Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b

BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer

BACKGROUND: Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. METHODS: We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. RESULTS: In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. CONCLUSIONS: Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.

APO A2 -265T/C Polymorphism Is Associated with Increased Inflammatory Responses in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Apolipoprotein A2 (APO A2) is the second most abundant structural apolipoprotein in high density lipoprotein. Several studies have examined the possible effect of APO A2 on atherosclerosis incidence. Due to the role of inflammation in atherosclerosis, we aimed to determine the relationship between APO A2 -265T/C polymorphism and inflammation as a risk factor in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 180 T2DM patients, with known APO A2 -265T/C polymorphism, were recruited for this comparative study and were grouped equally based on their genotypes. Dietary intakes, anthropometric parameters, lipid profile, and inflammatory markers (i.e., pentraxin 3 [PTX3], high-sensitivity C-reactive protein [hs-CRP], and interleukin 18) were measured. The data were analyzed using an independent t-test, a chi-square test, and the analysis of covariance. RESULTS: After adjusting for confounding factors, in the entire study population and in the patients with or without obesity, the patients with the CC genotype showed higher hs-CRP (P=0.001, P=0.008, and P=0.01, respectively) and lower PTX3 (P=0.01, P=0.03, and P=0.04, respectively) in comparison with the T allele carriers. In the patients with the CC genotype, no significant differences were observed in the inflammatory markers between the obese or non-obese patients. However, regarding the T allele carriers, the plasma hs-CRP level was significantly higher in the obese patients compared to the non-obese patients (P=0.01). CONCLUSION: In the T2DM patients, the CC genotype could be considered as a risk factor and the T allele as a protective agent against inflammation, which the latter effect might be impaired by obesity. Our results confirmed the anti-atherogenic effect of APO A2, though more studies are required to establish this effect.

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

Discovery and identification of serum biomarkers of Wilms' tumor in mice using proteomics technology / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Wilms' tumor (nephroblastoma) is a cancer of the kidneys that occurs typically in children and rarely in adults. Early diagnosis is very important for the treatment and prognosis of the disease. The aim of our study was to discover and identify potential non-invasive and convenient biomarkers for the diagnosis of Wilms' tumor.</p><p><b>METHODS</b>Nude mice were used to construct a Wilms' tumor model by injecting nephroblastoma cells into their bilateral abdomen. We collected 94 serum samples from mice consisting of 45 samples with Wilms' tumor and 49 controls. The serum proteomic profiles of the samples were analyzed via surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The candidate biomarkers were purified by high-performance liquid chromatography, identified by liquid chromatography-mass spectrometry, and validated using ProteinChip immunoassays.</p><p><b>RESULTS</b>We finally retrieved two differential proteins (m/z 4509.2; 6207.9), which were identified as apolipoprotein A-II and polyubiquitin, respectively. The expression of apolipoprotein A-II was higher in the Wilms' tumor group than in the control group (P < 0.01). By contrast, the expression of polyubiquitin was lower in the Wilms' tumor group than in the control group.</p><p><b>CONCLUSION</b>Apolipoprotein A-II and polyubiquitin may be used as potential biomarkers for nephroblastoma in children, and the analysis of apolipoprotein A-II may help diagnose and treat Wilms' tumor.</p>

The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B

BACKGROUND: Apolipoprotein A-II (apoA-II) is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) in Korean adults. METHODS: We analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations. RESULTS: The mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5+/-4.6 mg/dL vs. 31.2+/-4.6 mg/dL, P=0.261). ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956). CONCLUSION: Compared with apoA-I (negative association with MetS) and apoB (positive association with MetS) levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties.

