ABSTRACT
Objective:To investigate the role of serum CX3CR1 in the diagnosis of coronary artery stenosis and in the evaluation of prognosis after percutaneous coronary intervention.Methods:A total of 101 patients with coronary artery stenosis (≥ 50% stenosis) confirmed with coronary angiography (CAG) in Haiyang People's Hospital from January 2018 to May 2019 who were followed up till May 2021 were included in the observation group. Thirty-four healthy individuals who underwent physical examination during the same period were included in the control group. Patients in the observation group were divided into an in-stent restenosis group (ISR group, n = 28) and a non-ISR group ( n = 73). The expression of CX3CR1 was detected. The incidence of adverse cardiac events was calculated. The sensitivity, specificity, and area under the curve (AUC) plotted for the use of CX3CR1 to diagnose coronary artery stenosis and predict adverse cardiac events were evaluated. Results:The expression of CX3CR1 in the observation group was (3.95 ± 1.05) μg/L, which was significantly higher than (2.30 ± 0.65) μg/L in the control group ( t = 2.87, P < 0.05). The receiver operating characteristic curve analysis showed that the AUC, sensitivity, and specificity of the use of CX3CR1 in diagnosing coronary artery stenosis were 0.892, 75.2%, and 88.2%. The incidence of non-fatal myocardial infarction, angina pectoris, heart failure, and cardiac death in the ISR group was significantly higher compared with the non-ISR group ( χ2 = 8.06, 7.17, 8.06, 7.17, all P < 0.05). The receiver operating characteristic curve analysis results showed that the AUC value of CX3CR1 in predicting non-fatal myocardial infarction, angina pectoris, heart failure, and cardiac death were 0.786, 0.895, 0.997, and 0.887, respectively. Conclusion:CX3CR1 is highly expressed in coronary artery stenosis, which can provide a reference for the diagnosis and prognostic evaluation of coronary artery stenosis.
ABSTRACT
Objective:To investigate the clinical significance of cc-chemokine receptor 7 (CCR7) as a potential diagnostic or differential marker for chronic lymphocytic leukemia (CLL).Methods:A total number of 643 patients with B-cell chronic lymphoproliferative diseases (B-CLPD) admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled. The patients included 327 cases of CLL, 58 cases of mantle cell lymphoma (MCL), 34 cases of follicular lymphoma (FL), 36 cases of marginal zone lymphoma (MZL), 10 cases of hair-cell leukemia or its variants (HCL/HCLV-v), 40 cases of Waldorf′s macroglobulinemia (WM), 48 cases of CD5 +B-cell chronic lymphoproliferative disease unclassified (B-CLPD-U) and 90 cases of CD5 -B-CLPD-U. At the same time, 20 samples from healthy people from the medical examination center of our hospital were used as normal controls. Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients, and Fluorescence in situ hybridization (FISH) was used to analyze the genomic alterations: the ataxia telangiectasia mutant gene (ATM) deletion, the 13q14 deletion, the P53 deletion and trisomy 12. Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1 (SF3B1), NOTCH1, tumor protein 53 (TP53) and immunoglobulin heavy chain variable region (IGHV). Measurement data were compared by Mann-Whitney test, and the positive rates were compared by chi-square test. The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic (ROC) curve. Results:The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8% (257/283) and 84.1% (37/44), respectively, and there was no significant difference of the positive rates (χ 2=1.228, P=0.268) between groups. The positive expression rates of CCR7 in CLL, MCL, CD5 +B-CLPD-U, CD5 -B-CLPD-U, FL, WM, HCL/HCL-v and MZL were 89.9% (294/327), 10.3% (6/58), 6.3% (3/48), 8.9% (8/90), 0, 0, 0 and 13.9% (5/36) respectively, and the median mean fluorescence intensity (MFI) was 278 (246, 307), 114 (106, 128), 112 (106, 117), 110 (104, 121), 108 (105, 119), 111 (105, 124), 112 (108, 115) and 109 (105, 120) respectively. Compared with CLL, the positive expression rates of CCR7 in other types of B-CLPDs were lower significantly (χ 2=181.3, 177.8, 232, 164.7, 180.8, 62.6, 129, P<0.01). In addition, the sensitivity, specificity and accuracy of CCR7 for distinguishing CLL from other types of B-CLPD were 89.9%, 93.0% and 92.3%, respectively. The positive expression rate of CD49d in CCR7 +CLL patients was 13.9%, which was significantly lower than that in CCR7 -CLL patients (42.1%) (χ 2=7.6, P=0.01). The coincidence rate of 13q14 deletion was 50.3% in CCR7 +CLL patients, which was significantly higher than that in CCR7 -CLL patients (20%) (χ 2=6.56, P=0.01). Conclusions:The CC-chemokine receptor 7 (CCR7) antigen is an effective marker for the diagnosis and identification of chronic lymphocytic leukemia (CLL). The expression level of CCR7 in clinical specimens can distinguish CLL from other pathological subtypes of B-CLPDs.
