Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma

ObjectivesInter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC).Design and methodsThe study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU).ResultsITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P < 0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (≥ 5 cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373–25.300, P = 0.017). A Kaplan–Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (< 80 DU) and a large tumor size compared to that among other HCC patients (P < 0.001), and among patients with high AFP (> 200 ng/mL) and low ITIH4 compared to that among other HCC patients (P = 0.041).ConclusionsSerum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.     

Expression of STK15 mRNA in hepatocellular carcinoma and its prognostic significance

ObjectivesTo investigate whether the STK15 mRNA expression correlates with clinicopathologic features and the prognosis of HCC patients.Design and methodsThree hepatoma cell lines, two normal liver epithelial cell lines, hepatoma tissues, adjacent tumor tissues and normal liver tissues were obtained from 46 HCC patients. Semi-quantitative RT-PCR assays were performed to detect the expression of STK15 mRNA in above cell lines and tissues. Moreover, the expression of STK15 protein in hepatoma tissues, adjacent tumor tissues and normal liver tissues was also examined by immunohistochemical staining. Finally, correlations between STK15 mRNA expression and the clinicopathological features and prognosis of HCC patients were evaluated.ResultsSTK15 mRNA showed higher levels in hepatoma cell lines than in normal liver epithelial cell lines. Moreover, the mean levels of STK15 mRNA and protein expression showed statistical difference between tumor tissues, tumor adjacent tissues and normal liver tissues (P < 0.01). By immunohistochemical analysis, we found that paraffin-embedded archival HCC tissues showed higher expression of STK15 than adjacent tumors and normal liver tissues. Furthermore, HCC patients with higher STK15 mRNA expression showed poorer prognosis than those with lower STK15 mRNA expression. The high level of STK15 mRNA expression was significantly correlated with tumor stage (P = 0.0081), more frequent lymph node (P = 0.0380) or hematogenous metastasis (P = 0.0066), and a higher incidence of cancer-related death (P = 0.0083). Furthermore, the disease-free survival (DFS) and overall survival (OS) rates of HCC patients with higher STK15 mRNA expression group (47.6% and 52.7%) were significantly lower than those of patients with low STK15 mRNA expression group (56.9% and 68.8%, P = 0.0018 and 0.0047).ConclusionsSTK15 mRNA might be a good marker for predicting the prognosis of HCC patients.     

Rapid and quantitative detection of CpG-methylation status using TaqMan PCR combined with methyl-binding-domain polypeptide

ObjectivesTo assess the medical applicability of CpG methylation as molecular markers for cancer diagnosis, we established a new system to determine DNA methylation based on TaqMan PCR combined with a methyl-binding-domain polypeptide 2.Design and methodsWe evaluated the diagnostic applicability of this approach by examining the methylation status of two tumor suppressor genes, RASSF1A and APC, in 10 paired hepatocellular carcinoma (HCC) and the corresponding non-tumor liver tissues.ResultsMethylation levels of total 20 clinical samples measured by the TaqMan PCR assay showed a significantly positive correlation (R = 0.814, P < 0.0005 for RASSF1A, R = 0.736, P < 0.00001 for APC) with those calculated by bisulfite sequencing. The methylated DNA amount measured by our TaqMan PCR system precisely replicated the methylation status estimated by direct sequencing.ConclusionsThis suggests our method may serve as a reliable and easy-to-use tool for cancer diagnosis using methylated genes as biomarkers.     

