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MicroRNA-20a-5p (miR-20a-5p) has been shown to function as a tumor promoter factor in several cancers. However, its role in small cell lung cancer (SCLC) remains unclear. In this study, we have made an attempt to measure the tumor tissue levels of miR-20a-5p in patients with SCLC using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The biological function of miR-20a-5p in SCLC cells was investigated in vitro and in vivo studies, including cell proliferation, migration assays and tumorigenicity in nude mice. Meanwhile?we conducted the luciferase reporter assay to verify the biological relationship between miR-20a-5p and CCNG2. The expression of miR-20a-5p was significantly upregulated in human SCLC compared to that in normal tissues. Kaplan-Meier analysis indicated that patients with high expression of miR-20a-5p are closely related with the shorter survival of SCLC. Further, multivariate analysis showed that miR-20a-5p was an independent prognostic factor. Increasing miR-20a-5p expression promotes the proliferation, migration and invasion of the NCI-H446 cells in vitro and in vivo. Dual-luciferase reporter gene assay demonstrated that miR-20a-5p directly targets CCNG2. These findings suggest that miR-20a-5p levels might be a novel diagnostic and prognostic marker of SCLC. Inhibiting miR-20a-5p could be a promising therapeutic strategy for SCLC.
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Objective: The aim of the present study was to find a correlation of serum Suppression of tumorigenicity 2 (ST2) levels with severity of diastolic dysfunction on echocardiography and cardiac magnetic resonance imaging (CMRI) in heart failure with preserved ejection fraction (HFpEF) patients. Methods: Fifty patients aged _x0001_18 years fulfilling diagnostic criteria for HFpEF were included. ST2 levels, 2D echocardiography and CMRI were performed. Left ventricular ejection fraction, E/A, Septal E/E’, left atrial volume index (LAVI), tricuspid regurgitation (TR), assessment of diastolic dysfunction, T1 mapping in milliseconds and late gadolinium enhancement (LGE) in percentage were noted. The primary outcome measure was to study correlation of ST2 levels with severity of diastolic dysfunction, whereas the secondary outcome measures were to study correlation of ST2 levels with native T1 mapping and LGE on CMRI. Results: ST2 levels showed statistically significant and positive correlation with E/E’ (r ¼ 0.837), peak TR velocity (r ¼ 0.373), LAVI (r ¼ 0.74), E/A (r ¼ 0.420), and T1 values in milliseconds (r ¼ 0.619). There was no statistically significant correlation between ST2 level and LGE in % (r ¼ 0.145). The median ST2 levels in patients with E/E’ > 14 and E/E’ 14 were 110.8 and 36.1 respectively (p-value < 0.05). The mean ST2 levels were significantly higher in patients who had diastolic dysfunction grade III (126.4) and New York Heart Association class IV (133.3). Conclusions: Evaluation of ST2 adds important information to support the diagnosis of left ventricular diastolic dysfunction in patients with HFpEF
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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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ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.
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Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family which plays roles in the nucleus as a nuclear factor and is released by damaged or necrotic cells to act as a cytokine. It can be released via damaged or necrotic cells and functions as a cytokine. The released IL-33 activates the downstream NF-κB and MAPKs signaling pathways through the isomers of the specific receptor ST2 and the interleukin-1 receptor accessory protein (IL-1RAcP), resulting in danger signals and the activated multiple immune responses. IL-33 is abnormally expressed in various tumors and involves in tumorigenesis, development, and metastasis. Moreover, IL-33 can play both pro-tumor and anti-tumor roles in the same type of tumor.
