (Z=3.171 and 2.630, both P＜0.05). ConclusionNLR combined with ApoA-I can be used as a good indicator for predicting the severity of AP in the early stage after admission.

Identifying the role of apolipoprotein A-I in prostate cancer / 亚洲男科学杂志(英文版)

Although localized prostate cancer (PCa) can be cured by prostatectomy and radiotherapy, the development of effective therapeutic approaches for advanced prostate cancer, including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), is lagging far behind. Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need. Here, we report that apolipoprotein A-I (ApoA-I), the major component of high-density lipoprotein (HDL), is upregulated in PCa based on both bioinformatics and experimental evidence. The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells. Molecularly, ApoA-I is regulated by MYC, a frequently amplified oncogene in late-stage PCa. Altogether, our findings have revealed a novel indicator to predict prognosis and recurrence, which would benefit patients who are prone to progress to metastasis or even NEPC, which is the lethal subtype of PCa.

Advances in ApoA- I mimic peptides against atherosclerosis / 中国药理学通报

Apolipoprotein A-I (ApoA-I), the main protein component of high density lipoprotein (HDL) , which plays a key role in the process of reverse cholesterol transport (RCT) , is considered as an important anti-atherosclerosis (As) drug target. ApoA- I mimic peptides developed based on its a-helix, and HDL mimic peptides that developed by recombinant ApoA- I have entered clinical trials, exhibiting favorable RCT promotion and anli-As activity. The paper reviewed the advances in the structure and function of ApoA- I , the molecular interaction mechanism between ApoA-1 and ABCA1 ( ATP-binding cassette transporter Al) , LCAT (lecithin cholesterol acyl transferase) and SR-B1 (scavenger receptor class B type 1) , and anti- As activity of ApoA- I mimic peptides, which would provide references for anli-As new drug development based on ApoA- I mimic peptides.

Study of maternal serum lipid profile and apolipoprotein a levels and its correlation with fetal growth restriction

Background: This study was aimed to estimate maternal serum lipid profile and apolipoprotein A levels in pregnancies complicated with FGR and to compare the levels with the levels in normal pregnancies.Methods: A prospective observational study was conducted in Lady Hardinge Medical College, New Delhi, in a study group consisting of 30 pregnant women at gestation 32-34 weeks with ultrasound diagnosed FGR and control group consisting of 30 age and gestation matched uncomplicated pregnant women. Maternal serum lipid profile and apolipoprotein A levels were measured and compared between the two groups.Results: Total serum cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol and Apolipoprotein A were significantly lower in FGR group compared to normal controls. Mean±SD of total cholesterol was found to be 199.17±49.06 mg/dl in cases and 244.10±53.17 mg/dl in controls. Mean±SD of triglyceride was 200.53±60.25 mg/dl in cases compared to 304.13±69.12 mg/dl in controls. Mean±SD of LDL-Cholesterol was 98.19±37.91 mg/dl in cases and 127.07±47.84 mg/dl in controls. Mean±SD of VLDL-cholesterol was 40.11±12.05 mg/dl in cases and 60.83±13.82 mg/dl in controls. Mean±SD of Apolipoprotein A was 147.71±16.40 mg/dl in cases compared to 163.30±16.07 mg/dl in controls. HDL-cholesterol did not change significantly as its mean±SD was 60.87±15.18 mg/dl in FGR group and 56.20±16.07 mg/dl in control group.Conclusions: The decreased levels of total cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol and apolipoprotein A levels may be used as biochemical marker for detection of FGR.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Correlation between Pretreatment Serum Apolipoprotein Level and Prognosis of Small Cell Lung Cancer Patients / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death, and small cell lung cancer (SCLC) has a poor prognosis in all types of lung cancer. This study evaluated the relationship between pretreatment serum apolipoprotein levels and prognosis in patients with SCLC, seeks a new index can guide diagnosis and treatment of SCLC.@*METHODS@#This study retrospectively analyzed the clinical data of 122 patients with SCLC. The clinical results of patients with serum apolipoprotein levels within 2 weeks before treatment were collected, including apolipoprotein AI (ApoA-I), apolipoprotein B (ApoB), and the ratio of apolipoprotein B to apolipoprotein AI (ApoB/ApoA-I). Patients' progression-free survival (PFS) and overall survival (OS) are the main outcome indicators. The best critical to determine the index's value by X-tile tool. For survival analysis, Kaplan-Meier method was used for analysis, and Cox regression analysis method was used for single factor analysis and multifactor analysis.@*RESULTS@#Compared with patients with low ApoA-I levels, patients with high ApoA-I levels (ApoA-I>1.12 g/L) had better OS (21.5 mon vs 12.3 mon, P=0.007) and PFS (7.3 mon vs 5.5 mon, P=0.017). In contrast, patients with higher ApoB/ApoA-I levels had worse median OS than patients with lower ApoB/ApoA-I levels (13.4 mon vs 20.7 mon, P=0.012). Multivariate Cox regression analysis showed that ApoA-I was an independent prognostic factor affecting PFS in SCLC patients (HR=0.67, 95%CI: 0.45-0.99, P=0.043). ApoB/ApoA-I is an independent risk factor for OS in patients with SCLC (HR=1.98, 95%CI: 1.21-3.23, P=0.007).@*CONCLUSIONS@#Serum ApoA-I level and ApoB/ApoA-I level before treatment can be important prognostic factors for SCLC, which is helpful to judge the prognosis of patients.

Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.