BCL2L12: A promising molecular prognostic biomarker in breast cancer

ObjectivesBCL2-like 12 (BCL2L12) is a new member of the BCL2 gene family that was discovered and cloned by members of our group and found to be expressed in the mammary gland. Many genes of the BCL2 family were found to be implicated in breast carcinogenesis and to serve as possible prognostic markers. The aim of the present study was the quantification of BCL2L12 mRNA expression in order to assess its value as a prognostic tissue biomarker in breast cancer (BC).Design and methodsBCL2L12 mRNA levels were determined in a statistically significant sample size of cancerous (N = 108) and adjacent non-cancerous (N = 71) breast tissues using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Relative quantification analysis was conducted using the comparative C_T (2^− ΔΔC_T) method, whereas the association between BCL2L12 expression and clinopathological data, disease-free survival (DFS) and overall survival (OS) were estimated by statistical analysis.ResultsBCL2L12 mRNA expression was decreased in malignant samples compared to the histologically normal counterparts (p = 0.012). Significant relationships between BCL2L12 expression and TNM stages (p = 0.009), metastatic potential (p = 0.012), tumor size (p = 0.04) and age (p = 0.024) were observed. Moreover, Kaplan–Meier and Cox univariate analyses indicated that BCL2L12 expression is associated with longer DFS, whereas multivariate analysis pointed out the independent favorable prognostic value of BCL2L12.ConclusionsAccording to our results, BCL2L12 mRNA expression is a favorable prognostic marker of DFS for BC patients, suggesting its possible application as a novel prognostic indicator of this malignancy.     

FOXP1 and SPINK1 reflect the risk of cirrhosis progression to HCC with HBV infection

BackgroundHepatocellular carcinoma (HCC) deriving from cirrhosis with HBV infection harbors higher morbidity and poor prognosis. The diagnosis of HCC at its early stage is essential for improving the effect of treatment and survival rate of patients.MethodAffymetrix GeneChip was practiced to establish gene expression profile and significance analysis of microarray (SAM) as well as prediction analysis of microarray (PAM) was utilized to screen candidate marker genes in tissue of carcinoma and para-cancerous with cirrhosis from 15 hepatitis B virus (HBV) related HCC patients.ResultTotal 497 differential genes were selected by microarray (fold change >2; P value < 0.01). Then 162 significant genes were determined by SAM (fold change −1.46 to 1.28). A number of 8-genes showing “poor risk signature” was validated with threshold of 6.2, which was associated with cirrhosis progressing to HCC. Only 3 down-regulated and 2 up-regulated predictor genes had statistical difference in HCC and cirrhosis groups by RT-PCR (P value < 0.01). Forkhead box protein 1 (FOXP1) and serine protease inhibitor Kazal-type 1 (SPINK1) proteins were found significantly increased in carcinoma tissues than para-cancerous cirrhotic tissues by IH and WB.ConclusionOver-expression of FOXP1 and SPINK1 may participate in the carcinogenesis of HBV related cirrhosis. They could use as potential biomarkers for diagnosing early HCC.     

Receptor for advanced glycation end products (RAGE) and glyoxalase I gene polymorphisms in pathological pregnancy

ObjectivesThe aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy.Design and methodsPolymorphisms of RAGE gene (? 429 T/C, ? 374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy.ResultsNo differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p = 0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r = ? 0.536, p = 0.05).ConclusionsWe did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.     

Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers

BackgroundThere are few blood tests for an efficient detection of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection.MethodsThe abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, α-fetoprotein (AFP) and prothrombin-induced vitamin K absence II (PIVKA-II), and various combinations to detect HCC were evaluated in a training cohort of 164 HCV-infected patients (108 HCCs; 56 non-HCCs). An optimal hybrid detector, built using data for 2 methylated genes (SPINT2 and SRD5A2), AFP, and PIVKA-II, achieved the most satisfactory ability to detect HCC in the training cohort. We evaluated the ability of the optimal hybrid detector to detect HCC in an independent validation cohort of 258 consecutive HCV-infected patients (112 HCCs; 146 non-HCCs) who were newly enrolled in 4 distinct institutes.ResultsIn the validation cohort of 258 patients, accuracy, sensitivity, and specificity of the hybrid detector for detection of HCC were 81.4%, 73.2%, and 87.7%, respectively. Notably, even when detecting HCC ≤ 2 cm in diameter, the hybrid detector maintained markedly high abilities (84.6% accuracy, 72.2% sensitivity, 87.7% specificity). Youden's index (sensitivity + specificity ? 1) for HCC ≤ 2 cm was 0.60, vastly much superior to the 0.39 for AFP at a cut-off value of 20 ng/ml and the 0.28 for PIVKA-II at a cut-off value of 40 mAU/ml.ConclusionsThese results show that the optimal hybrid blood detector can detect HCV-related HCC more accurately.     

