BACKGROUNDMany studies have explored the diagnostic performance of soluble suppression of tumorigenicity-2 (sST2) for heart failure (HF), but the results are inconsistent. Here, we performed a meta-analysis to assess the role of sST2 in the diagnosis of HF.

METHODSWe searched PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database from inception to April 2015. Studies that investigated the diagnostic role of sST2 for HF were reviewed. The numbers of true-positive, false-positive, false-negative, and true-negative results were extracted to calculate pooled diagnostic odds ratio (DOR) with 95% confidence interval (CI) and the summary receiver operating characteristic curve and area under the curve (AUC). The Spearman correlation coefficient was used to check the threshold effect. The Cochran Q statistic (P < 0.05) and the inconsistency index (I2 > 50%) were used to assess the nonthreshold effect. Meta-regression was conducted to explore the source of heterogeneity; subgroup analysis showed the results in different subgroups. Finally, the Deeks' test was performed to assess the publication bias.

RESULTSNine articles including 10 studies were included in the meta-analysis. The pooled sensitivity was 0.84 (95% CI: 0.81-0.86), and pooled specificity was 0.74 (95% CI: 0.72-0.76). The summary DOR was 8.49 (95% CI: 4.54-15.86), and AUC was 0.81 (standard error: 0.03). The Spearman correlation coefficient identified the nonsignificant threshold effect (coefficient = 0.49, P = 0.148), but the nonthreshold effect heterogeneity was significant (Cochran Q = 58.52, P < 0.0001; I2 = 84.6%). Meta-regression found that characteristics of controls might be the suggestive source of nonthreshold effect heterogeneity (P = 0.095). Subgroup analysis found that DOR was 5.65 and 7.86, respectively for the controls of hospital patients and healthy populations. Deeks' test demonstrated that there was no publication bias (P = 0.616).

CONCLUSIONThe meta-analysis illustrated that sST2 might play a role in diagnosing HF.

Aged ; Female ; Heart Failure ; diagnosis ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; physiology ; Male ; Middle Aged ; Publication Bias

Objective: To investigate the distribution characteristics of LymphGen genotyping in a diffuse large B-cell lymphoma (DLBCL) population and verify its prognostic value. Methods: We collected the clinical data and paraffin-embedded tumor tissue samples of 155 patients with newly diagnosed DLBCL in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. DNA was extracted from tumor tissue and 475 gene mutations were detected by next-generation sequencing technology. We investigated the distribution of LymphGen genotyping in the DLBCL population, patients with different COO genotypes in the Xinjiang region, and their effects on PFS and OS. Results: ①Among 155 patients, 105 patients (67.7%) could be genotyped, including 14 (9.0%) for MCD, 26 (16.8%) for BN2, 10 (6.5%) for N1, 8 (5.2%) for EZB, 27 (17.4%) for A53, and 20 (12.9%) for ST2. ②The distribution of each gene subtype was different in different cell origin (COO) types (P=0.021) . ST2 was dominant in the germinal center type (GCB) group (28.8%) , and A53 and MCD were dominant in the non-GCB group (35.8%, 17.0%) . The BN2 type was the most common in both groups (23.1%, 26.4%) . ③There were statistically significant differences in progression-free survival (PFS) and overall survival (OS) among different gene subtypes (P=0.031 and 0.005, respectively) . N1 and A53 had poor prognosis. The 2-year PFS and OS rates of N1 were both (21.3±18.4) %, and the 3-year PFS and OS rates of A53 were (60.9±11.3) %, (46.8±10.9) %, respectively. ④ The 3-year PFS and OS rates of MCD were the best, but the 5-year PFS and OS rates were worse. ⑤In the ROC curve of LymphGen genotyping for OS prediction, the AUC was 0.66, showing a certain degree of differentiation. Conclusion: LymphGen genotyping in the DLBCL population was different from previous reports and was of great significance for the prognosis of patients with DLBCL.
Antineoplastic Combined Chemotherapy Protocols ; Disease-Free Survival ; Genotype ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prognosis ; Retrospective Studies

This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction (MI) in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients (MI group) and 929 normal subjects (NC group). Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms (SNPs) in the genes encoding IL-33, ST2, and IL-1RaP (rs11792633, rs1041973 and rs4624606). The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0.031, 0.647, 0.322 in MI group and 0.026, 0.712, 0.263 in NC group, and the allele frequencies of A and T were 0.192, 0.808 in MI group and 0.157, 0.843 in NC group. There were significant differences in rs4624606 genotypes and allele frequencies between MI group and NC group (P<0.05). For rs11792633, the allele frequencies of C and T were 0.45, 0.55 in MI group and 0.454, 0.546 in NC group with no significant differences found between the two groups. Compared with genotype CC+TC, rs11792633 genotype TT had an increased risk of hypertension (P<0.05). However, there were no significant differences in the frequencies of rs11792633 genotypes between the two groups. No significant differences were noted in the frequencies of rs1041973 genotype and allele between the two groups. Logistic regression analysis showed that rs4624606 genotypes AT and AA+AT were both significantly associated with MI (AT: OR=1.325, P=0.029, 95% CI=1.03-1.705; AA+AT: OR=1.316, P=0.028, 95% CI=1.03-1.681) after factors such as age, gender, smoking, drinking, body mass index (BMI), triglyceride (TG) and cholesterol were adjusted. Those carrying rs4624606 genotype AT or AA+AT had an increased risk of MI. No associations were found between the polymorphisms of the other two loci with MI. It was concluded that, in the IL33/ST2 signal pathway, the A allele of rs4624606 polymorphism of IL-1RaP gene is a potential independent risk factor for MI, and the genotypes AA+AT and AT are associated with the incidence of MI.
China ; Ethnic Groups ; genetics ; Female ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; Interleukin-33 ; Interleukins ; genetics ; metabolism ; Male ; Myocardial Infarction ; genetics ; Receptors, Cell Surface ; genetics ; metabolism ; Signal Transduction ; genetics

