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AIM: To investigate the expression and clinical significance of interferon regulatory factor 4(IRF4)and soluble suppression of tumorigenesis 2(sST2)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: A total of 94 patients with dry eye who admitted to our hospital from January 2019 to December 2021 were selected as the dry eye group, and 97 physical examiners who underwent ophthalmic examination were selected as the control group at the same time. The conjunctival epithelial cells and tears of the subjects were collected, and the clinical indicators, including tear film break-up time(BUT), corneal fluorescein staining(CFS)score, and Schirmer Ⅰ test(SⅠt)were recorded. The levels of IRF4 and sST2 in conjunctival epithelial cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR), and the levels of IRF4 and sST2 in tears were detected by enzyme-linked immunosorbent assay(ELISA). Pearson method was used to analyze the correlation between IRF4 and sST2 levels in conjunctival epithelial cells and tears and clinical indicators of dry eye patients.RESULTS: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears in dry eye group before treatment were significantly higher than those in control group(P<0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients at 4wk after treatment were significantly lower than those before treatment(P<0.001). The BUT and SⅠt of dry eye patients increased significantly at 4wk after treatment, and the CFS score decreased significantly(P<0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients before treatment were positively correlated with CFS score before treatment and negatively correlated with BUT and SⅠt before treatment(P<0.001).CONCLUSION: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of patients with dry eye are increased, and are significantly correlated with BUT, SⅠt and CFS scores, which has potential to become a new therapeutic target for dry eye.
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Context: Interleukin?33 and its receptor soluble suppression of tumorigenicity 2 (sST2) play an important role in inflammation and its role in periodontal disease is yet unclear. The role of both IL?33 and sST2 together in periodontal disease as biomarkers has never been studied. Aim: To assess the levels of IL?33 and sST2 in serum samples of patients with periodontitis and healthy subjects. Methods: A total of 71 subjects (30 healthy subjects and 41 patients with periodontal disease) were included in the cross?sectional study. Community Periodontal Index (CPI) was used to assess periodontal health by utilizing a mouth mirror and a CPI probe. Venous blood was collected and serum was separated. Serum levels of IL?33 and sST2 were determined by the enzyme?linked immunosorbent assay (ELISA) assay. Statistical Analysis: Graph Pad Prism 5 was used for statistical analysis. Mann Whitney test was applied to compare the two groups. Results: The level of IL?33 was not found to be elevated among healthy subjects and sST2 was found elevated among patients with periodontal disease. The serum concentration of IL?33 was found at 472 ± 114 pg/ml and 282 ± 77 pg/ml among healthy subjects and patients with periodontal disease respectively. Significantly higher values of sST2 at 28 ± 2 ng/ml were found among periodontal patients as compared to healthy subjects with values of 18 ± 1 ng/ml. No significant differences were noted between mild to moderate and severe periodontitis for IL?33 and sST2 between the two groups. Conclusion: This study shows alteration in serum levels of IL?33 and sST2 in periodontitis patients. IL?33 and sST2 may be potential inflammatory markers of periodontitis. Further studies are required on a large sample size for better understanding. This pilot study is the first to assess the serum levels of both IL?33 and sST2 together among patients with and without periodontal disease.
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@#Objective To explore the clinical value of soluble suppression of tumorigenesis-2 (sST2) in replacement of N-terminal fragment of the brain natriuretic peptide precursor (NT-proBNP) in cardiac function evaluation in renal failure patients after cardiac surgery. Methods Sixty patients with renal insufficiency after cardiac surgery from January 2019 to June 2019 were divided into a test group, including 34 males and 26 females, with an average age of 49-78 (63.3±4.5) years. Another 60 patients with normal renal function were divided into a control group, including 37 males and 23 females, with an average age of 53-77 (61.7±3.8) years. The perioperative left ventricular ejection fraction, cardiac troponin T, creatine kinase-MB, sST2 and NT-proBNP were compared. Results In patients of the test group, the NT-proBNP level increased significantly during perioperative period, and the change range was different from other cardiac function indexes. The change of sST2 in perioperative period was similar to other cardiac function indexes, which could reflect the change degree of cardiac function after operation. Conclusion sST2 is more important to reflect the change degree of cardiac function in patients with renal dysfunction after cardiac surgery than NT-proBNP.