Downregulation of apolipoprotein A-IV in plasma & impaired reverse cholesterol transport in individuals with recent acts of deliberate self-harm

Background & objectives: The major limiting factor in the prevention of suicide is the limited knowledge on molecular insights in individuals at risk. Identification of peripheral protein markers which can classify individuals at high-risk of suicide might aid in early diagnosis and effective medical intervention. The aim of the present study was, therefore, to analyze the differential regulation of plasma proteins in individuals with deliberate self-harm compared to controls. Methods: Using two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption-ionization mass spectrometry, differentially expressed plasma proteins were identified in study participants with deliberate self-harm compared to age- and gender-matched controls. The finding was validated using mass spectrometry-based isotope-labelled relative quantification and Western blot analysis in a new set of individuals with deliberate self-harm and controls. Results: The plasma proteomic analysis showed that apolipoprotein A-IV (Apo A-IV ) was downregulated by 2.63-fold (confidence interval: 1.52-4.54) in individuals with deliberate self-harm (n=10) compared to matched controls, which was consistent in mass spectrometry-based relative quantification and Western blot analysis performed in an independent set of individuals with deliberate self-harm (n=18). In addition, plasma levels of total cholesterol, esterified cholesterol and high-density lipoprotein (HDL) were observed to be significantly lower individuals with deliberate self-harm compared to controls. Interpretation & conclusions: Apo A-IV, which plays a crucial role in the esterification of free cholesterol, was found to be downregulated with concomitantly decreased levels of HDL, esterified cholesterol and total cholesterol in individuals with deliberate self-harm compared to matched controls. The present findings might provide a link between the differential regulation of plasma proteins and the previously reported results on altered cholesterol levels in individuals with deliberate self-harm.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Relationship between Serum Lipid Levels and Parkinson's Disease / 中国康复理论与实践

Objective:To investigate the relationship between serum lipids and Parkinson's disease, and its predictive value for Parkinson's disease. Methods:From January, 2016 to November, 2018, 145 patients with Parkinson's disease and other 122 healthy subjects were selected. They were measured the various lipid indexes. Results:Total cholesterol, low density lipoprotein cholesterol, Apolipoprotein A1 (ApoA1) and Apolipoprotein B (ApoB) were less in the patients than in the controls (t > 2.089, P < 0.05). ApoA1 was an independent protective factor from Logistic regression (OR = 0.081, P < 0.01). The most optimal cut-off threshold of ApoA1 was 1.38 mmol/L, with the sensitivity of 0.72 and the specificity of 0.68. Conclusion:The lipid decreased in patients with Parkinson's disease. Low ApoA1 may be a potential independent risk factor for Parkinson's disease, which may be a predictor for it.

Effects of atorvastatin on expression of lipid metabolism- related genes in HepG2 cells / 吉林大学学报(医学版)

Objective: To explore the effects of atorvastatin on the natural antisense transcription of apolipoprotein A1 (apoAl-NAT) in the HepG cells and its influence in the expressions of lipid metabolism related genes. Methods: The HepG cells were intervened with different concentrations (0, 1, 10 and 100 nmol • L-1 ) of atorvastatin, and the 0 nmol • L-1 atorvastatin group was used as control group. The total RNA of HepG cells in various groups were extracted at different time points (6, 12, 24, and 48 h). The mRNA expression levels of lipid metabolism-related genes and apoAl-NAT expression levels were detected by Real-Time PCR method. Results: The morphology of HepG cells in 1 and 10 nmol • L-1 atorvastain groups was normal. Compared with 6 h, the expression levels of apoAl-NAT in the HepG cells in 10 nmol • L atorvastatin group at 12, 24 and 48 h were significantly decreased (P

Correlation between ratio of Apo A1／Apo B and heart failure／ / 心血管康复医学杂志

To analyze the correlation between ratio of apolipoprotein A 1 (ApoA1 )／apolipoprotein B (ApoB) and heart failure (HF).Methods : A total of 150 HF patients treated in our department were divided into NYHA class II group (n＝54) ,class III group (n＝48) and class IV group (n＝48).Their LVEF ,stroke volume (SV) ,cardiac output (CO) ,cardiac index (CI) ,levels of BNP ,serum Apo A1 and Apo B were measured ,and Apo A1／Apo B was calculated ,then correlation analysis was performed .Results : Compared with class II group ,there were significant reductions in LVEF [ (37. 29 ± 6. 25)% vs.(34. 66 ± 5.90)% vs.(32.55 ± 5. 23)%] ,SV [ (36. 40 ± 4.18) ml vs .(34.05 ± 3. 49) ml vs.(31.72 ± 5.44) ml] ,CO [ (3.71 ± 0.59) L／min vs .(3.39 ± 0. 43) L／min vs.(3. 17 ± 0.44) L／min] ,CI [ (2. 16 ± 0.50 ) L· min－1 · m－2 vs.(1. 76 ± 0.37 ) L· min－1 · m－2 vs.(1. 44 ± 0.43) L·min－1 ·m－2 ] ,and ApoA1／ApoB [ (1.17 ± 0.44) vs.(0. 98 ± 0.28) vs.(0. 65 ± 0.24)] in class III group and class IV group ,and those of class IV group were significantly lower than those of class III group ;significant rise in levels of plasma BNP [ (469.23 ± 63. 12) pg／ml vs.(612. 52 ± 80.34) pg／ml vs.(822.96 ± 97.22) pg／ml] in class III group and class IV group ,and those of class IV group were significantly higher than those of class III group ,P＜0.05 or ＜0.01. Pearson correlation analysis indicated that serum Apo A 1／Apo B was significant positively correla‐ted with LVEF ,SV ,CO and CI ( r＝0. 422～0. 603 , P＜0.05 or ＜0.01) ,and significant inversely correlated with plasma BNP level ( r＝ －0. 625 , P＝0.002).Conclusion :The worse the cardiac function is ,the lower serum Apo A1／Apo B is in HF patients .There is positive correlation between them .21－3