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Humans , Cytokines , Interleukin-33/genetics , MAP Kinase Signaling System , NF-kappa B/metabolism , NeoplasmsABSTRACT
Objective:To explore the application value of soluble tumor suppressor 2 (SST2), galectin-3 combined with magnetic resonance multimodality in the diagnosis of myocardial fibrosis.Methods:The clinical data of 88 patients with cardiomyopathy from January 2017 to December 2019 in Handan Central Hospital of Hebei Province were retrospectively analyzed as the experimental group, and 100 healthy people in the same period were selected as the control group. According to the results of cardiac magnetic resonance imaging (CMRI)-late gadolinium enhanced (LGE), the patients with cardiomyopathy were divided into LGE positive and LGE negative. The arrhythmia rate was evaluated by ambulatory electrocardiogram. The New York Heart Association (NYHA) cardiac function grade was recorded. The left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were detected by echocardiography. The SST2, galectin-3 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of SST2 and Galectin-3 in predicting myocardial fibrosis in patients with cardiomyopathy.Results:CMRI-LGE results of 88 patients with cardiomyopathy showed that LGE was positive in 42 cases and negative in 46 cases. The arrhythmia rate, LVEDD, SST2 and galectin-3 in experimental group were significantly higher than those in control group: 67.05% (59/88) vs. 2.00% (2/100), (46.55 ± 5.99) mm vs. (27.92 ± 2.05) mm, (61.83 ± 10.57) μg/L vs. (24.99 ± 7.69) μg/L and (18.65 ± 3.39) μg/L vs. (7.12 ± 1.33) μg/L, the LVEF was significantly lower than that in control group: (55.11 ± 8.36)% vs. (68.83 ± 9.45)%, and there were statistical differences ( P<0.01). The arrhythmia rate, NYHA cardiac function grade, LVEDD, SST2 and galectin-3 in patients with LGE positive were significantly higher than those in patients with LGE negative: 88.10% (37/42) vs. 47.83% (22/46), (3.10 ± 0.53) grade vs. (2.11 ± 0.61) grade, (48.88 ± 5.95) mm vs. (44.41 ± 5.24) mm, (65.58 ± 11.73) μg/L vs. (58.40 ± 8.10) μg/L and (21.00 ± 2.72) μg/L vs. (16.51 ± 2.39) μg/L, the LVEF was significantly lower than that in patients with LGE negative: (52.15 ± 8.23)% vs. (57.82 ± 7.60)%, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the optimal critical values of serum SST2 and galectin-3 for predicting myocardial fibrosis in patients with cardiomyopathy were 65.07 μg/L and 18.46 μg/L, the area under the curve was 0.714 (95% CI 0.604 to 0.825, P = 0.001) and 0.894 (95% CI 0.828 to 0.960, P = 0.001), the sensitivity was 61.9% and 85.7%, and the specificity was 80.4% and 82.6%. Conclusions:Magnetic resonance multimodality has a good ability in detecting myocardial fibrosis, and serum SST2 and galectin-3 have good predictive value for myocardial fibrosis. SST2 and galectin-3 combined with magnetic resonance multimodality has important clinical significance in the diagnosis of myocardial fibrosis.
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Aim To study the expression pattern of neuroblastoma, suppression of tumorigenicity 1 (NBL1) in pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Methods Forty rats were randomly allocated into control group (n = 10) and MCT group (n= 30). Intraperitoneal injection of 60mg 'kg"1 MCT for MCT group or equal volume normal saline for control group was performed. The changes of NBL1 in lungs and plasma of the 3 rd, 4 th and 5 th week after MCT injection were detected respectively. NBL1 levels in rat plasma were detected by enzyme linked immunosorbent assay. Results At the 3 rd, 4 th, and 5 th week after MCT injection, the mRNA level of NBL1 decreased by 70%, 81% and 89% , the protein level decreased by 36% , 78% and 99% , and the plasma concentration of NBL1 decreased from (2. 82 ± 0. 58) xg L"1 (control rats) to (1. 90±0.55) fig L-1, (1.51 ±0.43) jxg L'1, (0.64 ±0. 34)ug L-l and presented a negative correlation with pulmonary hemodynamic indices and right ventricular hypertrophy. Immunohistochernical staining demonstrated that NBL1 was mainly expressed in small pulmonary arteries in normal lungs from control group but seldom detected in severely remodeled pulmonary arteries from MCT group. Furthermore, NBL1 significantly inhibited the activation of BMP signal in pulmonary artery endothelial cells induced by BMP2/4. Conclusions NBL1 level demonstrates a stepwise decrease in MCT induced PAH, implying its vital roles in the pulmonary vascular remodeling process and the possibility of NBL1 to be a potential biomarker for PAH.