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BACKGROUND: Liver biopsies have been partially replaced by noninvasive methods for assessing liver fibrosis. We explored the usefulness of four novel biomarkers, enhanced liver fibrosis (ELF), glycosylation isomer of Mac-2 binding protein (M2BPGi), galectin-3, and soluble suppression of tumorigenicity 2 (sST2), in association with liver fibrosis. METHODS: ELF, M2BPGi, galectin-3, and sST2 were assayed in 173 patients with chronic liver diseases. The results were analyzed according to fibrosis grade (F0/1, F2, and F3/4) by transient elastography (TE). RESULTS: ELF, M2BPGi, galectin-3, and sST2 values differed significantly according to TE grade; ELF and M2BPGi values were higher in F2 and F3/4 than in F0/1 (P≤0.001, all), sST2 values were higher in F3/4 than in F0/1 and F2 (P < 0.05), and galectin-3 values were higher in F3/4 than in F0/1 (P=0.0036). ELF and M2BPGi showed good TE fibrosis detection performance (area under the curves [AUC], 0.841 and 0.833 for ≥F2; and 0.837 and 0.808 for ≥F3). The sensitivity and specificity for predicting TE grade F≥2 were 84.1% and 76.7% for ELF and 63.6% and 91.5% for M2BPGi. CONCLUSIONS: This is the first study to compare the liver fibrosis assessment of four novel biomarkers: ELF, M2BPGi, galectin-3, and sST2. The biomarkers varied significantly according to TE grade, and each biomarker showed a different trend. ELF and M2BPGi seem to have comparable good performance for detecting liver fibrosis.
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Humans , Biomarkers , Biopsy , Carrier Proteins , Elasticity Imaging Techniques , Fibrosis , Galectin 3 , Glycosylation , Liver Cirrhosis , Liver Diseases , Liver , Sensitivity and SpecificityABSTRACT
Objective To investigate serum levels of soluble matrix lysin 2 (sST2) in patients with different stages of heart failure and its relationship with prognosis. Methods Data of 300 patients with heart failure of stages A, B, C and D were included in this study. Thirty-three cases of healthy elderly population for physical examination were used as control group. The general information, echocardiography and related biochemical tests containing sST2 and NT-proBNP were collected in the two groups. The survival periods of patients were evaluated according to the Seattle heart failure mode (SHFM). Patients were followed up for 1 year to record the occurrence of adverse events. Results The sST2 level was higher in heart failure group than that of control group. The sST2 level began to increase in stage B, and which increased with the development of cardiac function staging. The sST2 levels were significantly higher in stages B, C and D than those of stage A, and which were significantly higher in stage D than those of stages B and C (P<0.05). There were significantly higher incidence rates of adverse events, left ventricular end diastolic diameter (LVEDD) and left ventricular mass index (LVMI) in the patients with high sST2 level than those of patients with lower sST2 level (P<0.05). Values of sST2, NT-proBNP, LVEDD and LVMI were significantly higher, and values of LVEF and SHFM life expectancy were significantly lower, in patients with adverse events than those of patients without adverse events (P<0.05). There was a negative correlation between sST2 and LVEF, and positive correlation between sST2 with NT-proBNP, LVEDD and LVMI (P<0.05). The size under ROC curve, which was used to predict the cardiovascular endpoint events judged by sST2 was 0.665 (95％CI:0.574-0.757, P<0.01), and the one by NT-proBNP was 0.790 (95％ CI: 0.731-0.848, P<0.01). The best cut-off value of predicting the clinical adverse events was 139.27μg/L by sST2 and 855.35μg/L by NT-proBNP. Conclusion The serum level of sST2 is early indicator of heart failure, which not only reflects the severity of ventricular remodeling but also is one of indicators to estimate the prognosis of heart failure in one year.
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Objective: To preliminarily investigate the relationship between the baseline level of serum soluble ST2 (sST2) and 30-day MACE occurrence rate in patients with ST-elevation myocardial infarction (STEMI). Methods: A total of 121 patients with confirmed diagnosis of STEMI in our hospital from 2015-05-01 to 2015-07-30 were consecutively enrolled. According to baseline sST2 level, the patients were divided into 2 groups:Low sST2 group, the patients with sST2≤56.68 ng/ml, n=61 and High sST2 group, the patients with sST2>56.68 ng/ml, n=60. Clinical condition and 30-day MACE (defined as death and new onset of congestive heart failure) occurrence rate were compared between 2 groups. Results: ① The systolic blood pressure (SBP), Killip class≥II grade, blood levels of cTNI, NT-proBNP, hs-CRP and LVEF were different between 2 groups, all P56.68 ng/ml was the risk factor for 30-day MACE occurrence (HR=1.152, 95%CI 1.078-1.231, P=0.000). Conclusion: Increased baseline level of sST2 implied the higher incidence of death and new onset of congestive heart failure in STEMI patients.
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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 (P35 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.
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Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome/diagnosis , Area Under Curve , Biomarkers/analysis , Chest Pain , Emergency Service, Hospital , Follow-Up Studies , Interleukin-1 Receptor-Like 1 Protein/analysis , Odds Ratio , Prognosis , ROC Curve , Troponin I/analysisABSTRACT
Objective To investigate the predicting value of serum sST2 on risk stratification and prognosis in elderly patients with acute heart failure (AHF).Methods Total of 75 AHF patients aged 60 to 93 were selected in our study who were in Beijing Hospital during 2013.1-2014.8,including 40 cases of male and 35 cases of female.Moreover,38 healthy people aged 70 to 80 were chosen as control group,which contains 18 cases of male and 20 cases of female.Follow-up was performed 1 year after acute attack.We defined the end of observation as recurrence of heart failure or any causes of death.The data was analyzed by SPSS19.0.Results Compared with control group,sST2 level (pg/mL) was significantly elevated in AHF group [(596.9 ±181.2) vs.(1 698.9 ±797.0),P ＜0.001].No significant difference was found between male and female (1 713.1 ± 1 322.2 vs.1 727.5 ±867.1,P =0.956).sST2 level was significantly different between patients with different clinical heart function grade [1 439.5 ±694.5 (mild-Ⅰ and Ⅱ grade) vs.2 057.8 ± 1428.6 (severeⅢ and Ⅳ grade),P =0.026].Among the 75 AHF patients,sST2 level was higher in patients with endpoint events than those without endpoint events [(2 234.4 ± 1 308.5) vs.(1 162.3 ±452.6),P=0.000].According to the independent risk factors of unconditioned logistic bivariate regression model analysis,the levels of sST2,NT-proBNP and the clinical heart function Grade had independent predicting value of AHF (OR value were 1.003,1.001 and 7.46 respectively).We found that the cutoff value of sST2 (1 760 pg/mL) may be an valuable evaluation marker of prognosis,the sensitivity and specificity was 64％ and 92％,and the positive and negtive predictive rate were 89％ and 70％.The accuracy rate was 77％.Combined with NT-proBNP to predict the prognosis of AHF,the result would be more exciting.The area under the ROC curve is 0.889.The endpoint event rate of the patients whose level of sST2 was below 1400pg/mL and NT-proBNP level below 4000pg/mL was 7％,while the data in patients whose level of sST2 is above 1400 pg/mL and NT-proBNP above 4000pg/mL was 95％.Conclusions Early at admission of AHF in elderly patients,sST2 began to elevate markedly related with the extent of heart failure.The result shows that the level of sST2 may be used to evaluate patient.The elevation of sST2 has independent predictive value to the prognosis of AHF.It will be better to predict the prognosis combining ST2 with other biomarkers such as NT-proBNP.
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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.