ABSTRACT
Objective:To investigate the relationship between neutrophil chemotactic function and chemokine receptor in the early stage of deep second- and third-degree burns.Methods:Twenty patients with severe burns (burn group) who received treatment within 6 hours after burns in Yantai Yeda Hospital from January 2019 to June 2020 were included in this study. Twenty healthy controls (healthy group) who concurrently received physical examination in the same hospital were also included. The general data and laboratory examination indexes in each group were analyzed. The correlation between neutrophil chemotactic function and chemokine receptor was evaluated.Results:There were no significant differences in general data between the two groups (all P > 0.05). At 1, 3 and 5 days after admission, the number of neutrophils, the number of white blood cells, and procalcitonin, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor-α levels in the burn group were significantly higher than those in the healthy control groups ( F = 12.56, 13.45, 15.78, 17.83, 22.56, 13.39, 10.82, all P < 0.05). At 1, 3 and 5 days after admission, neutrophil migration distance in the burn group was (1 510.22 ± 108.45) μm, (1 380.90 ± 115.67) μm, (1 026.10 ± 95.48) μm, respectively, which were significantly shorter than (1 944.67 ± 139.20) μM in the healthy control group ( t = 23.44, 25.67, 27.52, all P < 0.05). At 5 days after admission, chemokine receptors 1 and 2 positive rates in the burn group were (47.40 ± 1.76)% and (75.33 ± 2.42)%, respectively, which were significantly lower than (95.24 ± 4.89)% and (97.78 ± 2.10)% in the healthy control groups ( t = 4.92, 5.67, both P < 0.05). Correlation analysis showed that neutrophil migration distance was positively correlated with chemokine receptor expression in patients with deep second- and third-degree burns ( r = 0.72, 0.61, both P < 0.05). Conclusion:Neutrophil chemotactic function and chemokine receptor expression decrease in the early stage of deep second- and third-degree burns.
ABSTRACT
Objective@#To investigate the correlation between CXC chemokine receptor 6 (CXCR6) and prognosis of renal clear cell carcinoma.@*Methods@#A total of 100 patients with renal clear cell carcinoma who underwent surgery in the First People's Hospital of Ziyang from January 2013 to October 2014 were selected. Immunohistochemistry was used to detect the expression of CXCR6 in 100 cases of renal clear cell carcinoma and adjacent normal tissues. The patients were followed up to observe the positive rate of CXCR6 expression and the factors affecting overall survival (OS) and progression-free survival (PFS) of renal clear cell carcinoma and adjacent normal tissues.@*Results@#The positive rate of CXCR6 expression in renal clear cell carcinoma tissues was higher than that in adjacent tissues, and the difference was statistically significant [46.0% (46/100) vs. 20.0% (20/100), χ2 = 15.287, P < 0.01]. The positive expression rate of CXCR6 in patients with clinical stage Ⅲ-Ⅳ, lymph node metastasis and pathological grade Ⅲ-Ⅳ was higher than that in patients with clinical stage Ⅰ- Ⅱ, pathological grade Ⅰ- Ⅱ and without lymph node metastasis, and the difference was statistically significant (all P < 0.05). A total of 92 patients were followed up and 40 died. The follow-up time reached to (35-60) months and the median follow-up time was 48.9 months. Kaplan-Meier and log-rank test showed that patients with positive CXCR6 expression had lower 3-year OS and PFS rate compared with patients with negative CXCR6 expression, and the difference was statistically significant (3-year OS rate: 52.1% vs. 78.6%, χ2 = 10.027, P = 0.001; 3-year PFS rate: 48.3% vs. 67.8%, χ2 = 4.344, P = 0.037). Cox regression multivariate analysis showed pathological grade (OS: OR = 2.154, 95% CI 1.547-9.517, P = 0.023; PFS: OR = 1.235, 95% CI 1.109-5.917, P = 0.042), lymph node metastasis (OS: OR = 1.412, 95% CI 1.109-5.917, P = 0.041; PFS: OR = 1.841, 95% CI 1.354-8.994, P = 0.010), CXCR6 expression (OS: OR = 1.864, 95% CI 1.358-6.813, P = 0.031; PFS: OR = 1.457, 95% CI 1.127-6.884,P = 0.025) were independent risk factors of OS and PFS for renal clear cell carcinoma patients treated by the surgery.@*Conclusions@#The positive expression of CXCR6 is an independent risk factor for OS and PFS of renal clear cell carcinoma. The prognosis of patients with positive CXCR6 expression is poor.
