Research progress of soluble growth stimulating gene 2 protein in cardiovascular disease / 中国基层医药

Growth stimulating gene 2 (ST2) protein is a member of the interleukin-1 receptor family. It is mainly divided into a soluble secreted form sST2 and a transmembrane form ST2L. sST2 is a decoy receptor that competitively binds to interleukin-33 to block the interleukin-33/ST2L signaling pathway, worsening myocardial hypertrophy, fibrosis, and ventricular dysfunction. Measuring sST2 is of important value for diagnosis and/or prognosis evaluation of cardiovascular diseases. This paper mainly reviews the research progress in the relationship between cardiovascular diseases such as heart failure, coronary heart disease, hypertension, atrial fibrillation, myocarditis, cardiomyopathy, acute aortic dissection, and pulmonary hypertension, and sST2.

IL17A and IL17RA gene polymorphisms in Fanconi anemia

Abstract Fanconi anemia is a rare autosomal recessive disease. In this disease, cytokine pathways can induce the bone marrow failure that is observed in individuals with Fanconi anemia. Interleukin IL-17 exhibits a protective effect in organisms because it induces neutrophil recruitment and shows a pathological role in several models of autoimmune diseases, periodontal disease, cancer, allograft rejection, and graft versus host disease. Polymorphisms in the IL17A and IL17RA genes were evaluated from DNA in saliva, comparing individuals with or without Fanconi anemia, using models of genotypic transmission (additive, dominant, and recessive). Polymorphisms in the IL17A and IL17RA genes (rs2241044 [C allele], rs879577 [C allele], rs9606615 [T allele], and rs2241043 [C allele]) were risk factors for developing Fanconi anemia. We also performed an analysis of gene markers with clinical variables in the Fanconi group. Polymorphisms in the IL17A gene (rs3819025 [A allele] and rs2275913 [G allele], respectively) were associated with an age of less than 20 years (p = 0.026; RP 0.65) and the female sex (p = 0.043; RP 0.88). The IL17RA gene was also associated with age and the presence of leukoplakia (a potentially malignant oral disorder). An age of less than 20 years was associated with rs917864 (T allele; p = 0.036; RP 0.67). The presence of leukoplakia was associated with rs17606615 (T allele; p = 0.042; RP 0.47). To our knowledge, this is the first study that associates IL17A and IL17RA gene polymorphisms with Fanconi anemia and examines rs2241044 polymorphisms in scientific literature thus far.

Association of interleukin-2 receptor expression with liver pathological changes in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the association between serum interleukin (IL) and liver pathological changes in patients with chronic hepatitis B (CHB). MethodsA total of 59 patients with CHB who were treated in Putuo District Central Hospital of Shanghai from February 2018 to February 2019 were enrolled as subjects, and liver biopsy was performed for all patients. According to the degree of liver inflammation, the patients were divided into mild inflammation (G1-G2) group and severe inflammation (G3-G4) group, and according to the degree of liver fibrosis, the patients were divided into mild fibrosis (S0-S2) group and severe fibrosis (S3-S4) group. Serum liver function parameters, blood lipids, interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured for all patients. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon non-parametric test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was also performed. ResultsThe degree of liver fibrosis increased with the increase in liver inflammation (rs=0.538, P＜0.001). Compared with the mild inflammation group, the severe inflammation group had significantly higher serum levels of alanine aminotransferase ［95.00 (45.00-16925) U/L vs 51.00 (29.00-88.00) U/L, Z=-2.625, P=0.009］, aspartate aminotransferase ［54.50 (34.75-84.50) U/L vs 38.00 (30.00-49.00) U/L, Z=-2.014, P=0.044］, and gamma-glutamyl transpeptidase ［91.00 (56.72-192.25) U/L vs 44.00 (24.00-100.00) U/L, Z=-2.400, P=0.016］. The severe fibrosis group had a significantly higher serum level of high-density lipoprotein than the mild fibrosis group ［0.97 (0.32-1.08) mmol/L vs 1.23 (0.36-1.38) mmol/L, Z=-1.300, P=0.008］. The severe inflammation group had a significantly higher serum level of IL-2 receptor than the mild inflammation group ［704.00(418.00-103800) U/ml vs 436.00(335.00-555.00) U/ml, Z=-3.405, P=0.001］, and the severe fibrosis group had a significantly higher serum level of IL-2 receptor than the mild fibrosis group ［735.00(523.00-890.50) U/ml vs 447.00 (351.50-624.50) U/ml, Z=-5.358, P=0.001］. ConclusionThe degree of liver inflammation is positively correlated with that of liver fibrosis, while the serum level of IL-2 receptor increases with the increase in the degrees of liver inflammation and fibrosis, indicating that IL-2 receptor can reflect the degrees of liver inflammation and fibrosis to some extent.

