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SUMMARY OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.
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Objective:To investigate the correlation between serum CXCL12 and the outcomes after intravenous thrombolytic therapy in patients with acute ischemic stroke.Methods:Consecutve patients with acute ischemic stroke treated with intravenous thrombolytic therapy in the Department of Neurology, the First Affiliated Hospital of Soochow University from January 1, 2020 to August 31, 2021 were enrolled retrospectively. Serum CXCL12 was measured by enzyme-linked immunosorbent assay within 24 h of onset. No improvement in early neurological function was defined as the National Institutes of Health Stroke Scale (NIHSS) 24 h after thrombolysis decreased by <4 compared with the baseline. The clinical outcome was evaluated by the modified Rankin Scale at 90 d after onset, and >2 were defined as a poor outcome. Multivariate logistic regression analysis was used to evaluate the correlation between serum CXCL12 and the outcome after intravenous thrombolysis, and the predictive value of serum CXCL12 for no improvement of early neurological function and poor short-term outcome was analyzed by the receiver operating characteristic (ROC) curve. Results:A total of 66 patients were enrolled, and the serum CXCL12 was 15.72±6.52 g/L. Twenty-seven patients (40.9%) had poor outcomes, and 34 (51.5%) had no improvement in early neurological function. Multivariate logistic regression analysis showed that higher serum CXCL12 was an independent predictor of poor outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.093-1.419; P=0.001) and no improvement in early neurological function ( OR 1.250, 95% CI 1.100-1.420; P=0.001). ROC curve analysis showed that the area under the curve of serum CXCL12 for predicting poor outcome was 0.793 (95% CI 0.679-0.908), the best cut-off value was 15.38 μg/L, and the corresponding sensitivity and specificity were 81.5% and 76.9%, respectively. The area under the curve of serum CXCL12 for predicting no improvement of early neurological function was 0.849 (95% CI 0.748-0.951), and the best cut-off value was 15.68 μg/L, and the corresponding sensitivity and specificity were 76.5% and 87.5%, respectively. Conclusion:Serum CXCL12 had a better predictive value for the outcomes of patients with acute ischemic stroke after intravenous thrombolytic therapy.
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Objective To detect the expression and clinical significance of stro-mal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in peripheral blood of patients with hepatitis C cirrhosis.Methods From January 2015 to January 2018,120 patients with hepatitis C cirrhosis in our hospital were selected as the subjects,including 60 patients with compensated hepatitis C cirrhosis and 60 patients with decompensated hepatitis C cirrhosis,and 60 hepatitis C patients without cirrhosis in the same period were selected as the control group.Enzyme linked immunosorbent assay (ELISA) was used to detect the expression levels of SDF-1 and CXCR4 in peripheral blood;the correlation between SDF-1 and CXCR4 expressions in compensated cirrhosis and decompensated cirrhosis patients was analyzed.Results The expression levels of SDF-1 and CXCR4 in peripheral blood samples of patients with decompensated cirrhosis of hepatitis C were significantly higher than those of patients with compensated cirrhosis of hepatitis C (P ＜ 0.05);the expression levels of SDF-1 and CXCR4 in peripheral blood samples of patients with compensated and decompensated cirrhosis of hepatitis C were significantly higher than those of control group (P ＜ 0.05);the expressions of SDF-1 and CXCR4 in peripheral blood of patients with compensated and decompensated cirrhosis of hepatitis C were positively correlated (r =0.684,P ＜ 0.05,r =0.765,P ＜ 0.05).Albumin (AlB) level in peripheral blood of cirrhosis group was significantly lower than that of control group (P ＜ 0.05);alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBIL),while fasting insulin (FINs) and interleukin (IL)-6 in cirrhosis group were higher than those of control group (P ＜ 0.05);SDF-1 level and CXCR4 level were positively correlated with AlB,FINs and IL-6 (P ＜ 0.05);multiple regression analysis showed that FINs,IL-6,SDF-1 and CXCR4 were risk factors for hepatitis C cirrhosis.Conclusions The levels of SDF-1 and CXCR4 in peripheral blood of patients with hepatitis C cirrhosis increased,and the levels of SDF-1 and CXCR4 in peripheral blood were positively correlated,suggesting that they may be involved in the regulation of the occurrence and development of hepatitis C cirrhosis.