ABSTRACT
Objective To investigate the effect of irbesartan combined with resuvastatin on early diabetic nephropathy( DN) complicated with cardiovascular disease,and its influence on SDF -1/CXCR4 expression. Methods From January 2016 to December 2017,130 early DN patients complicated with cardiovascular disease in the Second People＇s Hospital of Linhai were selected as study objects,and according to the digital table,they were randomly divided into three groups: irbesartan group(control group 1,n＝43),resuvastatin group(control group 2,n＝43) and irbesartan combined with resuvastatin group (observation group,n＝44).The clinical efficacy,blood pres-sure,blood lipids and SDF -1/CXCR4 expression were compared among the three groups.Results After treatment,the total effective rate in the observation group was 93.18%(41/44 ),which in the control group 1 was 69.77%(30/43),which in the control group 2 was 74.42%(32/43),there was statistically significant difference among the three groups(χ2＝12.341,10.106,all P＜0.05).After treatment,the levels of SBP and DBP in the observation group had statistically significant differences compared with those in the control group 1 and control group 2( F＝23.087,20.249,all P＜0.05).After treatment,there were statistically significant differences in TC,TG,HDL-C and LDL-C between the observation group and control group 1,control group 2(F＝18.408,15.623,14.852,9.845,all P＜0.05).After treatment,the level of SDF -1 in the observation group was significantly higher than that before treatment,and which was also significantly higher than that in the control group 1 and control group 2(F＝21.085,P＜0.05).After treatment,the positive rate of CXCR4 in the observation group was significantly higher than that before treatment,and compared with that in the control group 1 and control group 2,the difference was statistically significant(F＝23.641,P＜0.05).Conclusion Irbesartan combined with resuvastatin in the treatment of early DN patients with cardiovascular disease has significant clinical efficacy,can effectively improve blood pressure and blood lipid levels,significantly improve the level of SDF -1 and CXCR4 positive rate.
ABSTRACT
Objective@#To explicit, the expression of chemokine receptor 3 in HCC tissues and its relationship with overall survival of patients, and to explore the effect of targeted silencing CXCR3 gene on proliferation of hepatocellular carcinoma cells and its mechanism of action.@*Methods@#The expression of CXCR3 in 60 cases of hepatocellular carcinoma and its adjacent tissues were detected by immunohistochemistry. The clinicopathological correlations between the expression levels of CXCR3 in hepatoma tissues of liver cancer patients were analyzed and univariate Kaplan-Meier survival analysis was performed in combination with follow-up data. Huh7 hepatoma cells were infected with lentivirus LV-CXCR3-shRNA. The effects of CXCR3 deletion on proliferation of hepatoma cells were determined by CCK-8 assay and tumor-bearing nude mice experiment.@*Results@#CXCR3 was highly expressed in HCC tissues, and the overall survival rate (OS) of patients with high CXCR3 expression was significantly lower than that of patients with low expression. After the CXCR3 gene was successfully silenced in Huh7 hepatocellular carcinoma cells, the proliferation ability of Huh7 cells was significantly inhibited in vitro, and the tumor growth rate of nude mice was slowed down, and the activity of JAK-STAT pathway in Huh7 cells was decreased, and the levels of c-MYC and Bcl-xl protein were decreased. In addition, deletion of CXCR3 can effectively inhibit IL-6-mediated JAK-STAT pathway activation.@*Conclusion@#CXCR3 high expression indicated that the survival rate was poor, and the target silencing of CXCR3 gene could inhibit the proliferation of hepatocellular carcinoma cells and maybe related to inhibition of JAK-STAT pathway activity. CXCR3 may be a potential target for the treatment of hepatocellular carcinoma.
ABSTRACT
Objective To investigate the role and mechanism of SDF-1/CXCR4 in the development of chronic rejection (CR) in rat models.Methods CR rat models were established using Fisher 344 to Lewis rats.In the blank control group (n=10),Lewis rats getting isotransplantation were treated with Cyclosporine A.CR rat models were established in positive group (n=10) and the rats were treated with Cyclosporine A.CR rat models were also established in CXCR4 antagonism group (n=10) and the rats were treated with both Cyclosporine A and AMD3100 (1 mg/kg).The serum creatinine levels were monitored every week.Kidney grafts were harvested 12 weeks after transplantation for histological analysis.We evaluated graft injuries using chronic allograft damage index (CADI) scores.Q-PCR and Western blotting were used to measure CXCR4,TGF-β1/Smad3 signaling pathway and α-smooth muscle actin (α-SMA) expression in renal allograft tissues.Results The serum creatinine levels in blank control group and CXCR4 antagonism group were significantly lower than those in positive control group (P<0.05).The blank control group and CXCR4 antagonism group presented milder pathological manifestations of CR.The CADI score in CXCR4 antagonism group was 3.54,which was lower than that of positive control group (P<0.05).The expression of biological markers in TGF-β1/Smad3 signaling pathway and SDF-1/CXCR4 signaling pathway was significantly lower in blank control group and CXCR4 antagonism group than in positive control group (P<0.05).Conclusion SDF-1/CXCR4 signaling pathway may play a crucial role in the development of CR.The usage of SDF-1/CXCR4 antagonist can protect renal allograft by inhibiting the TGF-β1/Smad3 pathway.Therefore,antagonism of CXCR4 may provide a novel way to prevent the development of CR.
ABSTRACT
Chemokines and chemokine receptors involve in biological activity and pathological process widely.It has been reported that many tumor cells overexpress functional chemokines.In lung cancer,chemo-kines involve in its proliferation,apoptosis,invasion and metastasis.Chemokines and chemokine receptor over-expressed in lung cancer can be used as specific target for pertinent anti-tumor treatment.