Diagnostic value of alpha-1-fetoprotein (AFP) as a biomarker for hepatocellular carcinoma recurrence after liver transplantation

BackgroundAlpha-1-fetoprotein (AFP) is used to monitor progression, evaluate response to therapy and predict recurrence of hepatocellular carcinoma (HCC) in liver transplantation (LTx) patients. To date, the diagnostic value of serum AFP determinations for detecting tumor recurrence in HCC patients after LTx is unclear.ObjectiveA retrospective, single-center, cross-sectional, non-interventional study was performed with the objective of determining post-transplant cut-off AFP values for detecting HCC recurrence post LTx.MethodsUsing receiver operating characteristic (ROC) analyses, post-transplant serum AFP values were evaluated against HCC recurrences in 63 HCC patients who had LTx between November 1995 and December 2011 at the University Medical Center Göttingen (UMG). Optimal and application-independent cut points for predicting tumor recurrence at 1, 3, and 5 years after LTx were determined.ResultsPost-LTx serum AFP was found to represent an independent risk factor (predictor) for HCC relapse. Post-operative AFP cut-off values of 7 μg/l, 6 μg/l, and 6 μg/l, respectively, were determined to be optimal at 1, 3, and 5 years after LTx respectively for predicting a HCC relapse. Using these cut-off values, patients were correctly classified as relapse-positive with a diagnostic sensitivity of 79%, 81%, and 77%, and as relapse-free with a specificity of 82%, 79%, and 69%. The diagnostic accuracy measured by area under the curve (AUC) values ranged from 0.813 to 0.886. However, a limitation is that at a clinically relevant specificity of ≥ 95%, the analyses showed sensitivity values of only 50%, 52%, and 50%, respectively.ConclusionPost-transplant serum AFP may have diagnostic value to detect HCC recurrence after LTx.     

Inverse correlation of ribosomal protein S27A and multifunctional protein YB-1 in hepatocellular carcinoma

ObjectiveThe detection of possible correlation between ribosomal protein RPS27A and multifunctional YB-1 expression in hepatocellular carcinoma (HCC).Design and methodsTissue microarray slides containing totally 80 cores with 19 tissues of HCC, 1 tissue of hepatocholangiocarcinoma, 10 tissues of liver cirrhosis and 10 normal liver tissues in duplicates were analyzed for expression of RPS27A and YB-1 by immunohistochemistry.ResultsAmong each of 10 LC and normal liver tissues all (100%) showed RPS27A positive expression but only 11 out of 19 HCC tissues (57.89%) showed RPS27A positive expression with significant difference compared (P < 0.05) with both LC and normal tissues. We found positive expression of YB-1 in 17 tissues out of 19 HCC tissues (89.47%) but only 4 tissues out of each 10 LC as well as normal liver tissues showed positive expression with significant (P < 0.01) difference compared to HCC tissues. A statistically significant inverse weak correlation (rho = − 0.293) between YB-1 expression and RPS27A expression was found.ConclusionThe present investigation concludes that the ribosomal protein RPS27A was down-regulated in viral induced HCC patients. RPS27A expression was found to have a weak inverse correlation with overexpression of multifunctional protein YB-1 in HCC tissues. This study opens up a new window for YB-1–RPS27A axis in HCC.     