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Objective@#To determine the level of Soluble Suppression of Tumorigenicity-2 (sST2) in patients with heart failure(HF) and atrial fibrillation (AF), and to explore its diagnostic and prognostic value in patients with HF and AF.@*Methods@#A prospective cohort study was carried out to investigate the data of 185 HF patients who were hospitalized between January 2018 and June 2018 in department of cardiology or department of cardiac care unit in TEDA International Cardiovascular Hospital. And according to whether they had atrial fibrillation before admission, we categorized patients into: HF with sinus rhythm (HF-SR, n=90) and HF with AF(HF-AF, n=95). Meanwhile, 40 healthy controls were collected. Baseline data of HF-SR and HF-AF groups and plasma sST2 levels in different ejection fraction groups were compared. Plasma sST2 level was determined by enzyme-linked immunosorbent assay(ELISA). Statistical methods such as nonparametric test and Spearman correlation analysis were used. The receiver operating characteristic curve was applied to evaluate the diagnostic value of sST2 in HF-SR and HF-AF groups. And by using the COX risk model, Multi-factor COX analysis was used to analyze the prognosis of patients.@*Results@#Compared with healthy controls, the median (P25, P75) of Plasma sST2 levels in HF patients increased remarkably [32.93 (20.31-51.39) ng/mL vs 15.99(7.97-22.69) ng/mL, Z=-4.373, P<0.001]. Patients with HF-AF group had significantly higher test results [39.86 (27.20-59.21)] ng/mL than HF-SR group [24.74 (14.83-44.11)] ng/mL, Z=-6.783, P<0.001].In the HFmrEF and HFpEF subgroups, the plasma sST2 level of patients in the HF-AF group was higher than that in the HF-SR group (Z=-2.381, P=0.017; Z=-3.701, P<0.001).Spearman correlation analysis showed that, in HF-AF patients, plasma sST2 level was positively correlated with diastolic blood pressure, Hypertension, New York Association (NYHA) cardiac function classification Ⅲ to Ⅳ, white blood count(WBC), and the level of Alanine Aminotransferase (ALT), Υ-glutamine transaminase (Υ-GT), B-type natriuretic peptide (BNP) (r>0, P<0.05).Also, there is a negative correlation between sST2, left ventricular ejection fraction (LVEF) and estimated Glomerular Filtration Rate (eGFR) (r<0, P<0.05). At ROC analysis, sST2 showed predictive value in both HF-AF and HF-SR group, with an optimal cut-off value of 25.33 ng/mL(AUC 0.872, 95%CI: 0.805-0.935, P<0.001, sensitivity 81.1%, specificity 87.5%) and 23.34 ng/mL(AUC 0.665, 95%CI: 0.570-0.761, P<0.001, sensitivity 55.6%, specificity 77.5%).The AUC of BNP and sST2 in differential diagnosis of HF-SR and HF-AF was 0.604 and 0.699, respectively, and the AUC of sST2 was higher than that of BNP. Multi-factor COX analysis indicated that plasma sST2 level, BNP, NYHA cardiac function grading could be risk factors for cardiac events in HF patients. Plasma sST2, left atrial diameter (LA-D), and associated cardiomyopathy are risk factors for cardiac events in patients with HF-AF. The incidence of cardiac events in HF patients with sST2≥20.31 ng/mL was significantly higher than that of patients with sST2<20.31 ng/mL (χ2=7.625, P=0.006). The incidence of cardiac events in HF-AF patients with plasma sST2≥39.86 ng/mL was significantly higher than that in patients with sST2<39.86 ng/mL (χ2=4.287, P=0.038).@*Conclusions@#The plasma sST2 level in patients with HF-AF is significantly higher than that both in HF-SR and healthy controls. The diagnostic value of plasma sST2 in patients with HF-AF is higher than that in patients with HF-SR. It is suggested that sST2 are more valuable for the differential diagnosis of HF-SR, HF-AF than BNP. HF-AF Patients with plasma sST2 ≥ 39.86 ng/mL are prone to cardiovascular events.