An association between single nucleotide polymorphisms of IL-23R gene and Keshan disease in Northwest Chinese Han population / 中华地方病学杂志

Objective To investigate the relationship between single nucleotide polymorphisms of interleukin 23 receptor (IL-23R) gene and Keshan disease (KD) in Northwest Chinese Han population.Methods A total of 285 Chinese Han subjects from Huangling,Shaanxi,including 79 KD patients (case group) and 206 control subjects (control group) were involved in this study.Genomic DNA was extracted from peripheral venous blood.The polymorphism of genetic variation was genotyped by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF).All sample groups were tested for Hardy-Weinberg equilibrium using goodness-of-fit x2 test.Differences in genotype distribution between two groups were compared by x2 test.Logistic regression analysis was applied to detect association using age as a confounding factor.Results The gene frequency distribution of IL-23R gene rs10889677 in case group and control group conformed to the Hardy-Weinberg equilibrium (x2 =0.254,P ＞ 0.05).Correlation analysis results:the difference of genotype frequency of IL-23R gene rs10889677 in case group (CC,CA,AA were 6.3％,36.7％,57.0％,respectively) and control group (CC,CA,AA were 5.3％,43.2％,51.5％,respectively) was not statistically significant (x2 =1.008,P ＞ 0.05).After age adjustment,there was no significant difference in genotype frequency of IL-23R gene rs10889677 (x2sdj =0.669,P ＞ 0.05) between two groups.Conclusion There is no correlation between IL-23R gene rs10889677 and KD in Northwest Chinese Han population.

Efficacy and Safety of Benralizumab for Korean Patients With Severe, Uncontrolled Eosinophilic Asthma

PURPOSE: In the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO. METHODS: SIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12–75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/µL. This subgroup analysis evaluated Korean patients from this group. RESULTS: Of 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/µL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13–0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06–0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039–0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143–0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (−0.27 [95% CI, −0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, −0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.

Expression and Clinical Significance of IL-17BR in Inflammatory Bowel Disease / 胃肠病学

Background:There is no specific therapy for inflammatory bowel disease(IBD),and the pathogenesis of IBD is not fully clear. Aims:To explore the expression and clinical significance of IL-17BR in colon mucosa and peripheral blood mononuclear cell(PBMC)of patients with IBD. Methods:Colon mucosal biopsy specimens of 40 Crohn's disease(CD) patients,32 ulcerative colitis(UC)patients and 25 healthy controls and PBMC of 30 CD patients,27 UC patients and 25 healthy controls were collected. The expressions of IL-17BR in colon mucosa and PBMC were determined by immunohistochemistry and flow cytometry,respectively,and correlations between IL-17BR expression and levels of CRP, ESR,CDAI score and Mayo score were analyzed. Serum levels of TNF-α before and after infliximab(IFX)treatment were determined by ELISA,and correlations with IL-17BR were analyzed. Results:Compared with healthy controls,IL-17BR expressions in colon mucosa of CD and UC patients were significantly increased(P<0.05). IL-17BR expressions were significantly higher in active CD and UC patients than in remission CD and UC patients(P <0.05). No significant differences in IL-17BR expression in PBMC were found among CD,UC patients and healthy controls(P>0.05). The expression of IL-17BR in colon mucosa was positively correlated with CRP,ESR,CDAI score or Mayo score in CD,UC patients(P <0.05). After treatment with IFX,expression of IL-17BR in colon mucosa and serum TNF-α level were significantly decreased in CD patients(P<0.01). Expression of IL-17BR was positively correlated with serum TNF-α level in CD patients(P<0.05). Conclusions:The increasing of IL-17BR expression in IBD patients is closely correlated with activity of inflammation and TNF-α level. IL-17BR may play a vital role in immune response of intestinal mucosa,and can be used as a new marker for reflecting the activity of IBD.