ABSTRACT
Objective To synthesize 628F-Py-AMD3465,to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell (A549).Methods AMD3465 quaternary ammonium salt precursor was directly labeled with 18F,then 628F-Py-AMD3465 was synthesized through nucleophilic reaction,hydrolysis,neutralization and the product was purified using HPLC.The labeling yield and radiochemical purity were analyzed by HPLC.Fifteen Kunming mice were injected with 5.55 MBq of 628F-Py-AMD3465 and sacrificed at 5,20,40,60 and 120 min postinjection.The selected tissues were harvested and weighed,and the radioactivity in the tissues was measured by an automated γ-spectrometer.The ％ID/g was calculated.MicroPET/CT studies were performed on A549-bearing mice after injecting 6-18F-Py-AMD3465 through vena caudal.Paired t test was used.Results 6-18F-Py-AMD3465 was successfully synthesized with the labeling yield of (9.0±2.0)％,the total synthesis time was about 60 min,and the radiochemical purity was more than 98％.Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice,which demonstrated that 6-18 F-Py-AMD3465 was mainly excreted through the kidneys.Biodistribution in A549-bearing mice was similar to that in normal mice.The tumor/muscle ratio at 40 min was 5.0,but the radiouptake of the tumor was still lower than that of the normal lung:(8.05±0.35) ％ID/g vs (9.33±0.66) ％ID/g;t=5.26,P＜0.05.MicroPET/CT imaging showed that the high-uptake location of 6-18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice,and the tumor uptake reached the maximum level at 45 min post-injection (SUV 0.67).Conclusions 6-18F-Py-AMD3465 can be synthesized by a simple method.A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer.
ABSTRACT
Objective To detect the expression levels of multiple serum chemokines including IFN-inducible T cell chemoattractant (ITAC),Fractalkine,macrophage inflammatory protein (MIP)-3α,IL-8,MIP-lα,MIP-1β in patients with lung cancer and explore their association with the clinical characteristics of lung cancer as well as the correlations among these chemokines.Methods Forty newly diagnosed patients with lung cancer and thirty healthy controls were enrolled for detection of the serum levels of 6 kinds of chemokines by Luminex technology.The correlations of clinical characteristics of lung cancer with these chemokines and the correlations among these chemokines were analyzed by SPSS 17.0 software.Results The serum levels [M (QR)] of IL-8,Fractalkine and MIP-3α in patients with lung cancer were 5.16 (4.74),128.45 (141.89),10.31 (8.88) respectively,and 2.01 (0.95),61.46 (74.81),8.08 (5.87) respectively in control group,with significant differences (Z =-4.783,P ＜0.001;Z =-4.046,P ＜0.001;Z =-3.105,P =0.002).The expression of MIP-1β in lung adenocarcinoma was significantly higher than that in squamous carcinoma [18.32 (12.27) vs.13.72 (7.31),Z =-2.212,P =0.027],and of ITAC in squamous carcinoma was significantly higher than that in small cell lung cancer [24.51 (22.48) vs.9.28 (4.85),Z =-2.460,P =0.014].The expressions of MIP-3α and Fractalkine were positively correlated in the two groups (r =0.619,P＜0.001;r=0.766,P＜0.001).Conclusion The expressions of IL-8,Fractalkine and MIP-3α increase significantly in lung cancer patients,and they are may play important roles in metastatic lung cancer.
ABSTRACT
Objective To investigate the chemokine 12 (CXCL12) and chemokine receptor 4 (CXCR4) expressions in hypopharyngeal carcinoma and its place in the disease development,invasion and metastasis of significance.Methods Immunohistochemistry was used to detect the expressions of CXCL12 and CXCR4 in 35 cases of hypopharyngeal cancer tissues and in 28 cases of tumor-adjacent non-tumor tissues.Results The expressions of CXCL12 and CXCR4 in the hypopharynx carcinomas were significantly higher (P ＜ 0.05).Both expressed in hypopharyngeal carcinomas was significantly positively correlated (P ＜ 0.01).Both hypopharynx cancer in lymph node metastasis group were significantly higher than the expression of cervical lymph node metastasis group,the difference was significant (P ＜ 0.05).Conclusions CXCL12 and CXCR4 are involved in hypopharynx cancer development,invasion and metastasis,and there is a positive feedback regulation mechanism between two factors.Moreover,CXCL12 and CXCR4 have synergistic effect in development,invasion and metastasis of hypopharynx cancers.
ABSTRACT
Background The pathogenesis and mechanism research of corneal neovascularization is of important significance for the prevention and management of corneal neovascularization.Some relative researches are being performed on non-corneal neovascularization-derived vascular endothelial cells, so the results are affected to a certain extent.Objective This study was to isolate and culture vascular endothelial cells from experimental corneal neovascularization tissue and detect the expression of chemokine receptors in vitro.Methods Corneal neovascularization models were established on 10 SPF male BALB/c mice with the age of 7-8 weeks by sticking the filter papers with NaOH on the central corneas, and then the immunofluorescence technique was use to assay the CD31 expression in corneal flatmount 2 weeks after modeling.Corneal pieces were made in 2 weeks after alkali burn and then were digested by collagenase type D.Vascular endothelial cells were isolated from neovascularized tissue by affinity purification using magnetic beads coated with anti-CD31.The cells were cultured on fibronectin-coated walls and then identified by immunocytochemistry.Reverse transcription-PCR was employed to detect the expressions of chemokine receptors in the cells.The use and care of the animals complied with ARVO Statement and this experimental procedure was approved by Soochow University Animal Care Committee.Results Corneal neovascularization occurred at 7 days and peaked at 2 weeks after modeling, and immunofluorescence exhibited the green network-like fluorescence for CD31 antibody in corneas.The cells grew against the wall 2 hours after culture with the polygon shape and large dimension, and the growth obviously quickened after passage.The cultured cells showed the positive response for CD31 antibody, showing the brown dye in cytoplasm,in contrast,the expression of CD31 was absent in corneal stromal cells.Chemokine receptors were positively expressed in the cells with the strongest expression levels in CCR1 ,CCR2,CCR3 and CCR4 mRNA and the weakest expression levels in CCR9,CXCR4 and CXCR5 mRNA,while CXCR3, CCR6, CCR10 and CX3CR1 mRNA were expressed with the moderate intensity.Conclusions Vascular endothelial cells can be obtained from experimental neovascularized corneas by affinity purification and express chemokine receptors,which facilitate the study of their biological properties.
ABSTRACT
Objective To investigate the relationship of the interaction between age and polymorphisms of E-selectin gene A561C, chemokine receptor CCR2 gene A190G with the susceptibility, invasion and metastasis of gastric carcinoma.Methods Based on tumor-node-metastasis (TNM) staging classification, 750 patients with confirmed gastric carcinoma in our hospital from December 2011 to November 2014 were divided into 5 groups: stage Ⅰ, stage Ⅱ , stage Ⅲ, stage Ⅳ and stage 0 (n=150, each).No significant difference was observed in gender, ethnicity, birthplace and living habits among the 5 groups.Meanwhile, 750 healthy controls were selected in this study during the same time, and there was no significant difference in gender, ethnicity and birthplace between the healthy controls and patients with gastric carcinoma.The genetic polymorphisms of E-selectin gene A561C and chemokine receptor CCR2 gene A190G were analyzed by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in peripheral blood mononuclear cells (PBMs).Results The frequencies of CC (A561C) and GG (A190G) genotypes were 56.5％ and 56.8％ respectively in gastric carcinoma cases and 22.8％ and 23.1％ respectively in healthy controls, with statistically significant differences in the distribution frequencies between the two groups (P＜0.01 for all).The risk for gastric carcinoma significantly increased in subjects with CC (A561C) genotype (OR=4.4038, 95％CI=2.9421-7.2397) and in GG (190A/G) genotype (OR=4.3852, 95％ CI =2.8207-7.4942).Combined analysis of the polymorphisms showed that the distribution frequency of CC (A561C) genotype / GG (190A/G) genotype in gastric carcinoma cases and healthy controls was 46.4％ and 11.9％ respectively (P＜0.01).The positive interactions of age with CC (A561C) genotype and GG (190A/G) genotype for the risk of invasion and metastasis of gastric carcinoma were found (γ＞1 for both).The distribution frequencies of CC (A561C) genotype and GG (190A/G) genotype were 50.0％ and 50.0％ in stage Ⅰ , 63.4％ and 64.0％ in stage Ⅱ ,69.3％ and 69.3％ in stage Ⅲ, 76.7％ and 77.3％ in stage Ⅳ, and 23.3％ and 23.3％ in stage 0 respectively.Statistically significant differences were found in the distribution frequencies between stage 0 and the other 4 stages (P＜0.01 for all).The risks for the invasion and metastasis of gastric carcinoma were significantly increased in subjects with CC (A561C) genotype (ORⅠ-Ⅳ =3.2857-10.7959) and in those with GG (190A/G) genotype (ORⅠ-Ⅳ =3.2857-11.2101).Combined analysis of the polymorphisms showed that distribution frequency of CC (A561C) genotype / GG (190A/G) genotype had significant differences between the stage Ⅰ ～Ⅳ and stage 0 (39.3％, 53.3％, 59.3％,68.0％ vs.12.0％, P＜0.01).The proportion of elderly subjects were higher in Grade Ⅰ ～Ⅳ than in Grade 0 (51.3％, 62.7％, 70.0％, 75.3％ vs.26.7％, P＜0.01 for all).The risk for invasion and metastasis of gastric carcinoma was significantly increased in elderly patients (ORⅠ-Ⅳ =2.9001 ～8.3986).The positive interactions of age with CC (A561C) genotype and GG (190A/G) genotype for the risk of invasion and metastasis of gastric carcinoma were found (γ＞ 1 for All).Conclusions Age and E-selectin gene A561C (CC) and chemokine receptor CCR2 gene A190G (GG) are the risk factors for the invasion and metastasis of gastric carcinoma, and the interactions between age and genetic polymorphisms increase the risk of invasion and metastasis of gastric carcinoma.