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BACKGROUND: Nowadays, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis has been used extensively because of its biological effects and particularly a great progress has been achieved in the mechanism of SDF-1/CXCR4 signal axis as well as in its use for tissue regeneration. OBJECTIVE: To summarize the factors affecting the regulation of SDF-1 and CXCR4 and to review the research progress in the biological characteristics of SDF-1/CXCR4 signal axis. METHODS: The first author searched the PubMed, CNKI, WanFang and VIP databases for relevant articles published from January 1990 to August 2018. The keywords were "tissue engineering; cell homing; chemokine; regeneration; pulp regeneration; HIF-1; SDF-1; CXCL12; CXCR4; NOX-A12" in both Chinese and English. RESULTS AND CONCLUSION: Hypoxia-inducible factor-1 plays a key role in the regulation of SDF-1, and there are multiple factors which can affect the expression of CXCR4. SDF-1/CXCR4 signal axis formed by the combination of SDF-1 and CXCR4 plays an important biological role in various physiological and pathological processes. Blocking SDF-1 is used to inhibit the pathogenic effect of the SDF-1/CXCR4 signal axis for therapeutic purposes, while increasing SDF-1 can strengthen the SDF-1/CXCR4 signal axis and enhance the ability of chemotactic endogenous cell homing for tissue regeneration. To further illustrate the mechanism of the SDF-1/CXCR4 signal axis, we upregulate or downregulate the expression of SDF-1 or CXCR4 by exogenous means to influence the biological function of the signal axis, and thus provide theoretical basis for optimizing clinical treatment strategies, and developing the biological function of the signal axis for human health benefits.
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Chemokines and their receptors play an important role in the occurance and development of hepatocellular carcinoma(HCC).The effects of chemokines and their receptors in HCC are different,chemokines and their receptors associated with HCC are mostly expressed in promoting tumor cell proliferation,angiogenesis and invasion,but some chemokines and their receptors play an anti-tumor role.This reviews focus on the role of chemokines and their receptors in HCC.
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Objective To explore the relationship of chemokines CXCL10-135G/A and CXCL12 -801G/A gene polymorphisms with susceptibility to tuberculosis. Methods CXCL10-135G/A and CXCL12-801G/A polymorphisms of 102 tuberculosis patients(case group)and 115 healthy controls(control group)were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the relationship between the two polymorphisms and susceptibility to tuberculosis were analyzed. Results The genotype analysis of CXCL10-135G/A and CXCL12-801G/A was in accord with the law of Hardy-Weinberg equilibrium in the case group and the control group. The differences of genotype and allele distribution frequency of CXCL10-135G/A were statistically significant between the case group and the control group(all P<0.05).The frequency of G allele distribution was higher in the case group than that in the control group, and the frequency of A allele distribution was lower than that in the control group.There were no significant differences in genotype and allele distribution frequency of CXCL12-801G/A polymorphism between the case group and the control group (all P>0.05).Conclusion Chemokine CXCL10-135G/A gene polymorphism is associated with susceptibility to pulmonary tuberculosis,and CXCL12-801G/A gene polymorphism may not be associated with tuberculosis infection.
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Objective To investigate the mechanism and function of chemokine receptor CXCR4 and its ligand CXCL12 (CXCL12 / CXCR4) in primary hepatocellular carcinoma (PHC). Methods Western blot assay, immunohistochemistry and Real-time PCR were used to detect the protein and mRNA expressions of CXCL12/CXCR4 in 60 PHC and corresponding paracancerous tissue samples. Four kinds of hepatoma cells (Huh7, MHCC97h, HepG2 and Hep3B) and normal hepatocytes (7702) were routinely cultured, and then real-time PCR was performed to detect the mRNA expressions of CXCL12/CXCR4 in these cells to screen suitable experimental cells. CXCR4 interference plasmid (sh-CXCR4) and corresponding empty vector (sh-control) were transfected into MHCC97h to construct stable transfected cell lines. The ability of invasion, migration, and proliferation of the 2 groups of cells were detected by Tanswell invasion experiment, cell scratch test and MTT test. The stably expressed sh-control and sh-CXCR4 MHCC97h cells were taken into the subcutaneous of six nude mice, and the growth of the tumor was observed. Western blot assay was used to detect the expressions of vascular endothelial growth factor-C (VEGF-C) in sh-control and sh-CXCR4 MHCC97h cell lines and corresponding xenografts in nude mice, as the same in MHCC97h, which was transfected with CXCR overexpressed plasmid. Results (1) The results of Western blot assay, immunohistochemistry and Real-time PCR showed that the expressions of CXCL12/CXCR4 protein and mRNA were significantly higher in liver cancer tissues than those of paracancerous tissues. (2) The expression levels of CXCL12/CXCR4 mRNA were higher in Huh7, MHCC97h, HepG2 and Hep3B cells than those of 7702 cells. MHCC97h was selected as the experimental cells. The ability of invasion, migration and proliferation of MHCC97h cells transfected with sh-CXCR4 were significantly lower than those of sh-control group. Meanwhile, the growth rate of nude mice transplanted with sh-CXCR4 MHCC97h cells was also significantly lower than that of sh-control group. (3) Both in vitro and in vivo experiments showed that the expression of VEGF-C was lower in sh-CXCR4 group than that in sh-control group, and the expression of VEGF-C was obviously up-regulated after overexpression of CXCR4. Conclusion High expressions of CXCL12/CXCR4 are found in primary cancer tissues and hepatoma cells. CXCL12/CXCR4 may inhibit the proliferation and invasion of hepatoma cells by regulating the expression of VEGF-C protein.