BACKGROUNDAcute myocardial infarction (AMI) is a common cardiac emergency with high mortality. Serum soluble ST2 (sST2) is a new emerging biomarker of cardiac diseases. The present study is to investigate the predictive value of sST2 and interleukin-33 (IL-33) for risk stratification and prognosis in patients with AMI.

METHODSFifty-nine patients with AMI, whose chief complaint was chest pain or dyspnea, were selected for our study. Physical examination, chest radiograph, electrocardiograph (ECG), biomarkers of myocardial infarction, NT-proBNP, echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI. Thirty-six healthy people were chosen as the control group. Serum samples from these subjects (patients within 24 hours after acute attack) were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay (ELISA) kit. The follow-up was performed on the 7th day, 28th day, 3rd month and 6th month after acute attack. According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.

RESULTSMedian sST2 level of the control group was 9.38 ng/ml and that of AMI patients was 29.06 ng/ml. Compared with the control group, sST2 expression in the AMI group was significantly different (P < 0.001). In contrast, the IL-33 level showed no significant difference between the two groups. Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score. IL-33 had no relationship to recurrence of AMI. Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.

CONCLUSIONSEarly in the course (<24 hours) of AMI, sST2 usually increases markedly. The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score. The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients. However, there is no significant relationship between IL-33 and the prognosis of AMI patients.

Acute Disease ; Biomarkers ; blood ; Female ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; Interleukin-33 ; Interleukins ; blood ; Male ; Myocardial Infarction ; blood ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Prognosis ; Receptors, Cell Surface ; blood ; Risk

OBJECTIVE: To investigate the expression and role of Interleukin-33 (IL-33) and ST2 in the nasal polyps of human Eosinophilic and non-Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS and non-ECRS). METHOD: IL-33 and ST2 protein expression in nasal polyps of ECRS and non-ECRS as well as in seemingly normal mucosa of the inferior turbinate tissue was investigated by immunohistochemical staining and messenger RNA (mRNA) expression of IL-33 and ST2 was assessed by realtime polymerase chain reaction (PCR) in 27 subjects with ECRS, 33 subjects with non-ECRS, and 11 control subjects. RESULT: (1) The ST2 was found both in nasal polyps of ECRS and non-ECRS,especially in ECRS, yet hardly found in the normal mucosa of the inferior turbinate tissue; (2) The expression of ST2 mRNA in nasal polyps of ECRS was higher than that in non-ECRS and normal inferior turbinate tissue, and the difference was both prominent in statistics (P<0.01); (3) The expression patterns of IL-33 at both mRNA and protein levels were not significantly different among the three groups (P>0.05). CONCLUSION The IL-33 and its receptor ST2 were both expressed in human nasal polyps including ECRS and non-ECRS, meanwhile the expression patterns of ST2 at both mRNA and protein levels were significantly higher in nasal polyps of ECRS. The current study suggests that IL-33 and its receptor ST2 may play important roles in the pathogenesis of chronic rhinosinusitis with nasal polyps, especially in ECRS through the increased expression of ST2 in Eosinophils as a hypothesis.
Chronic Disease ; Eosinophils ; immunology ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; Interleukin-33 ; metabolism ; Nasal Mucosa ; metabolism ; Nasal Polyps ; immunology ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface ; metabolism ; Rhinitis ; immunology ; Sinusitis ; immunology ; Turbinates ; metabolism