ABSTRACT
Background Graft rejection is a primary cause of corneal transplantation failure,especially in high-risk keratoplasty.How to extend the survival time of graft is a problem to be solved.Objective This study was to investigate the influence of immune tolerance on high-risk rat keratoplasty induced by donor bone marrowderived immature dendritic cells (imDCs) transfected by chemokine receptor 7 (CCR7) recombinant adenovirus (Ad).Methods Bone marrow-derived imDCs were isolated and cultured from femur marrow of one male Wistar donor rat.The cells were transfected using recombinant Ad vector with rat CCR7 gene and resuspended in 500 μl PBS containing 1％ fetal bovine serum with the cells 1 × 107.High-risk corneal transplantaion models were established using monolateral corneal alkali-burn method in 60 SD rat recipients, and then allograft keratoplasty was performed with the 30 Wistar rats as donors.The models were randomized into the PBS group,imDCs group,imDCs with blank Ad vector group and imDCs with Ad-CCR7 group following the corresponding solution injection via caudal vein on preoperative day 7 and postoperative day 3 respectively.The survival time of graft was evaluated under the slit lamp microscope once per day.On the 14th day after operation, corneal sections were prepared from 6 eyes of each group for the pathological examination,and the relative expression levels of T helper cell 1 (Th1)-related factors,interleukin-2 (IL-2) mRNA and interferon-γ(IFN-γ) mRNA,as well as Th2-related factors, IL-4 mRNA and IL-10 mRNA, were detected by reverse transcription PCR (RT-PCR).The use and care of animals complied with the ARVO statement Results The mean survival time of grafts was (10.44±1.88) , (16.00±2.18) , (15.11±2.03) and(23.67±2.83) days in the PBS group,imDCs group,imDCs with blank Ad group and imDCs with Ad-CCR7 group, respectively, with a significant difference among the 4 groups (F =53.005, P =0.000).Compared with the PBS group, the mean survival time of grafts was considerably extended in the imDCs group,imDCs with blank Ad group and imDCs with Ad-CCR7 group (t=5.220,4.385,12.423 ,all at P=0.000) ,and a remarkble prolongation of graft survival duration was seen in the imDCs with Ad-CCR7 group in comparison with the imDCs group and the imDCs with blank Ad group (t =7.204,8.039,both at P=0.000).The relative expression levels of IFN-γ mRNA and IL-2 mRNA in the grafts were significantly lower,but the relative expression levels of IL-4 mRNA and IL-10 mRNA were significantly higher in the imDCs group,imDCs with blank Ad group and the imDCs with Ad-CCR7 group than those in the PBS group (all at P＜0.05).Compared with the imDCs group and the imDCs with blank Ad group, the relative expression levels of IFN-γ mRNA and IL-2 mRNA in the grafts were remarkably delined,but the relative expression levels of IL-4 mRNA and IL-10 mRNA were remarkably elevated in the imDCs with Ad-CCR7 group (all at P =0.000).Conclusions Application of imDCs transfected with CCR7 recombinant Ad via vena caudalis can prolong the survival time of grafts after keratoplasty of SD rats probably by affecting the balance of Th1/Th2 cytokines.
ABSTRACT
Objective Through detecting the expression of chemokine CCL21 and its receptor CCR7 in thyroiditis of NOD mice induced by excessive iodine and thyroglobulin (Tg) immunization,to explore the mechanism of lymphocytic infiltration.Methods Seven to eight weeks old female NOD (non-obese diabetic) mice were used,the mice were divided into four groups by random number table,7 mice for each group.Control group:intoke distilled water;,Tg group:intoke'distilled water,use pig Tg emulsified in Freund's complete adjuvant subcutaneous injection to immunization,0.10 mg Tg for each mouse at 8 weeks old,strengthened immunity at 11 and 15 weeks old (0.05 mg Tg for each mouse,and emulsified by Freund's incomplete adjuvant); iodine excess (HI) group:intoke 0.05％ NaI water; iodine excess combined with Tg (HI + Tg) group:intoke 0.05％ NaI water,Tg immunization method was same to Tg group; all mice were raised in specific pathogen free (SPF) environment.All mice were executed at 16 weeks old,and removed the thyroid tissue.Morphologic change in thyroid was observed by HE staining.Immunofluorescence (IF) staining was used to observe CD3,CD22,CCL21 and CCR7 expression in thyroid.Real-time PCR was used to detect CCL21 mRNA expression in thyroid.Results The morphologic change of thyroid was observed under the light microscope,in HI group,thyroid follicle distended,colloid accumulation,lymphocytes accumulate together and disorganization was seen; Tg group thyroid had scatted lymphocytes; HI + Tg group enhanced inflammation response and disorganization.IF staining showed that lymphocytes infiltrated in thyroid were almost CD3+ T cells,only few scatted CD22+ B cells; CCL21 and CCR7 were negative in control group,CCR7 positive cells were scatted in Tg group but no CCL21 expression,in HI and HI + Tg groups,we could see CCL21 strong positive expression in inflammation area and also had CCR7 positive cells there.CCL21 mRNA relative expression in thyroid:Tg group (3.20 ± 0.18),HI group (1.72 ± 0.31),and HI ± Tg group (9.94 ± 0.32) increased compared to control group (1.00 ± 0.17,all P ＜ 0.01).Conclusion CCL21 and its receptor CCR7 have improved lymphocytic infiltration in autoimmune thyroiditis
ABSTRACT
Chemokine CCL18 plays significant roles in immune regulation by recruiting of inflammatory cells,which involves in immune and inflammatory processes.CCL18 protein is overexpressed in the serum of patients with cancer and some tumor tissues.However,it is still controversial that CCL18 plays the role of tumor promoter or tumor suppressor.Researches on the roles and mechanisms of CCL18 can provide new target for diagnosis and treatment of cancer.