The screening and identification of Apolipoprotein A-II from serum differential proteins in hepatocellular carcinoma patients / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To screen differential proteins in serum from hepatocellular carcinoma (HCC) patients by Proteomic Technology and to purify and identify them.</p><p><b>METHODS</b>Surface enhanced laser desorption Ionization time of flight-mass spectrum (SELDI-TOF-MS) was employed to screen differential proteins in serum from 33 HCC patients and 33 control cases, and then to purify and identify them using isoelectric precipitation, Tricine sodium dodecyl sulphate polyacrylamide gel electrophoresis (Tricine-SDS-PAGE) and high performance liquid chromatography tandem Mass Spectrum (HPLC-MS).</p><p><b>RESULTS</b>65 protein peaks in the range of relative molecular weight from 2,000 to 10,000 were found significant difference (P less than 0.05) between the patient group and control group. Based on these differential protein peaks, diagnostic model for HCC detection was established and its sensitivity and specificity were 100% and 96.97% respectively. Proteins with 8,706.5 and 8,579.2 relative molecular weights (the t value was 2.562 and 2.783 respectively, and P value was 0.013 and 0.015 respectively) out of the 65 differential proteins were purified and identified, and then recognized as Apolipoprotein AII (Apo AII).</p><p><b>CONCLUSION</b>Apo AII is probably a differential protein of HCC and maybe related to the pathogenesis of HCC.</p>

Gel electrophoresis analysis on plasma differential protein in patients with unstable angina of blood-stasis pattern / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To seek the plasma differential proteins in patients with unstable angina of blood-stasis pattern (UA-BSS) for exploring the proteomic specialty in them by way of two-dimensional difference gel electrophoresis (DIGE) detection on plasma of patients and healthy persons.</p><p><b>METHODS</b>Using DIGE and tandem mass spectrometry, comparative proteomic study was conducted on the plasma of 12 UA patients of qi-deficiency and blood-stasis pattern (UA-QBS), 12 UA patients of phlegm-stasis cross-blocking pattern (UA-PSS) and 12 healthy volunteers.</p><p><b>RESULTS</b>Preliminary results showed that Haptoglobin beta chain, DBP, HBB, HBA, Transthyretin, ApoA- I, ApoA-IV were significantly differentially expressed in both patterns, while Haptoglobin alpha1 chain, alpha-1-acid glycoprotein, ApoC-III, ApoA-II, ApoC-II, ApoJ, and Haptoglobin alpha 2 chain were only seen differentially expressed in the UA-PSS patients, alpha1-antitrypsin, Fibrinogen gamma chain, and Fibrin beta were only seen differentially expressed in UA-QBS patients.</p><p><b>CONCLUSION</b>The common proteomics characteristics of patients of QBS and PSS patterns may be correlated with inflammatory reaction and metabolic disturbance (including blood lipid and blood oxygen).</p>

Lipid profiles in patients with systemic lupus erythematosus / 대한내과학회지

BACKGROUND: The aims of this study were the identification of the abnormalities in lipid profiles and the correlations between serum lipid profiles and inflammatory parameters in patients with systemic lupus erythematosus. METHODS: The subjects were 50 patients with systemic lupus erythematosus who have been treated in rheumatology clinic, Yeungnam University Hospital. Serum lipids and apolipoproteins were measured and compared with those of age- and sex-matched controls. In systemic lupus erythematosus group, disease activities were assessed by systemic lupus erythematosus disease activity index and erythrocyte sedimentation rate. RESULTS: All lipid profiles were within normal range but most of lipoprotein levels were higher in patients with systemic lupus erythematosus than controls. Triglyceride, low-density lipoprotein and very-low-density lipoprotein were statistically significant (p=0.001, p=0.023, and p=0.001 respectively). Total cholesterol and low-density lipoprotein were significantly increased in systemic lupus erythematosus patients with proteinuria (>or=100 mg/dL/24hr) than in patients without proteinuria. Total cholesterol and low-density lipoprotein had positive correlations and apolipoprotein A-II had negative correlation with systemic lupus erythematosus disease activity index. Low-density lipoprotein and apolipoprotein B had positive correlations, high-density lipoprotein and apolipoprotein A-II had negative correlations with erythrocyte sedimentation rate. But differences of lipid profiles according to the duration of disease and total doses of steroid were not significant. CONCLUSION: This study showed that triglyceride, low-density lipoprotein, and very-low-density lipoprotein in patients with systemic lupus erythematosus were higher than controls. Total cholesterol and LDL in patients with SLE had positive correlations with disease activities.

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL