BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α)...BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.展开更多
Acute myocardial infarction （AMI） is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-a （TNF-a） on ventricular arrhythmias induced byAMI in rats in vivo. ...Acute myocardial infarction （AMI） is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-a （TNF-a） on ventricular arrhythmias induced byAMI in rats in vivo. Two hundred and forty male Wistar rats were randomized into a sham- operation group, an AMI group, and a recombinant human tumor necrosis factor receptor：Fc fusion protein（rhTNFR：Fc） group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery （LAD）, and there was no ligation but operation in the sham-operation group. The rhTNFR：Fc group was treated with rhTNFR：Fc（10 mg/kg）, a TNF-a antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-a among different groups were detected by histochemistry and real-time fluorescent quantitative PCR. Expression of TNF-a increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR：Fc group. The time- windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR：Fc group showed a lesser expression of TNF-a protein and a lower incidence of ventricular arrhythmias （P〈0.05）. There was no obvious change in the sham-operation group. The expression of TNF-a induced by AMI could contribute to the onset of ventricular arrhythmias.展开更多
AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-...AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.展开更多
Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clini...Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.展开更多
BACKGROUND： The tumor necrosis factor recepter associated factor （TRAF） 6 is an important intracellular adapter protein that plays a pivotal role in activating multiple inflammatory and immune related processes ind...BACKGROUND： The tumor necrosis factor recepter associated factor （TRAF） 6 is an important intracellular adapter protein that plays a pivotal role in activating multiple inflammatory and immune related processes induced by cytokines. TRAF6 represents a strong candidate susceptibility factor for sepsis. We investigated whether polymorphisms at the TRAF6 gene are associated with the susceptibility to and severity of sepsis.METHODS： A hospital-based case-control study was conducted with 255 patients with sepsis and 260 controls who were recruited from Zhengzhou, China. Haplotype tagging single nucleotide polymorphisms （htSNPs） were selected from the HapMap database and genotyped using the SNPstream genotyping platform. The associations with the susceptibility and disease severity of sepsis were estimated by logistic regression, and adjusted for age, sex, smoking, drinking, chronic diseases status, APACHEII score and critical illness status.RESULTS： A total of 13 TRAF6 SNPs were tagged by 7 htSNPs. Five htSNPs （rs5030490, rs5030411, rs5030416, rs5030445 and rs3740961） were genotyped in the case control study. Genotype frequencies of the htSNPs were conformed to the Hardy-Weinberg equilibrium in both patients and controls. No significant association was found between the 5 htSNPs and the susceptibility to and severity of sepsis. Compared with the main haplotype -11120A/-10688T/-9423A/805G/12967G, no certain haplotype was associated with the signi？ cantly susceptibility to or severity of sepsis.CONCLUSION： TRAF6 gene polymorphisms might not play a major role in mediating the susceptibility to and severity of sepsis in the Chinese population. A larger population-based case-control study is warranted.展开更多
文摘BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.
文摘Acute myocardial infarction （AMI） is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-a （TNF-a） on ventricular arrhythmias induced byAMI in rats in vivo. Two hundred and forty male Wistar rats were randomized into a sham- operation group, an AMI group, and a recombinant human tumor necrosis factor receptor：Fc fusion protein（rhTNFR：Fc） group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery （LAD）, and there was no ligation but operation in the sham-operation group. The rhTNFR：Fc group was treated with rhTNFR：Fc（10 mg/kg）, a TNF-a antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-a among different groups were detected by histochemistry and real-time fluorescent quantitative PCR. Expression of TNF-a increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR：Fc group. The time- windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR：Fc group showed a lesser expression of TNF-a protein and a lower incidence of ventricular arrhythmias （P〈0.05）. There was no obvious change in the sham-operation group. The expression of TNF-a induced by AMI could contribute to the onset of ventricular arrhythmias.
基金Supported by Grant-in-Aid for Research from the Third-Term Comprehensive Control Research for Cancer Center of the Ministry of Health, Labor and Welfare, JapanGrant from the Ministry of Education, Culture, Sports, Science and Technology, Japan(KIBAN-B)the "Collaborative Development of Innovative Seeds" Grant Program from the Japan Science and Technology Agency
文摘AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.
文摘Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.
文摘BACKGROUND： The tumor necrosis factor recepter associated factor （TRAF） 6 is an important intracellular adapter protein that plays a pivotal role in activating multiple inflammatory and immune related processes induced by cytokines. TRAF6 represents a strong candidate susceptibility factor for sepsis. We investigated whether polymorphisms at the TRAF6 gene are associated with the susceptibility to and severity of sepsis.METHODS： A hospital-based case-control study was conducted with 255 patients with sepsis and 260 controls who were recruited from Zhengzhou, China. Haplotype tagging single nucleotide polymorphisms （htSNPs） were selected from the HapMap database and genotyped using the SNPstream genotyping platform. The associations with the susceptibility and disease severity of sepsis were estimated by logistic regression, and adjusted for age, sex, smoking, drinking, chronic diseases status, APACHEII score and critical illness status.RESULTS： A total of 13 TRAF6 SNPs were tagged by 7 htSNPs. Five htSNPs （rs5030490, rs5030411, rs5030416, rs5030445 and rs3740961） were genotyped in the case control study. Genotype frequencies of the htSNPs were conformed to the Hardy-Weinberg equilibrium in both patients and controls. No significant association was found between the 5 htSNPs and the susceptibility to and severity of sepsis. Compared with the main haplotype -11120A/-10688T/-9423A/805G/12967G, no certain haplotype was associated with the signi？ cantly susceptibility to or severity of sepsis.CONCLUSION： TRAF6 gene polymorphisms might not play a major role in mediating the susceptibility to and severity of sepsis in the Chinese population. A larger population-based case-control study is warranted.