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Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Biomarkers/blood , Blood Pressure/physiology , C-Reactive Protein/analysis , Calcitonin/blood , Echocardiography, Doppler , Interleukin-1 Receptor-Like 1 Protein/blood , Sepsis/diagnostic imaging , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: Studying the role of soluble ST2 (sST2) during hospitalization for myocardial infarction (MI) can be helpful for predicting the course of the hospitalization and development of complications. METHODS: We included 88 patients with MI (median age, 58 yr). Depending on the course of the hospitalization, the patients were divided into two groups: the favorable (n=58) and unfavorable (n=30) outcome groups. On days 1 and 12 after MI, serum sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by ELISA. RESULTS: On day 1, the concentrations of sST2 and NT-proBNP increased 2.4- and 4.5-fold, compared with the controls. Measurements on day 12 showed a significant decrease in the sST2 level (P=0.001), whereas the NT-proBNP level did not change. On day 1, the sST2 level in the unfavorable outcome group was 2-fold higher than that in the favorable outcome group and 3.7-fold higher than in the controls. On day 12, the marker level decreased in both groups. On day 1, the NT-proBNP level in the unfavorable outcome group was 6.8-fold higher than in the controls and 1.8-fold higher than in the favorable outcome group. On day 12, the level of NT-proBNP remained elevated in both groups. Determining the levels of both sST2 and NT-proBNP increases their diagnostic significance (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.7-3.2; areas under curve [AUC] 0.89; P=0.004). CONCLUSIONS: The level of sST2 is a more sensitive indicator during MI hospitalization than NT-proBNP.
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Female , Humans , Male , Middle Aged , Area Under Curve , Case-Control Studies , Electrocardiography , Enzyme-Linked Immunosorbent Assay , Hospitalization , Logistic Models , Myocardial Infarction/diagnosis , Natriuretic Peptide, Brain/blood , Odds Ratio , Peptide Fragments/blood , Prognosis , Proportional Hazards Models , ROC Curve , Receptors, Somatostatin/bloodABSTRACT
Soluble ST2 ( sST2 ) is protein of interleukin-1 ( IL-1 ) receptor family present in the blood which have been identified has the ability to capture IL-33, thereby inhibiting IL-33/ST2 signaling, the mechanical properties overload of myocardial cells was significantly increased .Thus, when at the onset of heart failure or chronic heart failure deteriorated , or at scarring resulted by myocardial infarction , soluble ST2 can be detected in the blood .The purpose of this review is to discuss the role of soluble ST 2 ( sST2) as a new cardiovascular marker.
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The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 +/- 464.0 pg/mL) than in healthy controls (96.0 +/- 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1beta (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.
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Adult , Aged , Female , Humans , Male , Middle Aged , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/blood , C-Reactive Protein/analysis , Interleukin-1beta/analysis , Interleukin-6/analysis , Interleukins/analysis , Osteoarthritis/blood , Receptors, Cell Surface/analysis , Synovial Fluid/metabolismABSTRACT
<p><b>OBJECTIVE</b>The purpose of the present study was to investigate the relation between the dose of tumor cell inoculation (especially the doses less than minimum required to evoke tumor growth) and the anti-tumor immune system, particularly lymphoblast formation and cytotoxic activity of lymphcytes.</p><p><b>METHOD</b>We inoculated rats with various doses of SST-2 tumor cells and examined natural killer (NK) cell activity and lymphoblast formationin vitro.</p><p><b>RESULT</b>The results showed that the cytotoxicities against SST-2 cells and lymphoblast formation of lymphocytes were enhanced by small dose inoculation of tumor cells that could not induce tumor growth.</p><p><b>CONCLUSION</b>It was suggested that was lymphocutes play an important role as an anti-tumor immune system at small doses of tumor inoculation, which appears to reflect an early stage of tumor growthin vivo. It was also suggested that SST-2 tumor inoculation might be a useful model for studying the anti-tumor immune response in SHR rats.</p>
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Objective: The purpose of the present study was to investigate the relation between the dose of tumor cell inoculation (especially the doses less than minimum required to evoke tumor growth) and the anti-tumor immune system, particularly lymphoblast formation and cytotoxic activity of lymphcytes. Method: We inoculated rats with various doses of SST-2 tumor cells and examined natural killer (NK) cell activity and lymphoblast formation in vitro. Result: The results showed that the cytotoxicities against SST-2 cells and lymphoblast formation of lymphocytes were enhanced by small dose inoculation of tumor cells that could not induce tumor growth. Conclusion: It was suggested that was lymphocutes play an important role as an anti-tumor immune system at small doses of tumor inoculation, which appears to reflect an early stage of tumor growth in vivo. It was also suggested that SST-2 tumor inoculation might be a useful model for studying the anti-tumor immune response in SHR rats.