New progress in the study of IL-17 in renal diseases / 中国医师杂志

Interleukin (IL)17 is a pro-inflammatory cytokine produced by the activated CD4 + T cell subsets (Th17).It can regulate the function of cells involving in the pathogenesis of inflammation,autoimmune,neoplastic disease.The IL-17 family consists of six family members,IL-17A,IL-17B,IL-17C,IL-17D,IL-17E and IL-17F,respectively.The IL-17 receptor family consists of five members,IL-17RA,IL-17RB,IL-17RC,IL-17RD and IL-17RE,respectively.This review summarizes the characteristics and functions of the IL-17 family,the IL-17 receptor family,and the Th17/IL-17 axis.It also reviews the research about IL-17 in various kidney diseases.

Synthesis and biological evaluation of 18F-AlF-NOTA-c (CGRRAGGSC) / 中华核医学与分子影像杂志

Objective To synthesize 18F-AlF-1,4,7-triazacyclononane-l,4,7-triacetic acid (NOTA)-c (CGRRAGGSC),which could specifically bind to the α chain of interleukin (IL)-11 receptor (IL-11 R),and evaluate its targeting potential to IL-11 R-positive tumors.Methods Polypeptide c (CGRRAGGSC) was first coupled with NOTA and then labeled with 18F by AlF labeling method.The radiochemical purity and radiochemical yield of 18F-AlF-NOTA-c(CGRRAGGSC) were analyzed by high performance liquid chromatography,and the stability in vitro was evaluated.The tracer biodistribution in tumor-bearing mice (cell line SKOV3) was evaluated by the dynamic imaging with microPET 30 min,1 h,2 h after injection of 18F-AlF-NOTA-c (CGRRAGGSC).The tracer kinetics was performed in normal mice.Pharmacokinetics parameters were calculated using DAS2.0 software.Results The radiochemical purity of 18F-AlF-NOTA-c(CGRRAGGSC) was higher than 95％ and the radiochemical yield was (30.0±7.4)％.It could be stably maintained in phosphatebuffered solution and plasma for at least 2 h.MicroPET imaging showed that 18F-AlF-NOTA-c(CGRRAGGSC)had a good affinity to SKOV3 tumor.The tumor/muscle ratios at 30 min,1 h,2 h after the injection of 18F-AlF-NOTA-c(CGRRAGGSC) were 6.26±2.98,7.19±3.63 and 9.05±4.30,respectively.The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys.The T1/2α and T1/2β were (0.38±0.14) h and (2.64±0.28) h,respectively.Conclusions 18F-AlF-NOTA-c(CGRRAGGSC) is easy to be synthesized and has a good affinity to IL-11R-positive tumors.It will be a potential IL-11R-targeting imaging agent.

Role of interleukin-4 receptor in renal fibrosis following renal ischemia-reperfusion injury in mice / 中华麻醉学杂志