Increased serum brain-derived neurotrophic factor with high-intensity interval training in stroke patients: A randomized controlled trial

BackgroundPhysiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear.ObjectiveThis study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients.MethodsWe included 23 stroke patients with age about 55 years and stroke duration > 24 months; participants completed 36 sessions of exercise training for 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO_2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) VO_2peak. Before and after interventions, we evaluated VO_2peak, peak CO, arteriovenous oxygen difference (AV O_2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O₂Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites).ResultsHIIT induced significant increases in VO_2peak (P = 0.008), CO (P = 0.038), Δ[HHb] (P = 0.046), Δ[THb] (P = 0.046), and serum BDNF level (P = 0.012). The improvement in VO_2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P = 0.031), as was AV O_2diff (P = 0.041), Δ[HHb] (P = 0.027), and serum BDNF level (P < 0.001). HIIT facilitated neuron dendritic protrusions (greater % neurites, P = 0.012) with prominent redistribution of mitochondria.ConclusionAs compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O₂ extraction in stroke patients. Increased cerebral O₂ utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT.ClinicalTrials.gov identifierNCT04135391.     

Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men

BackgroundSingle nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men.MethodSerum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged ≥ 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using T_m-shift allele-specific PCR.ResultsSNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p < 0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p = 0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p = 0.019 and p = 1 × 10^? 5, respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p = 1 × 10^? 5).ConclusionThe genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.     

Predictive value of osteocalcin in bone metastatic differentiated thyroid carcinoma

ObjectivesTo evaluate the diagnostic value of serum osteocalcin in the detection of bone metastases from differentiated thyroid carcinoma (DTC).Design and methodsSerum samples from DTC patients with (DTC BM+, n = 19) or without bone metastases (DTC BM?, n = 19), and matched healthy volunteers (n = 30) were tested for serum osteocalcin with electrochemiluminescent immunoassay.ResultsOsteocalcin was higher in DTC BM+ than in DTC BM? patients (+ 35.8%, p = 0.002), acting as an independent risk factor for bone metastases (R² = 0.142, p = 0.039). The sensitivity was 78.9% and the specificity was 63.2% at a cut-off value of 11.2 μg/L.ConclusionsSerial measurements of osteocalcin could be useful in the detection of bone metastases from DTC.     

Association Between Cardiovascular Autonomic Functions and Time to Death in Patients With Terminal Hepatocellular Carcinoma

ContextA better time-to-death (TTD) prediction can facilitate decision-making processes related to plans for providing effective end-of-life care for patients in hospice wards.ObjectiveTo explore the association of cardiovascular autonomic functions with TTD in patients with terminal hepatocellular carcinoma.MethodsA prospective study was conducted with 33 patients with hepatocellular carcinoma recruited from the hospice ward of a regional hospital in Chiayi county, Taiwan. Serum creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, blood urea nitrogen (BUN), and serum albumin were measured on the admission day. Cardiovascular autonomic functions were evaluated by frequency-domain measures of heart rate variability (HRV) on admission.ResultsTTD was significantly associated with total spectrum power (TP) (r = 0.55, P = 0.001) and high frequency (HF power) (r = 0.44, P = 0.010) of HRV measurement. The accuracy of within-one-week TTD prediction was 67% for TP and HF power. The accuracy of within-two-week TTD prediction was 82% for TP and 73% for HF. In addition, TTD of the patients was also significantly associated with serum creatinine (r = ?0.42, P = 0.015), serum albumin (r = ?0.46, P = 0.007), and BUN (r = ?0.44, P = 0.010).ConclusionThis is the first study to evaluate the association between cardiovascular autonomic functions and TTD in patients with terminal hepatocellular carcinoma. The inclusion of HRV measurement in prognostic models may improve accuracy in TTD prediction and, hence, facilitate medical decision making in hospice care.     