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Objective To investigate the effects of FOXA2 on the proliferation of hepatocellular carcinoma cells and the tumorigenesis of nude mice, and to explore the effect of FOXA2 on the development of hepatocellular carcinoma. Methods Immunohistochemistiy and real-time quantitative PCR were used to detect the expression of FOXA2 in 35 pairs of hepatocellular carcinoma tissues and their matched paracancerous tissues. 293 T cells were used as controls to detect the expression level of FOX A 2 in hepatocellular carcinoma cell lines (HepG2, SMMC-7721 and SK-Hep1) by real-time quantitative PCR. The lentivirus was transfected into HepG2 cells, and there were 3 groups including no virus group (Mock group) , negative control virus group (NC group) and FOXA2-transfected over-expression virus group (FOXA2 group). Plate clone assays were used to detect the effect of FOXA2 on the proliferation of HepG2 cells in vitro and nude mice tumor and formation assays to detect the tumor weight and tumor weight inhibition rate after FOX A2-transfected overexpression of lentivirus-infected cells. Results The results of immunohistochemistry and real-time quantitative PCR showed that the expression of FOXA2 in cancer tissues was significantly lower than that in adjacent tissues (P < 0.01) , And the expression of FOXA2 in hepatoma cell lines (HepG2, SMMC-7721, SK-Hepl) was significantly lower than that of 293 T cells (P < 0.0001). After the lentivirus was transfected into HepG2 cells, the number of clones in the FOXA2 group was significantly less than that in the Mock group and the NC group (P < 0.05). The tumor formation of nude mice showed that the tumor weight of FOXA2 group was smaller than that of the corresponding blank control group and negative control group (P < 0.01).Conclusion FOXA2 is lowly expressed in hepatocellular carcinoma tissues and cells, which has the effect of inhibiting the proliferation of HepG2 cells in vitro and the growth of tumors in nude mice in vivo.
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Objective To study the early diagnostic value of high-sensitivity cardiac troponin Ⅰ(hs-cTnI) and soluble growth stimulating gene 2 protein (soluble suppression of tumorigenicity 2,sST2) in myocardial injury of acute organophosphorus pesticide poisoning (AOPP).Methods Totally 168 AOPP patients hospitalized from March 2014 to October 2018 were divided into the mild group (n=45),moderate group (n=55) and severe group (n=68).Another 30 healthy persons were served as the control group.The levels of cTnI,hs-cTnI,N-terminal B-type natriuretic peptide(NT-proBNP) and sST2 were detected at 4 h and 12 h after admission.SPSS 21.0 was used for statistical analysis.The measurement data were expressed by mean±standard deviation,two groups were compared by LSD-t test,and the multigroup comparison was made by single factor analysis of variance (ANOVA).The correlation analysis by Spearman correlation test (P＜0.05).Results At 1 h after admission,the hs-cTnI of AOPP patients with different degrees of poisoning was higher than that of control group,and that of severe group was higher than that of mild to moderate group.Comparison between groups was statistically significant (P＜0.05).However,there was no significant difference in the cTnI level (P＞0.05).At 4 h and 12 h after admission,the levels of cTnI and hs-cTnI increased with the increase of poisoning degree and the extension of time,and their level at 12 h after admission were significantly higher than those at 4 h after admission,with statistically significant difference between the two groups (P＜0.05).At 1 h after admission,the level of sST2 in the poisoned patients was higher than that in the control group,and the level in the severe group was higher than that in the mild to moderate groups.At 4 h and 12 h after admission,the level of sST2 was increased significantly,especially in the severe group.The level of sST2 at 12 h after admission was significantly higher than that at 4 h after admission (P＜0.05).The concentration of NT-proBNP was in normal range 1 h after admission,increased gradually at 12 h after admission,and the level of NT-proBNP in the severe group was significantly higher than that in the other groups (P＜0.05),and comparison between the groups was significantly different (P＜0.05).The correlation analysis showed that there was a positive correlation between hs-TnI and sST2 in AOPP patients (r=0.776,P＜0.01).hs-TnI and sST2 was positively correlated with the severity of AOPP (r=0.958,P＜0.01;r=0.844,P＜0.01).That is,the more severe the patient,the higher the concentration of hs-TnI and sST2,and the more serious myocardial injury.Conclusions Early detection ofhs-cTnI and sST2 levels in AOPP patients can identify early myocardial damage and objectively evaluate the extent of myocardial damage.
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@#[Abstract] Objective: To investigate the effects of FPR1 (formyl peptide receptor 1) antagonist Boc2 on migration, invasion, proliferation and tumorigenicity of human lung adenocarcinoma cells under hypoxia conditions. Methods: The protein expressions of hypoxia inducible factor 1α (HIF-1α) and FPR1 in human lung adenocarcinoma A549 cells induced by hypoxia was detected by Western blotting. FPR1 antagonist Boc2 was used to treat the hypoxia-induced A549 cells in vitro. The cells were divided into three groups: control group (cultured under normoxic condition), hypoxia group and hypoxia+Boc2 treatment group. Cell scratch test, transwell matrigel invasion assay and MTT method were used to detect the migration, invasion and proliferation of each group of cells, respectively. The A549 cells of each group were inoculated into nude mice to prepare xenograft model.After 4 weeks, the nude mice were sacrificed, and the differences in average tumor volume and mass, tumor formation rate, the expression of migration-related protein-E-cadherin (E-cad) and invasion-related protein-matrix metalloproteinase 9 (MMP-9) were analyzed. Results: Hypoxia induction can promote the expression of FPR1 protein in A549 cells in a time-dependent manner (P<0.05). The results of cell experiments showed that the ability of migration, invasion and proliferation of cells in hypoxia group were significantly higher than those in control group (P<0.01); while compared with hypoxia group, Boc2 treatment significantly inhibited the migration, invasion and proliferation of A549 cells (P<0.05). The results of nude mice experiments showed that the average volume and mass of nude mice in hypoxia group were significantly higher than those in the control group (all P<0.01). But the mean volume and mass of nude mice in hypoxia+Boc2 treatment group were significantly lower than those in the hypoxia group (all P<0.01). The rate of tumor formation in nude mice of hypoxia group was 100.0% (15/ 15), which was significantly higher than 60.0% (9/15) in the control group (χ2=7.500, P=0.006) and 73.3% (11/15) in the hypoxia + Boc2 treatment group (χ2=4.615, P=0.032). The expression of E-cad and MMP-9 protein in hypoxia group was significantly higher than that in control group (P<0.01), while Boc2 treatment significantly decreased the expression of E-cad and MMP-9 protein in hypoxia group (P<0.05). Conclusions: FPR1 antagonist Boc2 can significantly inhibit the migration, invasion, proliferation and tumorigenicity of hypoxia-induced human lung adenocarcinoma A549 cells, indicating that FPR1 plays an important role in the development and progression of human lung adenocarcinoma and may become a potential target of human lung adenocarcinoma treatment.
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Objective: To assess the diagnostic value of soluble suppression of tumorigenicity-2 (sST2) in heart failure (HF) by Meta-analysis. Methods: We searched the databases of CNKI, Wei Pu, CBMdisc,WanFang and Pubmed up to 2017-03-14 for diagnostic value of sST2 in HF patients. Corresponding references were enrolled and relevant data was extracted. Quality evaluation was conducted by quality assessment of diagnostic accuracy studies-2(QUADAS-2)method, effect of sST2 in HF diagnosis was analyzed by Stata14.0 and Revman software. Results: A total of 13 references were eligible including 5 English and 8 Chinese. Meta analysis showed that the diagnostic value of sST2 in HF had the pooled sensitivity at 79%, 95% CI (0.68-0.86);pooled specificity at 69%, 95% CI (0.58-0.79); positive like hood rate was 2.57, 95% CI(1.86-3.53), negative like hood rate was 0.31, 95%CI (0.21-0.46), diagnostic odds rate was 8.28, 95% CI (4.76-14.42); the area under ROC was 0.8. Deek's funnel plot demonstrated no publication bias in Meta-analysis. Conclusion: sST2 had moderate value in diagnosing HF; duo to the defect in methodology, large sample, scientific and reasonable random controlled trails should be conducted to confirm the diagnostic efficacy.
