Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

BACKGROUND: Tacrolimus (Tac) can cause impaired insulin release and dyslipidemia, and may affect the development of post-transplant diabetes mellitus. However, these effects on insulin sensitivity and lipid profile have not been compared in renal transplant recipients receiving traditional twice-daily tacrolimus (TacBID) or cyclosporine and those receiving once-daily prolonged release formulation of tacrolimus (TacOD). METHODS: We conducted an observational prospective study of 15 stable non-diabetic renal transplant recipients to observe the changes in insulin sensitivity and lipid profiles for 1 year at a tertiary hospital. We evaluated the levels of hemoglobin A1c, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, apolipoprotein A1, apolipoprotein B, serum creatinine, fasting plasma glucose, fasting insulin, homeostatic model assessment of β-cell (HOMA-β) and HOMA-insulin resistance index at baseline and at 2 and 4 months. To analyze differences in parameters, we conducted a Wilcoxon rank sum test and general linear model (GLM)-repeated measures analysis of variance (ANOVA) in both groups (cyclosporine to TacOD conversion group/TacBID to TacOD conversion group). RESULTS: At baseline, parameters did not differ between groups. GLM-repeated measures ANOVA revealed no change in insulin sensitivity or lipid profile after conversion at baseline or at 2 and 4 months. There were no complications after conversion from standard TacBID or cyclosporine to TacOD. CONCLUSIONS: There was no change in insulin sensitivity or lipid profile in renal transplant recipients. Any conversion from TacBID to TacOD should be performed in a controlled manner under close surveillance.
Apolipoprotein A-I ; Apolipoproteins ; Blood Glucose ; Cholesterol ; Creatinine ; Cyclosporine* ; Diabetes Mellitus ; Dyslipidemias ; Fasting ; Insulin Resistance* ; Insulin* ; Kidney Transplantation ; Linear Models ; Lipoproteins ; Prospective Studies ; Tacrolimus* ; Tertiary Care Centers ; Transplant Recipients* ; Triglycerides

OBJECTIVETo screen and identify serum biomarkers for childhood hepatoblastoma (HB).

METHODSThe serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins.

RESULTSAfter SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group.

CONCLUSIONSApo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

Apolipoprotein A-I ; blood ; genetics ; Biomarkers ; blood ; Child, Preschool ; Early Detection of Cancer ; Female ; Hepatoblastoma ; blood ; diagnosis ; Humans ; Infant ; Liver Neoplasms ; blood ; diagnosis ; Male ; Real-Time Polymerase Chain Reaction ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats.

METHODSA rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups: a model group (MOD); a berberine group [BBR, 156 mg/(kg day)]; Hdber groups, which were treated with different doses of Hdber [78, 39 and 19.5 mg/(kg day)]; and a simvastatin group [SIM, 4 mg/(kg day)]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acid (FFA), apolipoprotein AI(Apo-AI) and apolipoprotein B (Apo-B) were examined. The protein expressions of low-density lipoprotein receptor (LDL-R), sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) in liver tissues were determined by Western blot analysis.

RESULTSCompared with the control group of rats, the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9 protein in their liver tissues (P<0.01). In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdber reversed the blood lipid profile changes (P<0.05 or P<0.01), decreased the expression levels of PCSK-9 proteins (P<0.01), and increased the expression levels of LDL-R proteins in the hyperlipidemic rats (P<0.01). These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.

CONCLUSIONSHdber is effective in the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.

Animals ; Apolipoprotein A-I ; blood ; Apolipoproteins B ; blood ; Berberine ; analogs & derivatives ; pharmacology ; therapeutic use ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Hyperlipidemias ; blood ; drug therapy ; Lipids ; blood ; Liver ; drug effects ; metabolism ; Male ; Proprotein Convertase 9 ; Rats, Wistar ; Receptors, LDL ; metabolism ; Serine Endopeptidases ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism

OBJECTIVETo investigate the possible effects of apolipoprotein A1 gene (APOA1) rs670 and rs5069 polymorphisms on plasma lipid profiles in healthy adolescents with different body mass index (BMI).

METHODSTotally 723 adolescents were divided into four groups according to their BMI: group 1[BMI =(17.80 ± 0.75)kg/m2], group 2[BMI = (19.39 ± 0.32) kg/m²], group 3[BMI = (20.68 ± 0.43) kg/m²], and group 4[BMI=(23.40 ± 2.05) kg/m²]. Height, weight, waist circumference, hip circumference, blood pressure, heart rate, plasma lipids, and blood glucose were determined, BMI and waist to hip ratio (W/H ratio) were calculated,and genome DNA was extracted for analyzing the genotypes of the APOA1 rs670 and rs5069 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism.

RESULTSNo significant differences in height, weight, BMI, waist circumference, hip circumference, W/H ratio, blood pressure, heart rate, plasma lipids, and blood glucose between APOA1 rs670 or rs5069 genotypes were observed among group 1, group 2, and group 3. In group 4, A carriers of the rs670 polymorphism had significantly higher systolic blood pressure (P=0.017) and blood glucose levels (P=0.009) than the adolescents with the GG genotype. T carriers of the rs5069 polymorphism had significantly higher height (P=0.013), weight (P=0.011), and hip circumference (P=0.026) than the adolescents with the CC genotype.

CONCLUSIONSIn healthy adolescents with higher BMI, APOA1 rs670 polymorphism is associated with systolic blood pressure and blood glucose levels. The elevation of systolic blood pressure and blood glucose levels in A carriers of APOA1 rs670 polymorphism may be favorably modulated by weight loss.