Association of alpha 2A adrenergic receptor gene (ADRΑ2A) polymorphism with irritable bowel syndrome,microscopic and ulcerative colitis

BackgroundAlpha 2 adrenergic receptors (α2 ARs) play a central role in the regulation of systemic sympathetic activity. Prejunctional alpha 2A adrenoceptor regulates through negative feedback at presynaptic nerve ending. A-1291 C > G polymorphism located in α2-adrenergic receptor gene (ADRΑ2A) has been identified. We investigated the possible association between 1291 C > G polymorphism in the promoter region of ADRΑ2A in clinical subtypes of IBS, ulcerative and microscopic colitis patients.MethodsThis prospective case control study included 92 patients with diarrhea predominant IBS (D-IBS), 44 with constipation predominant IBS (C-IBS), 15 with alternating diarrhea and constipation IBS (M-IBS), 75 ulcerative colitis (UC), 41 microscopic colitis (MC) and 100 healthy controls. The subjects were genotyped by using PCR amplification of the promoter region of ADRΑ2A gene followed by digestion with the restriction enzyme MspI. The study was approved by the institute ethical committee.ResultsA strong genotypic association was observed between α2A-1291 C > G polymorphism and D-IBS (χ² = 6.38, df = 2, p < 0.05). There was no significant difference in α2A-1291 C > G genotype and allele frequency between C-IBS, M-IBS, UC, MC cases and control subjects.ConclusionsA significant association was observed between α2A-1291C > G polymorphism and D-IBS. Thus, α2 AR gene may be a potential candidate involved in the pathophysiology of D-IBS.     

The nitric oxide synthase 3 gene polymorphisms and their association with deep vein thrombosis in Asian Indian patients

BackgroundEndothelium derived nitric oxide is formed from l-arginine by endothelial nitric oxide synthase encoded by the nitric oxide synthase 3 (NOS3) gene. Nitric oxide possesses a variety of protective effects on endothelial cells and therefore NOS3 is a logical candidate gene to be investigated for the susceptibility of deep vein thrombosis (DVT).MethodsOne hundred consecutive patients (M: F = 56:44) with idiopathic deep vein thrombosis and an equal number of age and sex matched healthy controls were the study subjects. All study subjects were typed for five NOS3 polymorphisms (? 786C/T, ? 922A/G, 894G/T, Intron 4 VNTR, and Intron 23 G10T).ResultsTwo polymorphisms (? 922A/G and 894G/T) are showing their association with DVT. ? 922A/G shows both genotypic (P = 0.0218; χ² = 5.25; O.R = 1.94) as well as allelic association (P = 0.0014; χ² = 10.19; O.R = 2.0) while 894G/T shows only allelic (P = 0.04; χ² = 3.93; O.R = 3.93) association with DVT.ConclusionSusceptibility to DVT in North Indian Asian patients may be associated with some variants of NOS3 gene.     

The prognostic value of serum tau in patients with intracerebral hemorrhage

ObjectivesThis study aimed to investigate the relationship between serum tau concentrations and 3-month clinical outcomes in patients with intracerebral hemorrhage.Design and methodsSerum tau concentrations of 176 patients were quantified by enzyme-linked immunosorbent assay. The end points were mortality and poor outcome (modified Rankin Scale score > 2) after 3 months.Results110 patients (62.5%) had a poor outcome at 3 months. The 3-month mortality rate was 36.4% (64/176). A forward stepwise logistic regression selected serum tau concentration as an independent predictor for 3-month mortality (P = 0.002) and poor outcomes (P = 0.009) of patients. A receiver operating characteristic curve analysis showed that serum tau concentration predicted 3-month mortality (P = 0.001) and poor outcomes (P = 0.001) statistically significantly. The area under curve of tau was similar to that of the National Institutes of Health Stroke Scale score for 3-month mortality (P = 0.715) and poor outcomes (P = 0.315). In a combined logistic-regression model, tau statistically significantly improved the area under curve of the National Institutes of Health Stroke Scale score for the prediction of 3-month poor outcome (P = 0.039), but not for the prediction of 3-month mortality (P = 0.106).ConclusionsSerum tau concentration represents a novel biomarker for predicting mortality and poor outcomes at 3 months in patients with intracerebral hemorrhage.     