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Objective To study the relationships between differences in tumorigenicity and immu-nogenetic backgrounds of nude mice. Methods According to the Chinese Pharmacopoeia, positive and neg-ative groups were set up in both Laboratory A and B with ten nude mice in each group. Organ tissues were collected for clinicopathological analysis. Blood samples were collected and detected using flow cytometry. DNA was extracted and analyzed with 23 STR markers. Results The positive group of Laboratory B was in-valid (7/10 tumor formation). The two laboratories showed no significant difference in the results of patho-logical analysis, but had significant differences in CD25, CD8, CD4, Th1 and Th2. There were 13 and 18 polymorphic sites respectively found in nude mice of Laboratory A and B. Further analysis of the non-tumor-bearing nude mice in Laboratory B positive group revealed that CD25, Th2, D3Mit29 and D5Mit48 were the specific indexes. Conclusion Differences in tumorigenicity might be related to the diversity of immunoge-netic backgrounds of nude mice.
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BACKGROUND: The prognostic utility of cardiac biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and soluble suppression of tumorigenicity-2 (sST2), in non-cardiac surgery is not well-defined. We evaluated hs-cTnI and sST2 as predictors of 30-day major adverse cardiac events (MACE) in patients admitted to the surgical intensive care unit (SICU) following major non-cardiac surgery. METHODS: hs-cTnI and sST2 concentrations were measured in 175 SICU patients immediately following surgery and for three days postoperatively. The results were analyzed in relation to 30-day MACE and were compared with the revised Goldman cardiac risk index (RCRI) score. RESULTS: Overall, 30-day MACE was observed in 16 (9.1%) patients. hs-cTnI and sST2 concentrations differed significantly between the two groups with and without 30-day MACE (P < 0.05). The maximum concentration of sST2 was an independent predictor of 30-day MACE (odds ratio=1.016, P=0.008). The optimal cut-off values of hs-cTnI and sST2 for predicting 30-day MACE were 53.0 ng/L and 182.5 ng/mL, respectively. A combination of hs-cTnI and sST2 predicted 30-day MACE better than the RCRI score. Moreover, 30-day MACE was observed more frequently with increasing numbers of above-optimal cut-off hs-cTnI and sST2 values (P < 0.0001). Reclassification analyses indicated that the addition of biomarkers to RCRI scores improved the prediction of 30-day MACE. CONCLUSIONS: This study demonstrates the utility of hs-cTnI and sST2 in predicting 30-day MACE following non-cardiac surgery. Cardiac biomarkers would provide enhanced risk stratification in addition to clinical RCRI scores for patients undergoing major non-cardiac surgery.
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Humans , Biomarkers , Critical Care , Prognosis , Troponin I , TroponinABSTRACT
BACKGROUND: Stathmin as a critical protein involved in microtubule polymerization, is necessary for survival of cancer cells. However, extremely little is known about Stathmin in glioblastoma. So, this study was designed to elucidate the function of Stathmin gene in the tumorigenesis and progression of glioblastoma cells. METHOD: The lentiviral interference vector pLV3-si-Stathmin targeting Stathmin gene and the control vector pLV3-NC were established for the co-transfection of 293T cells together with the helper plasmids. Viral titer was determined via limiting dilution assay. Then pLV3-si-Stathmin and pLV3-NC were stably co-transfected into U373 and U87-MG glioblastoma cells. Expression levels of Stathmin protein in each group were determined by using Western Blot, and the proliferation and migration ability of the cells with downregulated Stathmin were evaluated through CCK8 assay and transwell invasion assay, respectively. Cell cycles and cell apoptosis were detected with flow cytometry. Finally, the effect of Stathmin in tumor formation was determined in nude mice. RESULT: DNA sequencing and viral titer assay indicated that the lentiviral interference vector was successfully established with a viral titer of 4 × 108 TU/ml. According to the results from Western Blotting, Stathmin protein expression level decreased significantly in the U373 and U87-MG cells after transfected with pLV3-si-Stathmin, respectively, compared with those transfected with pLV3-NC. In glioblastoma cells, the cell proliferation and migration were greatly inhibited after the downregulation of Stathmin protein. Flow cytometry showed that much more cells were arrested in G2/M phasein Stathmin downregulated group, compared with the non-transfection group and NC group. But Stathmin downregulation did not induce significant cell apoptosis. Tumor formation assay in nude mice showed that tumor formation was delayed after Stathmin downregulation, with a reduction in both tumor formation rate and tumor growth velocity. CONCLUSION: Stathmin downregulation affected the biological behaviors of U373 and U87-MG glioblastoma cells, inhibiting the proliferation and migration of tumor cells. Stathmin gene may serve as a potential target in gene therapy for glioblastoma.
