BACKGROUND: Amino-terminal pro-B type natriuretic peptide (NT-proBNP) is a well-established prognostic factor in heart failure (HF). However, numerous causes may lead to elevations in NT-proBNP, and thus, an increased NT-proBNP level alone is not sufficient to predict outcome. The aim of this study was to evaluate the utility of two acute response markers, high sensitivity C-reactive protein (hsCRP) and heart-type fatty acid binding protein (H-FABP), in patients with an increased NT-proBNP level. METHODS: The 278 patients were classified into three groups by etiology: 1) acute coronary syndrome (ACS) (n=62), 2) non-ACS cardiac disease (n=156), and 3) infectious disease (n=60). Survival was determined on day 1, 7, 14, 21, 28, 60, 90, 120, and 150 after enrollment. RESULTS: H-FABP (P<0.001), NT-proBNP (P=0.006), hsCRP (P<0.001) levels, and survival (P<0.001) were significantly different in the three disease groups. Patients were divided into three classes by using receiver operating characteristic curves for NT-proBNP, H-FABP, and hsCRP. Patients with elevated NT-proBNP (≥3,856 pg/mL) and H-FABP (≥8.8 ng/mL) levels were associated with higher hazard ratio for mortality (5.15 in NT-proBNP and 3.25 in H-FABP). Area under the receiver operating characteristic curve analysis showed H-FABP was a better predictor of 60-day mortality than NT-proBNP. CONCLUSIONS: The combined measurement of H-FABP with NT-proBNP provides a highly reliable means of short-term mortality prediction for patients hospitalized for ACS, non-ACS cardiac disease, or infectious disease.
Acute Coronary Syndrome/blood/*diagnosis/mortality ; Aged ; Area Under Curve ; Biomarkers/blood ; C-Reactive Protein/*analysis ; Fatty Acid-Binding Proteins/*blood ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*blood ; Peptide Fragments/*blood ; Prognosis ; Proportional Hazards Models ; ROC Curve

PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
Blotting, Western ; Caffeic Acids ; Cell Line, Tumor ; Cell Proliferation ; DNA, Bacterial/analysis/genetics ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/*metabolism ; Gastric Mucosa/*metabolism/pathology ; Gastritis/pathology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/metabolism/pathology/physiopathology ; Helicobacter pylori/pathogenicity/physiology ; Humans ; NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism ; Peptide Fragments ; Phenylethyl Alcohol/analogs & derivatives ; Proto-Oncogene Proteins c-jun ; Repressor Proteins ; Transcription Factor AP-1/*biosynthesis ; Transcription Factors/*metabolism ; beta Catenin/*metabolism

OBJECTIVE: Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: Fifty-nine patients with DCM (mean age, 55 +/- 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. RESULTS: The mean LV ejection fraction was 24 +/- 9% and the post-T1 value was 254.5 +/- 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (beta = -0.351, p = 0.016) and the LV mass/volume ratio (beta = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (beta = -0.339, p = 0.017). CONCLUSION: Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.
Adult ; Aged ; Algorithms ; Blood Pressure ; Cardiomyopathy, Dilated/*diagnosis/radiography ; Echocardiography ; Extracellular Space/physiology/*radiography ; Female ; Heart Ventricles/physiopathology/radiography ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Natriuretic Peptide, Brain/analysis ; Peptide Fragments/analysis ; *Ventricular Remodeling

OBJECTIVETo investigate the effect of Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood on the reproductive endocrine-immune network and its mechanisms in patients with primary Sjogren's syndrome (pSS).

METHODSSeventy pSS patients were randomly assigned to two groups using a randomized digital table: the integrative therapy group (36 cases) and the control group (34 cases). Thirty healthy subjects were taken as a normal group. The control group was treated with hydroxychloroquine sulfate tablets alone, and the integrative therapy group was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with hydroxychloroquine sulfate tablets. The treatment course was 6 months for both groups. Before and after treatment, serum estradiol (E2), testosterone (T), luteinizing hormone (LH), prolactin (PRL) by radioimmunoassay and immunoglobulin (IgG) by immunodiffusion, erythrocyte sedimentation rate (ESR) by Westergren, interferon-γ (IFN-γ) and interleukin-4 (IL-4) by enzyme linked immunosorbent assay were determined.

RESULTSE2 and T levels in all patients were lower than those of normal subjects before treatment (P<0.05) and were increased significantly after 6-month treatment (P<0.05). ESR, FSH, LH, IgG, IFN - γ, IL - 4 and ratios of E2/T, and IFN -γ/IL in the patients were higher than those of normal subjects before the treatments (P<0.05), and were reduced significantly after the treatments (P<0.05). The T and IFN - γ levels and E2/T ratio in the patients treated with integrative therapy were reduced significantly compared with the control group (P<0.05). However, the PRL levels before and after treatment were not significantly changed in the two groups (P>0.05). The ratios of E2/T and IFN -γ/IL-4, and levels of IgG and ESR were positively correlated before and after treatment (P<0.05).

CONCLUSIONSThe ratios of E2/T and IFN -γ/IL-4 might be used as indicators of pSS activity. Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with Western medicine could improve the therapeutic effect by regulating the reproductive endocrine-immune network in pSS patients.