Objective To evaluate the role of interleukin-4 receptor (IL-4R) in renal fibrosis following renal ischemia-reperfusion (I/R) injury in mice.Methods Twelve male wild type BALB/C mice and 12 IL-4Rα gene-knockout mice,aged 8-10 weeks,weighing 20-30 g,were used in the study.The mice of either type were divided into 2 groups (n =6 each) using a random number table:sham operation group (group S) and group I/R.In group I/R,renal I/R was induced by occlusion of the right renal artery for 1 h with atraumatic microclips followed by 2 weeks of reperfusion.The right renal artery was only isolated in group S.At 2 weeks of reperfusion,blood samples were taken from the orbital vein for determination of the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr).The renal tissues were obtained,and the renal fibrosis area was measured by Sirius Red staining.The expression of fibronectin (FN),collagen Ⅰ (COL-Ⅰ) and α-smooth muscle actin (α-SMA) in renal tissues was detected by immunofluorescence.The expression of signal transducer and activator of transcription 6 (STAT6) and phospho-STAT6 in renal tissues was determined by Western blot.The ratio of phoshop-STAT6 to STAT6 was calculated to reflect the phosphorylation of STAT6.Results Compared with group S of wild type mice,the serum BUN and Cr concentrations and renal fibrosis area were significantly increased,the expression of FN,COL-Ⅰ and α-SMA in renal tissues was significantly up-regulated,and the phosphorylation of STAT6 in renal tissues was significantly increased in group I/R of wild type and IL-4Rα KO mice (P＜0.05).Compared with group I/R of wild type mice,the serum BUN and Cr concentrations and renal fibrosis area were significantly decreased,the expression of FN,COL-Ⅰ and α-SMA in renal tissues was significantly down-regulated,and the phosphorylation of STAT6 in renal tissues was significantly decreased in group I/R of IL-4RαKO mice (P＜0.05).Conclusion The mechanism of renal fibrosis following renal I/R injury is partially related to IL-4R,and IL-4R results in renal fibrosis through promoting activation of STAT6 signaling pathway in mice.

IL-25 and allergic airway inflammation / 解放军医学杂志

Allergic airway inflammation is manifested as infiltration of CD4+ T cells and eosinophils in the airway,increased secretion of mucus,airway hyper-reactivity and airway remodeling.IL-25 is a member of the IL-17 family,which can promote and exacerbate Th2 cytokine-mediated airway inflammation after binding to its receptor IL-17RB.The increased IL-25 can induce the secretion of Th2 cytokines,including IL-4,IL-5 and IL-13,which may result in the local infiltration of eosinophils,airway hyperreactivity and therefore the injury of airway.As IL-25 plays an important role in allergic airway inflammation,the present paper would focus on the relationship between IL-25 and allergic airway inflammation.

Effect of remifentanil on metastasis of human lung adenocarcinoma cells and expression of interleukin-7 receptors / 中华麻醉学杂志

Objective To evaluate the effects of remifentanil on the metastasis of human lung adenocarcinoma cells and expression of interleukin-7 receptor (IL-7R).Methods Human adenocarcinoma cell line A549 cells were seeded in 24-well plates at a density of 2× 105 cells/ml (72 wells).The cells were divided into 4 groups (n =18 each) using a random number table:normal control group (group C) and remifentanil 2,4 and 6 ng/ml groups (group R2,group R4,group R6).In R2,R4 and R6 groups,remifentanil at the final concentrations of 2,4 and 6 ng/ml was added,respectively,and the cells were incubated for 4 h.The equal volume of normal saline was given instead of remifentanil in group C.The cells were collected at 24 h after the following incubation.The invasion of cells was determined by Transwell invasion assay,and the invaded cells were counted.The migration of cells was determined by cell scratch test,and cell migration rates were calculated.The expression of IL-7R in cells was detected by Western blot.Results Compared with group C,the number of invaded cells and cell migration rates were significantly decreased in R2,R4 and R6 groups,and the expression of IL-7R was down-regulated in R4 and R6 groups (P＜0.05).Compared with group R2,the number of invaded cells and cell migration rates were significantly decreased,and the expression of IL-7R was down-regulated in R4 and R6 groups (P＜0.05).Compared with group R4,the number of invaded cells and cell migration rates were significantly decreased,and the expression of IL-7R was down-regulated in group R6 (P＜0.05).Conclusion Remifentanil can inhibit metastasis of human lung adenocarcinoma cells and down-regulate the expression of IL-7R.