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Animals , Mice , Down-Regulation/genetics , Glioblastoma/metabolism , Cell Proliferation/genetics , Stathmin/genetics , Transfection , Glioblastoma/genetics , Glioblastoma/pathology , Cell Line, Tumor , Stathmin/metabolism , Genetic VectorsABSTRACT
Objective To observe the tumorigenicity of High Five insect cell line in Balb/c nude mice,and make sure the safety of the cells when used in vaccine production.Methods Balb/c nude mice were randomly divided into 5 groups:the basic cell bank of High Five group,the highest limited passages of High Five group,HEp-2 cell group as positive control,CEF cell group as negative control,and blank control.Except of the blank control,cell suspension was injected subcutaneously into the nude mice in the different groups,respectively.At 3 and 12 weeks after injection,anatomical observation and histopathologic examination were performed to detect the tumor formation.Results At 3 and 12 weeks after injection,the tumorigenicity study results showed that no tumor developed at the transplantation site in the blank control group,negative group,and High Five groups.Histopathological examinations also showed no abnormality in these groups.Otherwise,squamous cell carcinoma was developed in the positive group at 3 weeks after injection.Conclusions High Five cells of basic cell bank and highest limited passages are not tumorigenic,and can be used in vaccine production safely.
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AIM:To elucidate the association between chronic kidney injury and interleukin-33 (IL-33;an alarmin)/suppression of tumorigencity 2 (ST2) in patients with systemic lupus erythematosus (SLE).METHODS:Serum levels of IL-33 and soluble ST2 (sST2) were assessed by ELISA in 50 SLE patients and 30 healthy controls (HC).RESULTS:The levels of IL-33 and sST2,and IL-33/sST2 ratio were significantly higher in SLE patients than those in the HC.The IL-33 and sST2 levels were positively associated with SLE disease activity index (SLEDAI),erythrocyte sedimentation rate (ESR),proteinuria and triglyceride,but negatively associated with complement C3.IL-33/sST2 ratio was positively associated with SLEDAI and estimated glomerular filtration rate (eGFR).Independent explanatory variables associated with high IL-33/sST2 included chronic kidney disease (CKD) staging and albumin (R2 =0.442),especially CKD staging.CONCLUSION:Elevated serum sST2 and IL-33 levels in SLE patients are correlated with disease activity and risk factors of kidney injury.IL-33/sST2 ratio may serve as a potential biomarker for chronic kidney injury in SLE patients.
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AIM:To elucidate the association between chronic kidney injury and interleukin-33 (IL-33;an alarmin)/suppression of tumorigencity 2 (ST2) in patients with systemic lupus erythematosus (SLE).METHODS:Serum levels of IL-33 and soluble ST2 (sST2) were assessed by ELISA in 50 SLE patients and 30 healthy controls (HC).RESULTS:The levels of IL-33 and sST2,and IL-33/sST2 ratio were significantly higher in SLE patients than those in the HC.The IL-33 and sST2 levels were positively associated with SLE disease activity index (SLEDAI),erythrocyte sedimentation rate (ESR),proteinuria and triglyceride,but negatively associated with complement C3.IL-33/sST2 ratio was positively associated with SLEDAI and estimated glomerular filtration rate (eGFR).Independent explanatory variables associated with high IL-33/sST2 included chronic kidney disease (CKD) staging and albumin (R2 =0.442),especially CKD staging.CONCLUSION:Elevated serum sST2 and IL-33 levels in SLE patients are correlated with disease activity and risk factors of kidney injury.IL-33/sST2 ratio may serve as a potential biomarker for chronic kidney injury in SLE patients.