Adult ; Blood Sedimentation ; Drugs, Chinese Herbal ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Estradiol ; blood ; Female ; Humans ; Hydroxychloroquine ; administration & dosage ; therapeutic use ; Immunodiffusion ; Immunoglobulins ; blood ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Luteinizing Hormone ; blood ; Male ; Peptide Fragments ; analysis ; Prolactin ; blood ; Radioimmunoassay ; Random Allocation ; Sjogren's Syndrome ; drug therapy ; Tablets ; Testosterone ; blood

BACKGROUNDN-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury. However, it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population.

METHODSIn a community based study, levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years. The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml. The association of hs-cTnT levels and NT-proBNP levels was analyzed.

RESULTSWhen the subjects with undetectable (<0.003 ng/ml), intermediate (0.003-0.014 ng/ml), and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r = 0.175, P < 0.001), a strong association between the hs-cTnT levels and NT-proBNP levels was observed (β = -0.206, P < 0.001; β = -0.118, P < 0.001, respectively). In multivariable analyses, older age and hs-cTnT were positively and independently associated with NT-proBNP levels (β = 0.341, P < 0.001; β = 0.143, P < 0.001, respectively), and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels. When the subjects with normal or elevated NT-proBNP were analyzed separately, the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group, whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (β = 0.399, P < 0.01).

CONCLUSIONSIn this community based population, NT-proBNP elevation was common. In addition to female gender and older age, subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.

Biomarkers ; analysis ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Troponin T ; blood

China ; Female ; Heart Failure ; diagnosis ; drug therapy ; metabolism ; Humans ; Male ; Natriuretic Peptide, Brain ; analysis ; Peptide Fragments ; analysis

OBJECTIVETo study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF.

METHODSMyocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed.

RESULTSCompared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01).

CONCLUSIONSUpregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.

Acetylation ; E1A-Associated p300 Protein ; genetics ; Female ; Histone Acetyltransferases ; genetics ; Histone Deacetylases ; genetics ; Histones ; metabolism ; Humans ; Infant ; Male ; Myocardium ; metabolism ; Peptide Fragments ; genetics ; RNA, Messenger ; analysis ; Sialoglycoproteins ; genetics ; Tetralogy of Fallot ; metabolism

Effective biomarkers for clinical usage of osteoarthritis are still limited. It was confirmed that C-terminal crosslinking telopeptide of type I collagen (CTX- II) was a specific marker reflecting degradation of articular cartilage. Detection of CTX- II could promptly reflect level of cartilage injury and degradation ,diagnose OA,predict its progress,monitor effects of drug treatment, thus, reflect the condition of osteoarthritis patient indirectly. Application of CTX- II focused mainly on in the early stage of OA and need together to detect with other biomarkers,in order to more accurately reflection of the pathological changes of OA,but the specific clinical significance of CTX- II results still need to improve further.
Biomarkers ; analysis ; Cartilage, Articular ; pathology ; Collagen Type II ; analysis ; Early Diagnosis ; Humans ; Osteoarthritis ; diagnosis ; Peptide Fragments ; analysis

BACKGROUND/AIMS: Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery. METHODS: Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (> or = 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI. RESULTS: A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NT-proBNP level of > 302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p < 0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI. CONCLUSIONS: Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.
Aged ; Biological Markers/blood ; Chi-Square Distribution ; Female ; Heart Diseases/blood/*etiology/mortality ; Heart Failure/etiology ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/etiology ; Natriuretic Peptide, Brain/*blood ; Odds Ratio ; Peptide Fragments/*blood ; Predictive Value of Tests ; Preoperative Period ; Prospective Studies ; ROC Curve ; Risk Assessment ; Risk Factors ; Sensitivity and Specificity ; Surgical Procedures, Elective ; Time Factors ; Tomography, Emission-Computed, Single-Photon ; Treatment Outcome ; Vascular Diseases/blood/mortality/radionuclide imaging/*surgery ; Vascular Surgical Procedures/*adverse effects/mortality

Alzheimer's disease (AD), also called presenile dementia, is one of the most common neurodegenerative diseases in elderly people. The main pathological features of AD include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuron loss. A biomarker is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Class biomarkers of AD such as Abeta and phosphorylated tau have been widely used in clinical diagnosis of AD patients. Recently, novel technologies like proteomics, genomics, and imaging techniques have expanded the role of a biomarker from early diagnosis to monitoring the progression of diseases and evaluating the response to various treatments. In this article, we will review the progress of various biomarkers of AD.
Adipokines ; cerebrospinal fluid ; Alzheimer Disease ; cerebrospinal fluid ; diagnosis ; diagnostic imaging ; metabolism ; Amyloid beta-Peptides ; cerebrospinal fluid ; Biomarkers ; analysis ; Chitinase-3-Like Protein 1 ; Fluorodeoxyglucose F18 ; Humans ; Lectins ; cerebrospinal fluid ; Peptide Fragments ; cerebrospinal fluid ; Phosphorylation ; Positron-Emission Tomography ; Presenilins ; analysis ; alpha 1-Antitrypsin ; blood ; tau Proteins ; cerebrospinal fluid