Serial serum soluble stromelysirn-2 testing to assess prognosis in elderly patients with acute heart failure / 中华老年医学杂志

Objective To investigate the predicting value of serial serum human stromelysin-2 (ST2)testing on prognosis in elderly patients with acute heart failure(AHF).Methods 75 AHF patients aged 60 to 90 were selected in our study who were in Beijing Hospital during 2013.1 ～ 2014.8,blood sampling of serum ST2 took place at admission and 72-96 h later.Moreover,38 healthy people aged 70 to 80 were chosen as control group.Follow-up was performed 1 year after acute attack.We defined the end of observation as recurrence of heart failure or any cause of death.The data was analyzed by SPSS19.0.Results Among 55 AHF patients,sST2 level was higher in patients with endpoint events than those without it on the two moment(P=0.000).And we found that the change in sST2 was higher in patients with endpoint events than those without it(P=0.023);and the percentage change in sST2 was also significantly different(P=0.033).Receiver operator curve analysis of the change in sST2 from baseline to 72-96 h later was strongly reflective of prognosis with area under the curve(AUC) of 0.696(P=0.013).And the change in sST2 Combined with the sST2 level at admission to predict the prognosis of AHF,the result would be more exciting,the area under the receiver operating characteristic (ROC) curve is 0.861 (P ＜ 0.001).The endpoint event rate of the patients whose level of sST2 at admission was below 1408 ng/L and the change level in sST2 below 101 ng/L was 21.4％(3/14),while the data in patients whose level of sST2 at admission is above 1 408 ng/L and the change level in sST2 above 100 ng/L was 85.7％(12/14).Conclusions in elderly patients of AHF,sST2 elevate markedly.The result shows that the level of sST2 may be used to evaluate AHF prognosis.And the change in sST2 are able to predict the prognosis of AHF.Compared with NT-proBNP,serial sST2 testing appears to be a promising candidate for monitoring these patients.

Soluble ST2 Testing: A Promising Biomarker in the Management of Heart Failure / Teste com ST2 Solúvel: Um Biomarcador Promissor no Tratamento da Insuficiência Cardíaca

Abstract ST2 is a member of the interleukin-1 receptor family biomarker and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress and fibrosis. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in both chronic and acute heart failure. It is a new biomarker that meets all required criteria for a useful biomarker. Of note, it adds information to natriuretic peptides (NPs) and some studies have shown it is even superior in terms of risk stratification. Since the introduction of NPs, this has been the most promising biomarker in the field of heart failure and might be particularly useful as therapy guide.

Resumo ST2 é um biomarcador pertencente à família dos receptores de interleucina-1 e concentrações do ST2 solúvel refletem fibrose e estresse cardiovascular. Estudos recentes demonstram que o ST2 solúvel é um forte preditor de desfechos cardiovasculares em pacientes com insuficiência cardíaca crônica e aguda. Trata-se de um novo biomarcador que preenche critérios necessários para uso na prática clínica. Ele acrescenta informação aos peptídeos natriuréticos (PNs) e em alguns estudos tem sido até superior a estes em relação à estratificação de risco. Desde a introdução dos PNs, este é o biomarcador mais promissor na área de insuficiência cardíaca e pode vir a ser particularmente útil para guiar a terapia.

The expressions of IL-33 and ST2 receptor in nervous system and their roles in pain / 中国医师杂志

Interleukin-33 (IL-33),a novel member of IL-1 family,is a multifunctional cytokine.IL-33 can act as a transcriptional repressor.It can also bind to growth stimulation expressed gene 2 protein (ST2) to induce the activation of some inflammatory cells.IL-33 is extensively expressed in nervous system.Some studies showed that the levels of IL-33 and ST2 were significantly changed in pain.Some reports demonstrated that the IL-33/ST2 signaling pathway played critical roles in them.This present article will review the biological characteristics of IL-33/ST2 and their expressions in nervous system and significance of interventional pain related diseases.