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Objective Bladder cancer is one of the most common malignant tumors involving urinary system , yet its pathogene-sis has not been fully and thoroughly studied .The study aimed to de-tect the expression of LASS 2 in bladder cancer model of nude mice and investigate the relationship of LASS 2 with tumor proliferation and apoptosis as well as its possible molecular mechanism . Methods Tumor development in nude mice was observed through the establish-ment of orthotopic bladder cancer model by transplantation , bladder cancer metastasis model by subcutaneous injection and blank con-trol group.LASS2 expression and changes in proliferation and apoptosis were detected in tumor tissues of different parts . Results Bladder cancer cell injected subcutaneously metastasis model tumor formation rate of 100%.The two models were not found transfer phenomenon in vivo.Compared with blank control group (81.0%), LASS2 expression (60.0%, 14.0%) was significantly decreased in the inoculated group and subcutaneous implantation group ( P<0.05) .Compared with the blank control group ( 16.0%) , the expression of Ki67 in the inoculated group and subcutaneous implantation group increased (50.0%and 78.0%) (P<0.05).Compared with the in situ perfusion group, the expression of LASS2 (14.0%) was significantly decreased (P<0.05) and the expression of Ki67 (78.0%) was increased (P<0.05).Compared with the blank control group , the expression of Bcl-2 in subcutaneous implantation group and in si-tu perfusion group was significantly increased ( P<0.05) .Compared with the subcutaneous implantation group , the expression of Bcl-2 was increased in the in situ perfusion group ( P<0.05) , while the expression of Bcl-x1 in the in situ implanted tumor was higher than that in the other two groups (P<0.05).The expression level of Bax and caspase3 in each group was not statistically significant (P>0.05) .Compared with the blank control group , the expression of Bim was significantly decreased in the subcutaneous implantation group (P<0.05). Conclusion The expression of LASS2 may be related to the tumorigenicity , proliferation and apoptosis in EJ blad-der cancer cells .
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OBJECTIVE Cervical cancer is the third most malignant tumor in the world. Farnesoid X receptor (FXR) is a member of nuclear receptor superfamily. It is highly expressed in liver, kidney and small intestine, while it showed low expression level in other tissues. It not only plays an important role in the metabolism of bile acids and sugars, but also in the production of chronic inflammation in the early stage of cancer, the proliferation and migration of tumor. Compared with the normal tissue, the expression of FXR in most tumor tissues decreased. But there is no correlation between cervical cancer and FXR. So we aimed to find out the relationship between FXR and cervical cancer. METHODS A clinical study using qPCR, western blot and immunohistochemistry detected the expression of FXR in tumor tissues and normal tissues of clinical patients. FXR was activated by agonists or over-expressed by lentivirus. MTT, clone formation and flow cytometry were used to detect the relationship between FXR and proliferation of cervical cell lines. Tumor growth ability of FXR was detected by nude mice tumorigenicity. The interaction between FXR and CDKN2A-p14ARF-MDM2-p53 pathway was detected by qPCR, Western blot and immunohistochemistry. RESULTS FXR was decreased in cancer tissues compared to normal control. Activation of FXR by agonist or constitutively- over- expression of FXR inhibited cervical cell proliferation. Over- expressed FXR attenuated Caski, Hela and Siha xenograft tumor growth in nude mice compared with control. Over-expression of FXR caused G1 cell-cycle arresting and up-regulated CDKN2A-p14ARF-MDM2-p53 pathway. CONCLUSION FXR inhibits cervical cancer cell proliferation and cervical tumorigenicity which is related to CDKN2A-p14ARF-MDM2-p53 pathway. Activation or overexpression of FXR may be a potential target for the treatment of cervical cancer.