Adolescent ; Apolipoprotein A-I ; genetics ; Body Mass Index ; Female ; Humans ; Lipids ; blood ; Male ; Polymorphism, Genetic

This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100), ApoAI, high density lipoprotein (HDL) and its subclasses could be improved by controlling the blood glucose. Fifty-three patients with newly diagnosed type 2 diabetic were divided into four groups, diet and exercise group (n = 13), continuous subcutaneous insulin infusion (CSII) group (n = 14), multiple daily insulin injection group (MDI, n = 13), and oral hypoglycaemic agents group (n = 13). Fasting blood glucose (FPG), glycated hemoglobin A1c (HbA1c), lipid profiles, ApoB100, ApoAI and HDL subclasses were measured at beginning and a month later. Forty-three patients finished the testing. The levels of FPG, HbA1c, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and ApoB100 were decreased significantly (P < 0.05) in all groups, and ApoAI/ApoB100 increased obviously (P < 0.05). Comparatively matured HDL subclasses such as HDL2b were increased (P < 0.05), and comparatively infantile HDL subclasses such as HDL3b were decreased (P < 0.05). Therapy with hyperglycemic agents improved TG, TC, LDL-C, ApoB100, ApoAI/ApoB100, and HDL2b significantly (P < 0.05), but intervention with the diet and exercise group alone did not improve lipid profiles, apolipoproteins, and HDL subclasses (P > 0.05). Meanwhile, therapy with insulin intensive therapy (MDI, CSII) group had the most powerful effect on decreasing ApoB100 concentration (P < 0.05). The results suggested that lipid profiles, apolipoproteins, and quantity and quality of HDL subclasses might be improved by blood glucose controlling.
Adult ; Aged ; Apolipoprotein A-I ; blood ; Apolipoprotein B-100 ; blood ; Blood Glucose ; metabolism ; Cholesterol, HDL ; blood ; classification ; Diabetes Mellitus, Type 2 ; blood ; Female ; Humans ; Lipids ; blood ; Male ; Middle Aged

BACKGROUNDAlteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.

METHODSOverall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis.

RESULTSCompared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21 ± 8.44) µg/ml vs. (10.95 ± 5.95) µg/ml, P = 0.003) in HDL and a significant increase in the amount of log SAA (1.21 ± 0.46 vs. 1.51 ± 0.55, P < 0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (β = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.

CONCLUSIONSThis study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

Adult ; Aged ; Apolipoprotein A-I ; analysis ; Coronary Disease ; blood ; etiology ; Female ; Humans ; Lipoproteins, HDL ; analysis ; blood ; Male ; Middle Aged ; Serum Amyloid A Protein ; analysis

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.
Adult ; Aged ; Apolipoprotein A-I/*blood ; Apolipoproteins B/*blood ; Area Under Curve ; Carotid Stenosis/*radiography ; Coronary Stenosis/*radiography ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; ROC Curve ; Tomography, X-Ray Computed

PURPOSE: This study was conducted to determine the association between intake of milk and dairy products as well as calcium and biomarkers related to lipid metabolism in Korean female patients with type 2 diabetes. MATERIALS AND METHODS: A cohort of 509 female subjects (mean age: 59.0 years; range: 35-80 years) was recruited from Huh's Diabetes Clinic in Seoul between 2005 and 2010. Dietary intake was assessed using a validated food-frequency questionnaire. Subjects were divided into three groups on the basis of their daily intake of milk and dairy products [<50 g/day (0<50 g/day), 50-200 g/day, and >200 g/day (>200-1201 g/day)] and then further divided into two groups according to their daily calcium intake: below and above the estimated average requirement (EAR). RESULTS: After adjustment for age, body mass index, energy intake, exercise, use of nutritional supplements and cholesterol medication, the level of serum high-density lipoprotein (HDL)-cholesterol was significantly higher in subjects with milk and dairy products consumption of >200 g/day than in subjects in the other two groups. Those subjects with a milk and dairy products consumption of >200 g/day had significantly higher levels of apolipoprotein A-1 and a significantly lower atherogenic index than the other two groups. Patients with a calcium intake above the EAR exhibited a significantly greater serum HDL-cholesterol level than those with a calcium intake below the EAR. CONCLUSION: Milk and dairy products, good sources of calcium, play a positive role in lipid profiles in female patients with type 2 diabetes.
Adult ; Aged ; Aged, 80 and over ; Animals ; Apolipoprotein A-I/blood ; Biological Markers/metabolism ; *Calcium, Dietary ; Cholesterol, HDL/blood ; Diabetes Mellitus, Type 2/*metabolism ; Diet ; Female ; Humans ; *Lipid Metabolism ; Middle Aged ; *Milk

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.
Acute Disease ; Adult ; Apolipoprotein E2/*genetics ; Apolipoprotein E3/*genetics ; Biological Markers/blood ; Combined Modality Therapy ; Diet, Fat-Restricted ; Fatty Acids, Omega-3/therapeutic use ; Female ; Fluid Therapy ; Genetic Predisposition to Disease ; Humans ; Hyperlipoproteinemia Type I/blood/diagnosis/enzymology/*genetics/therapy ; Lipids/blood ; Lipoprotein Lipase/genetics ; Pancreatitis/diagnosis/*etiology/therapy ; Parenteral Nutrition, Total ; Phenotype ; Pregnancy ; Pregnancy Complications/blood/diagnosis/enzymology/*genetics/therapy ; Recurrence ; Tomography, X-Ray Computed ; Treatment Outcome