Soluble suppression of tumorigenicity 2 (sST2) has emerged as a biomarker of cardiac stretch or remodeling, and has demonstrated a role in acutely decompensated heart failure. However, its role in sepsis-induced cardiac dysfunction is still unknown. We explored whether sST2 serum concentration reflects either systolic or diastolic dysfunction as measured by Doppler echocardiography. In a total of 127 patients with sepsis, correlations between sST2 and blood pressure, left ventricular (LV) ejection fraction, LV diastolic filling (ratio of early transmitral flow velocity to early diastolic mitral annulus velocity), and resting pulmonary arterial pressure were evaluated. Correlations between sST2 and other sepsis biomarkers (high-sensitivity C-reactive protein [hs-CRP] and procalcitonin) were also examined. sST2 showed a moderate correlation with mean arterial pressure (r=-0.3499) but no correlation with LV ejection fraction, diastolic filling, or resting pulmonary hypertension. It showed moderate correlations with hs-CRP and procalcitonin (r=0.2608 and r=0.3829, respectively). sST2 might have a role as a biomarker of shock or inflammation, but it cannot reflect echocardiographic findings of LV ejection fraction or diastolic filling in sepsis.
Aged ; Aged, 80 and over ; Biomarkers/blood ; Blood Pressure/physiology ; C-Reactive Protein/analysis ; Calcitonin/blood ; Echocardiography, Doppler ; Female ; Humans ; Interleukin-1 Receptor-Like 1 Protein/*blood ; Male ; Middle Aged ; Sepsis/diagnostic imaging/metabolism/*physiopathology ; Ventricular Function, Left/physiology

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. METHODS: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. RESULTS: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P<0.0001). In all patients, the sST2 level at arrival showed higher independent predictive power than hs-cTnI (odds ratio [OR] 20.13, P<0.0001 and OR 2.61, P<0.0008, respectively). sST2 at ED arrival showed a greater prognostic value for cardiovascular events in STEMI (area under the curve [AUC] 0.80, P<0.001) than NSTEMI patients (AUC 0.72, P<0.05). Overall, 51% of the STEMI patients with an sST2 value>35 ng/mL at ED arrival died during the 30-day follow-up. CONCLUSIONS: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality.
Acute Coronary Syndrome/diagnosis/*mortality ; Aged ; Area Under Curve ; Biomarkers/analysis ; Chest Pain ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Humans ; Interleukin-1 Receptor-Like 1 Protein/*analysis ; Male ; Middle Aged ; Odds Ratio ; Prognosis ; ROC Curve ; Troponin I/*analysis

BackgroundSerum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown.

MethodsA total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI.

ResultsBaseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = -0.243, P = 0.009) and LV ejection fraction (r = -0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201-8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084-3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI.

ConclusionsHigh baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology.

Adrenergic beta-Antagonists ; administration & dosage ; therapeutic use ; Adult ; Aged ; Biomarkers ; blood ; Female ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; blood ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; ST Elevation Myocardial Infarction ; blood ; drug therapy ; pathology

PURPOSE: IGFBP-3 leads to the induction of insulin resistance in 3T3-L1 adipocytes. We carried out a series of experiments to elucidate the effects of IGFBP-3 on adipokines and gene expressions. METHODS: We treated fully-differentiated 3T3-L1 adipocytes with IGFBP-3 (0.5, 1, and 2 microg/mL) for one day and measured the mRNA levels of adiponectin, leptin, resistin, and TNF-alpha by RT-PCR, and adiponectin, leptin, resistin, and IL-6 protein levels in the culture supernatant were measured using multiplex adipokine assay ELISA Kits (Linco Research, St. Charles, Missouri). Gene expression in 3T3-L1 adipocyte cells using a microarray method was performed. RESULTS: IGFBP-3 inhibited the expression of adiponectin, leptin, resistin, and TNF-alpha mRNA. IGFBP-3 at 0.5 and 1 micro/mL decreased adiponectin release, but IL-6 release was increased at 2 micro/mL IGFBP-3. A dose-dependent inhibition of leptin was released by IGFBP-3 at 50%. Resistin release was decreased by 40%. The effect of IGFBP-3 on the gene expression in 3T3-L1 adipocyte cells using a microarray assay related to an increase of agouti-realted proteins (Agrp) and Janus kinase 2 (JAK2), and a decrease of the ras homolog gene family (Rhoq), acyl-CoA synthetase long-chain family member 6 (Acsl6), and the interleukin-1 receptor-associated kinase 1 (Irak1). CONCLUSION: IGFBP-3 regulates several adipokines gene expressions that are known to modulate insulin sensitivity, and this regulation may be attributable to the insulin resistance effect of IGFBP-3 on adipocytes.
Adipocytes ; Adipokines ; Adiponectin ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Humans ; Insulin Resistance ; Insulin-Like Growth Factor Binding Protein 3 ; Interleukin-1 Receptor-Associated Kinases ; Interleukin-6 ; Janus Kinase 2 ; Leptin ; Ligases ; Proteins ; Resistin ; RNA, Messenger ; Tumor Necrosis Factor-alpha

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.
Bacteriophages ; Drug Evaluation, Preclinical ; Genes, Reporter ; HEK293 Cells ; Humans ; Interleukin-6 ; metabolism ; Lipopolysaccharide Receptors ; metabolism ; Luciferases ; genetics ; metabolism ; Peptide Library ; Peptides ; metabolism ; pharmacology ; Promoter Regions, Genetic ; Protein Binding ; Signal Transduction ; drug effects ; Toll-Like Receptor 1 ; metabolism ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 6 ; metabolism ; Transfection ; Tumor Necrosis Factor-alpha ; metabolism