Expression of IL-9 and its receptor mRNA in nasal mucosa of allergic rhinitis mice / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the expression and roles of IL-9 and its receptor (IL-9R) mRNA in the nasal mucosa of ovalbumin-induced allergic rhinitis (AR) mice. METHODS Sixteen Balb/c mice were selected and randomly divided into two groups with 8 mice in each group. Mice were used for establishing the animal model of AR with ovalbumin sensitization as AR group, at the same time, the physiological saline as the control group. In each group, 4 mice were randomly taken from each group, and the pathological examination showed that the model was successful. The nasal mucosa was taken from the remaining 4 mice in each group and then to detect IL-9 and IL-9R mRNA in nasal mucosa of the two groups by using real-time quantitative PCR. RESULTS The expression of IL-9 and IL-9R mRNA could be detected in both the control and AR groups. The expression levels of IL-9 and IL-9R mRNA in the nasal mucosa of the AR group were both higher than that in the control group (P<0.05). The expression level of IL-9 mRNA was positively correlated with the expression of IL-9R mRNA in the nasal mucosa of mice (r =0.857, P<0.05). CONCLUSION IL-9 and its receptor IL-9R are involved in the development of AR, and play an important role in the development of allergic rhinitis. It provides a new perspective for the further understanding of the pathogenesis of AR and provides a new clue for the treatment of allergic rhinitis.

Pustular psoriasis:an update on genetics / 中华皮肤科杂志

Pustular psoriasis is not a rare inflammatory skin disease, and is characterized by sudden onset of generalized erythema and sterile pustules complicated by chills, high fever, neutrophilia and elevated levels of C?reactive protein. Due to frequent recurrence, it greatly impacts the quality of life in patients. Recently, it has been gradually found that IL36RN, CARD14 and AP1S3 mutations are associated with the occurrence of pustular psoriasis, and accordingly some new therapeutic approaches have emerged. This review summarizes recent advances in genetics of pustular psoriasis.

Correlation of the levels of interleukin-17 and its receptor with myasthenia gravis / 中华神经科杂志

Objective To investigate the correlation of plasma interleukin ( IL)-17 level and IL-17 receptor (IL-17R) expression in the thymus of patients with myasthenia gravis (MG).Methods The blood samples of 63 patients (38 with glucocorticoid treatment, 25 with thymus removal) who admitted to Henan Provincial People′s Hospital between 2010 and 2014 were collected at three different stages: pre-treatment, 1 week post-treatment and 1 month post-treatment.The blood samples of 42 healthy controls were also collected.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-17 in plasma.Twenty-five thymus tissues from MG patients and another 12 thymus tissues from patients with congenital heart disease who had surgery therapy were also collected.Reverse transcription polymerase chain reaction was used to evaluate the mRNA levels of IL-17R.The possible correlation between the expression of IL-17 and IL-17R with MG was analyzed.Results Before treatment, the levels of IL-17 in the plasma were much higher in all the MG patients ( both ocular and generalized) when compared to the healthy controls ( controls (3.2 ±0.7) pg/ml, MG patients (8.5 ±1.7) pg/ml, t =2.450, P 0.05, compared to the healthy controls).In the surgery therapy cases, the IL-17 levels were also reduced after the thymus removal ( pre-surgery (8.8 ±1.4) pg/ml, 1 week after surgery (5.3 ±0.7) pg/ml, t=1.950, P<0.05;1 month after surgery (3.0 ±0.4) pg/ml, t=2.683, P<0.01).In the thymus tissues of the MG patients, the mRNA levels of IL-17R were much higher than that of the controls ( relative level 2.31 folds, t =2.682, P <0.01).Meanwhile, a positive correlation was found between the plasma IL-17 levels and the relative IL-17R levels in thymus tissues ( r =0.945 4, P <0.01 ).Furthermore, IL-17 was positively correlated with quantitative myasthenia gravis scores (QMGS) either pre-treatment (r =0.798 1, P <0.01) or post-treatment (r=0.906 5, P<0.01).And IL-17R was positively correlated with QMGS pre-treatment (r=0.775 5, P<0.01).Conclusions IL-17 is increased in the plasma of MG patients (both ocular and generalized) , and is decreased upon the glucocorticoid treatment or surgery therapy, suggesting that it can be used as a parameter to determine the therapeutic effects.IL-17R is increased in the thymus tissues of MG patients, suggesting that it can potentially be used as a pathological diagnosis parameter.