ABSTRACT
BACKGROUND:The biological axis of CXC chemokine ligand 12 (CXCL12)/CXC chemokine receptor 4 (CXCR4) plays an important role in the specific metastasis of tumors, whereas the mRNA expression of glycoprotein hormone receptor 5, a stem cellmarker, exerts an important effects on tumor proliferation, invasion and metastasis. OBJECTIVE:To investigate the expressions of CXCL12/CXCR4 and glycoprotein hormone receptor 5 in human colorectal cancer tissues as wel as their relationship with clinical and pathological characteristics. METHODS:Totaly 100 colorectal cancer patients admitted at Liaoning Cancer Hospital & Institute from January to June 2013 were enroled as experimental group, and another 100 healthy volunteers served as control group. Immunohistochemical SP method was used to detect the expression of CXCL12, CXCR4 and glycoprotein hormone receptor 5 mRNA in human colorectal cancer tissues. We analyzed the correlation of CXCL12, CXCR4 and glycoprotein hormone receptor 5 mRNA expression with colorectal cancer patients’ age, sex, tumor size and site, lymphatic metastasis and prognosis . RESULTS AND CONCLUSION:There was a higher expression of CXCR4 and glycoprotein hormone receptor 5 mRNA, but lower expression of CXCL12 mRNA in the human colorectal cancer tissues. The mRNA expression of CXCR4, CXCL12 and glycoprotein hormone receptor 5 showed no correlation with age, gender, tumor size and site of colorectal cancer patients, but was related to lymphatic metastasis. For colorectal cancer patients with lymphatic metastasis, the expression of CXCR4 and glycoprotein hormone receptor 5 mRNA was higher, but no change was found in the expression of CXCL12 mRNA. The expression of CXCR4 was increased with the degree of tumor malignancy as wel as glycoprotein hormone receptor 5 expressed on the surface of gastrointestinal cancer and brain tumor stem cels. These findings indicate that the growth and metastasis of human colorectal cancer tissues are promoted by increasing the expression of CXCR4 and glycoprotein hormone receptor 5 in human colorectal cancer tissues; the CXCL12/CXCR4 biological axis and glycoprotein hormone receptor 5 are expected to become a new target therapy for tumor diagnosis and treatment.
ABSTRACT
Objective To explore the association of lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1),CX3C chemokine receptor 1 (CX3CR1) with coronary artery stenosis disease and its outcomes.Methods A case-control study was conducted.A total of 176 cases of coronary artery stenosis which were confirmed coronary artery stenosis ≥ 50％ by coronary angiography(CAG) were served as case group from department of cardiology of TEDA International Cardiovascular Hospital of Tianjin from May 2011 to April 2013.A total of 129 patients without coronary artery lesion by CAG from this hospital in the same period were served as control group,which has no history of heart disease,liver and kidney dysfuction,brain disease,hematological disease,other disorders that could bring out atherosclerosis and thrombosis.General information and laboratory parameters,LOX-1,CX3CR1,uric acid (UA) and creatinine (CREA) were measured in 2 groups.These parameters of each group were compared,the levels of LOX-1 and CX3CR1 in one-vessel stenosis were compared than that in multi-vessels stenosis in case group,the correlations between LOX-1,CX3CR1 and Gensini score and other variables were analyzed.Comparison of the levels of LOX-1 and CX3CR1 between major adverse cardiovascular events (MACEs) group and nonmajor adverse cardiovascular event (MACE) group was made during follow up 1.5 years.MACEs in patients with different levels of LOX-1 and CX3CR1 were compared during 1.5-year follow up.All of the data were analyzed by SPSS 16.0 software.The independent-samples T test,Mann-Whitney U test,Chi-square test,Spearman correlation,Binary Logistic Regression and Kaplan-Meier probability were adopted for data analysis.Results Comparison between case group and control group,LOX-1:3.72 (1.44,8.15) μg/L vs 0.75(0.50,1.19) μg/L,z =11.072,P ＜0.001 ;CX3CR1:(2.82 ± 1.85) μg/L vs (2.32 ±0.79) μg/L,t =2.021,P ＜ 0.05 ; UA:(351.34 ± 94.82) μmol/L vs (326.74 ± 79.51) μmol/L,t =2.094,P ＜ 0.05 ;CREA:(70.86 ± 20.94) μmol/L vs (65.55 ± 12.96) μmol/L,t =2.077,P ＜ 0.05.CX3CR1 level was significantly higher in patients with multi-vessels stenosis (2.84 ± 1.78) μg/L than that in one-vessel stenosis(2.48 ± 1.64) μg/L,there was significance in difference (t =2.207,P ＜ 0.05).There were no statistically significant correlation between LOX-1,CX3CR1 and Gensini score (R was 0.032,0.079 respectively,P＞ 0.05).LOX-1 was negatively related to left ventricular ejection fraction(LVEF) (R =-0.272,P ＜ 0.01),but positively related to left ventricular end-diastolic diameter (LVDD)(R =0.190,P＜0.05),positively related to UA (R =0.121,P ＜ 0.05).Comparison between MACE group and nonMACE group,LOX-1:7.38(4.97,11.88)μg/L vs 3.52(1.45,7.75) μg/L,z =2.762,P ＜0.01;CX3CRl:(4.02 ±2.90) μg/L vs (2.67 ± 1.48) μg/L,t =3.086,P ＜0.01.LOX-1 and TG were independent risk effects of coronary artery stenosis disease.MACEs were increased in patients with high levels of LOX-1 after PCI during following up 1.5 years (comparison between high-LOX-1 group and lowLOX-1 group,the probability of non-MACE was 87.1％ (115/132) vs 97.7％ (43/44),Log-ranK test,x2 =6.957,P ＜ 0.01).Conclusions LOX-1 and CX3CR1 may be involved in the process of coronary artery stenosis,and a high level of LOX-1 may be associated with left ventricular systolic dysfunction in patients with coronary artery stenosis.Elevated LOX-1 level are closely related to afterwards MACE incidence after PCI in patients with coronary artery stenosis.