Associations between genetic polymorphisms of paraoxonase genes and coronary artery disease in a Taiwanese population

ObjectiveWe evaluated the relationship between polymorphisms of the paraoxonase (PON) gene and the risk of coronary artery disease (CAD) in Taiwanese patients.MethodsOur sample set included 369 volunteers, classified into two groups: 162 healthy volunteers and 207 CAD patients aged 60.0 ± 9.7 and 64.3 ± 12.3 years, respectively. Polymorphisms of the PON1 and PON2 genes were determined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) techniques.ResultsThe results indicate that for the PON1 gene, the homozygous genotype RR was found significantly more often among the CAD group compared with the healthy group (OR = 1.965, 95% CI = 1.223–3.159, p = 0.005). Furthermore, for the PON2 gene, the homozygous genotype CC was found significantly more often among the CAD group compared with the control group (OR = 2.525, 95% CI = 1.103–5.780, p = 0.026).ConclusionsIndividuals homozygous for the R allele of the PON1 gene and the C allele of the PON2 gene are more likely to have an increased risk of CAD.     

Serum carotenoids in relation to risk factors for development of atherosclerosis

ObjectiveTo explore associations between serum carotenoids and risk factors for development of atherosclerosis.Design and methodsWe studied 40 early atherosclerosis patients without clinical cardiovascular events and comparable healthy controls aged 45–68 years. Intima-media thickness (IMT) and arterial stiffness were simultaneously measured by carotid ultrasonography, and serum carotenoids and cytokines were determined by high-pressure liquid chromatograph (HPLC) and ELISA kits respectively. We evaluated the associations between serum carotenoids, early atherosclerosis and serum cytokines.ResultsSerum concentrations of lutein and zeaxanthin in early atherosclerosis patients were significantly lower than those of control subjects. PCA logistic analysis found that serum carotenoids were associated with decreased risk of atherosclerosis. In contrast, blood pressure, body mass index and serum triglyceride were positively related to the risk of atherosclerosis. Ridge regression analysis revealed that serum carotenoids were associated with inflammatory cytokines and apoE. More specifically, serum lutein was inversely associated with IL-6 (P < 0.001) and positively associated IFN-γ (P = 0.002). In contrast, zeaxanthin had a significant negative association with VCAM-1 (P = 0.001) and apoE (P = 0.022) .Lycopene was inversely associated with VCAM-1(P = 0.011) and LDL (P = 0.046).ConclusionsThe results suggested that early atherosclerosis patients had lower serum concentrations of lutein and zeaxanthin than healthy subjects. Serum carotenoids were associated with reduced risk of atherosclerosis. The associations between serum carotenoids and inflammatory cytokines may help to explain the possible protective effects of carotenoids on atherosclerosis.     

Prognostic significance of adipocytokines and extracellular matrix activity in heart failure patients with high B-type natriuretic peptide

ObjectivesTo perform risk stratification by serum adipocytokines and serum markers of extracellular matrix in heart failure patients with high b-type natriuretic peptide (BNP).MethodsPatients with heart failure were enrolled in this study. Serum adipocytokines and serum markers of extracellular matrix were analyzed.ResultsIn total, 131 patients were enrolled and followed-up for 240 ± 174 days. Mortality was significantly associated with adiponectin, resistin, type III amioterminal propeptide of procollagen (PIIINP), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase 1 (TIMP-1), and serum creatinine. Heart failure-related admission was significantly associated with apelin, and PIIINP. Cox regression analysis identified that mortality and heart failure-related admissions were significantly associated with MMP-2 (P = 0.008) and PIIINP (P = 0.011), respectively.ConclusionsSerum markers of extracellular matrix rather than adipocytokines may warrant further risk stratification for impacting the prognosis of patients with heart failure with high BNP.