Role of immune inflammation in the formation of intracranial aneurysm / 国际脑血管病杂志

ObjectiveToinvestigatetheroleofimmuneinflammatoryreactionintheformationof intracranial aneurysm. Methods The intracranial aneurysms in 40 patients of craniotomy ( intracranial aneurysm group) and the vascular specimens in 20 craniotomy patients w ith traumatic brain injury (control group) w ere col ected. Fluorescence quantitative polymerase chain reaction w as used to detect the expression of interleukin (IL)-17 receptor in the arterial w al . Flow cytometry w as used to detect the Th-17 cel s in peripheral blood. Enzyme-linked immunosorbent assay w as used to measure the levels of IL-17, IL-6 in the arterial w al and tumor necrosis factor-α( TNF-α) in peripheral blood. Results There w ere no significant differences in the age (62.6 ±8.7 years vs.61.4 ±7.9 years;t=0.342;P=0.681), proportions of male (60.0%vs.65.0%; χ2 =0.246, P=0.434), hypertension ( 12.5%vs.10.0%; χ2 =0.315, P=0.492), diabetes (75.0%vs.10.0%; χ2 =0.284, P=0.482), and smoking (35.5%vs.30.0%; χ2 =0.224, P=0.413) betw een the intracranial aneurysms group and the control group. The expression of IL -17 receptor in the arterial w al (0.106 ±0.032 vs.0.264 ±0.071; t=5.115, P=0.001) and the proportion of Th17 cels in peripheral blood (2.75%±0.53%vs.7.18%±1.54%; t=8.436, P<0.001) and IL-17 level ( 7.32 ±1.82 μg/L vs.22.64 ±4.51 μg/L; t= 8.357, P< 0.001 ) in the control group w ere significantly low er than those in the intracranial aneurysm group. The levels of IL-6 (1.15 ±0.24 μg/L vs. 19.64 ±4.16 μg/L; t=9.527, P<0.001) and TNF-α(1.43 ±0.31 μg/L vs.26.17 ±4.32 μg/L; t=9.816, P<0.001) in the arterial wal in the control group were significantly lower than those in the intracranial aneurysm group. Conclusions The expression of IL-17 receptor in the arterial w al , the proportion of the Th17 cels and IL-17 level in peripheral blood were increased in patients with intracranial aneurysms. Immune inflammation may be involved in the formation of intracranial aneurysm.

Establishment of a novel high throughput screening assay for identifying small molecular antagonists of human interleukin-6 receptor / 军事医学

Objective To establish a high throughput screening assay for identifying human small molecular antagonists targeted IL-6R.Methods The full length gene of the human IL-6R extracellular region was amplified by PCR and cloned into a eukaryotic expression vector to construct recombination expression plasmid pABHis -IL6R that was then transfected transiently into HEK293T cells to prepare recombination protein IL-6R.Western blotting assay and receptor-ligand binding experiment were used to analyze the bioactivity of IL-6R.A new screening method based on ELISA was established using the function of IL-6R binding to its ligand and the characteristics of Fc fragment binding to IgG-HRP.Then Z′-factor was calculated and a known antagonist ab 47215 was used to assess the stability and reliability of the new assay .Results Recombination plasmid pABHis-IL6R was constructed and soluble IL-6R was prepared.IL-6R reported herein could be recognized by an anti-IL-6R antibody and specifically bind to its ligand in a dose response manner .A Z′-factor of 0.53 was obtained that could serve high throughput screening assay .Ab47215 , as a known specific antagonist , was able to block rhIL-6 from binding to the receptor in a dose-dependent manner in the new screening assay , the IC50 of which was (0.55 ± 0.11)μg/ml.Conclusion An innovative and easy screening assay for identifying human IL-6R antagonists is established , which might help discover potent and specific antagonists .