ABSTRACT
BACKGROUND:The mechanisms of mesenchymal stem cells directional y homing to infarcted myocardium post myocardial infarction are stil unclear. OBJECTIVE:To investigate the role of stromal cellderived factor-1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis on mesenchymal stem cellmigration promoted by mononuclear cells after myocardial infarction. METHODS:Cardiomyocytes and mesenchymal stem cells were respectively isolated from suckling and adult Sprague-Dawley rats. Twelve healthy Sprague-Dawley rats were selected (six rats for myocardial infarction models and six for sham models), then circulating mononuclear cells were isolated. 4,6-Diamino-2-phenyl indole-labeled mesenchymal stem cells, cardiomyocytes and mononuclear cells were cultured into the upper, middle and lower layers of the tri-chamber coculture system, respectively. In this experiment, there were four groups:myocardial infarction group, AMD3100 (CXCR4 inhibitor) group, sham group and blank control group. After 48 hours, the number of migrating mesenchymal stem cells with blue-lighting nucleus was calculated under fluoroscope. Immunocytochemistry and immunofluorescent staining was used to detect SDF-1 expression in cardiomyocytes and CXCR4 expression in mesenchymal stem cells, respectively. RESULTS AND CONCLUSION:Migrating mesenchymal stem cells with positive expression of CXCR4 were observed in each group other than the blank control group. The number of migrating mesenchymal stem cells was higher in the myocardial infarction group than in the other groups. Tumor necrosis factor-αneutralizing antibody and CXCR4 inhibitor AMD3100 could obviously reduce the number of migrating mesenchymal stem cells (P<0.05). Cardiomyocytes in each group expressed SDF-1 positively. The gray values of SDF-1 expression in the myocardial infarction and AMD3100 groups were significantly higher than those in the sham and blank control groups (P<0.05). SDF-1/CXCR4 axis plays a certain role in mesenchymal stem cells migration promoted by mononuclear cells after myocardial infarction.
ABSTRACT
Objective To quantify the percentage of CD8+ T cells and their expressions of cytotoxic molecules and homing-related chemokine receptors in peripheral blood from patients with atopic dermatitis (AD).Methods Peripheral blood was obtained from 15 patients with AD and 14 healthy controls.Flow cytometric analysis was performed to determine the percentages of CD8+ T cells and CD8+CLA+ T cells in the peripheral blood samples,as well as the expression levels of cytotoxic molecules and homing-related chemokine receptors on these cells.Differences in these parameters were analyzed using t test,and relationship between these parameters was evaluated using Pearson correlation coefficient.Results No significant difference was observed between the patients with AD and healthy controls in the percentage of CD8+ T cells,the expressions of perforin,granzyme B,CCR10,CCR6 or FasL on CD8+ T cells,or the expressions of CCR4,CCR10,CXCR6 or FasL on CLA+CD8+ T cells (all P ＞ 0.05).A significant increase was noted in the percentage of CLA+CD8+ T cells (3.80％ ± 1.46％ vs.2.18％ ± 0.85％,t =3.636,P ＜ 0.01) and expression rates of CCR4 on CD8+ T cells (13.86％ ± 4.42％ vs.9.50％ ± 2.14％,t =3.738,P ＜ 0.01) as well as perforin and granzyme B on CLA+CD8+ T cells (74.27％ ± 15.94％ vs.57.20％ ± 14.64％,t =2.998,P ＜ 0.01; 70.90％ ± 13.85％ vs.56.41％ ± 11.00％,t =3.104,P ＜ 0.01) in the patients with AD compared with the healthy controls.Conclusions The proportion of CLA+CD8+ T cells is increased with enhanced expressions of cytotoxic molecules such as perforin and granzyme B in peripheral blood of patients with AD,which may contribute to the pathogenesis of AD.