Aumento dos níveis do receptor solúvel da Interleucina-6 em pacientes com pré-eclâmpsia em relação a gestantes normotensas / Increased levels of the soluble receptor of interleukin-6 in patients withpreeclampsia compared to normotensive pregnant women

Objetivos: Comparar níveis plasmáticos do receptor solúvel da interleucina-6 (IL-6sR) entre gestantes normotensas e com pré-eclâmpsia.Métodos: Realizou-se coleta de sangue materno no período pré-parto de 21 pacientes com pré-eclâmpsia e 39 controles normotensas. As amostras foram armazenadas a menos 80°C até a análise laboratorial. Os níveis séricos de IL-6sR foram mensurados através do teste imunoenzimático ELISA. Para comparar os grupos foi utilizado teste t de Student. Consideraram-se significantes os resultados com P menor do que 0,05.Resultados: Os dados de gestantes com pré-eclâmpsia e gestantes normotensas, respectivamente, foram: idade materna 22,3±4,8 vs 26,0±3,7 anos (P=0,06); idade gestacional 32,7±5,8 vs 40,1±0,8 semanas (P=0,01); pressão arterial sistólica 143,0±2,2 vs 118,8±3,1 mmHg (P=0,01); pressão arterial diastólica 112,5±4,0 vs 77,2±10,2 mmHg (P=0,01); ácido úrico 5,87±1,10 vs 4,57±0,12 mg/dL (P=0,02); creatinina 0,82±0,12 vs 0,73±0,09 mg/dL (P=0,01); peso do recém-nascido 2.130,7±839,3 vs 3.555,0±261,0 gramas (P=0.01) e peso da placenta 621,3±167,0 vs 796,3±154,2 gramas (P=0,05).A relação proteinúria/creatininúria no grupo das pacientes com pré-eclâmpsia foi de 2,40±1,31. O valor de IL-6sR(ng/dL) na pré-eclâmpsia foi 28,7±10,8 vs 16,5±6,4 na gestante normotensa (P=0,01).Conclusões: Estes resultados mostram o aumento dos níveis plasmáticos do IL-6sR em pacientes com pré-eclâmpsia, em relação a gestantes normotensas. Mais estudos se mostram necessários para o esclarecimento da fisiopatologia desta entidade, como a análise de outras citocinas ligadas a esse receptor, visto que elas podem ser a chave para a resposta inflamatória sistêmica que ocorre nestas pacientes e, portanto, para o seu tratamento...

Aims: To compare Interleukin-6 soluble receptor (IL-6sR) plasmatic levels between normotensive pregnant controls and preeclamptic women.Methods: Maternal blood samples were collected before delivery from 21 patients with preeclampsia and 39 normotensive pregnant controls. Samples were stored at -80°C until laboratory assay. IL-6sR was measured by ELISA enzyme immunoassay. To compare groups Student's t test was used. Results with P less than 0.05 were considered significant.Results: Data from preeclampsia and normotensive pregnant controls were respectively: maternal age 22.3±4.8 vs 26.0±3.7 years (P=0.06); gestational age 32.7±5.8 vs 40.1±0.8 weeks (P=0.01); systolic blood pressure 143.0±2.2 vs 118.8±3.1 mmHg (P=0.01); diastolic blood pressure 112.5±4.0 vs 77.2±10.2 mmHg (P=0.01); uric acid 5.87±1.10 vs4.57±0.12 mg/dL (P=0.02); creatinine 0.82±0.12 vs 0.73±0.09 mg/dL (P=0.01); birth weight 2130.7±839.3 vs 3555.0±261.0 g (P=0.01); placental weight 621.3±167.0 vs 796.3±154.2 g (P=0,05). Proteinuria over creatininuria ratio in the preeclampsia group was 2.40±1.31. The concentration of IL-6sR (ng/dL) was 28.7±10.8 in preeclampsia vs 16.5±6.4 in normotensive pregnant controls (P=0.01).Conclusions: These results show an increased plasma levels of IL-6sRin patients with preeclampsia compared to normotensive pregnant women. More studies are necessary to clarify the pathophysiology of this entity, including the analysis of other cytokines linked to this receptor, due to the fact that they can be the key for the systemic inflammatory response that occurs in these patients and therefore for their treatment....