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Objective To investigate the expression of CXCR4 and CXCL12 in the labial gland of patients with primary Sj?gren's syndrome (pSS), and to explore their role in the pathogenesis of pSS. Methods The expression of CXCR4 and CXCL12 in labial gland tissues was detected by immunohistochemistry in 32 cases of newly diagnosed pSS and 30 cases of oral mucosa cysts or trauma patients. The expression level, intensity and location were analyzed and compared statistically. χ2 test and Spearman correlation analysis were used for statistical analysis. Results The positive rate of CXCR4 in the test group was 91%(n=29), which was significantly higher than that in the control group (33%, n=10, χ2=21.77, P=0.001). The positive rate of CXCL12 in the test group was 97%(n=31), which was significantly higher than that in the control group 40%(n=12), and the difference was statistically significant ( χ2=23.57, P=0.001). Conclusion CXCR4 and CXCL12 are highly expressed in labial gland of pSS patients, this suggests that they participate in the pathological process of pSS local inflammatory response and play an important role in pSS pathogenesis.
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Objective@#To explore the mechanism of ibrutinib on drug resistance diffuse large B-cell lymphoma (DLBCL) cells.@*Methods@#DLBCL cell line was cultured with mesenchymal stem cells (MSC) , and DLBCL cells which migrated and adhered to MSC under microscope was counted. The secretion of CXCL12 by MSC were measured by ELISA. The expression of CXCR4 on DLBCL cells were measured by flow cytometry, HBL-1 cells were transfected with a CXCR4-lentivector. An Annexin Ⅴ-binding assay was used to detect the induction of apoptosis. Clonogenic growth of DLBCL cells was evaluated on MethoCult media. Ibrutinib was injected into NOD/SCID mice, tumor growth was assessed via caliper measurements every 3 days.@*Results@#MSC promoted migration and adhesion of DLBCL cells to MSC. Ibrutinib inhibited migration and adhesion of DLBCL cells to MSC in a dose-dependent manner (P<0.05) . CXCL12 secreted by MSC and CXCR4 expressed on DLBCL cells could induce each other, which upgraded the levels of secretion and expression. Ibrutinib could inhibit the secretion of CXCL12 (SUDHL10: 660 pg/ml vs 1 400 pg/ml, P=0.004; HBL-1: 720 pg/ml vs 1 490 pg/ml, P=0.018; DLBCL:850 pg/ml vs 1 450 pg/ml, P=0.004) and expression of CXCR4 (P<0.05) . When co-cultured with MSC, the ratio of HBL-1 cells apoptosis in the group of control, mitoxantrone, ibrutinib, mitoxantrone+ibrutinib were respectively 15.1%, 17.5%, 23.5%, 58.7%. After transfected with a CXCR4-lentivector and overexpressed CXCR4, the ratios of HBL-1 cells apoptosis were 14.2%, 16.1%, 22.5%, 38.3% respectively. The ratio of DLBCL cells apoptosis induced by mitoxantrone was lower when co-cultured with MSC (P<0.05) . But with the addition of ibrutinib, the ratio of apoptosis was increaed and it was similar to cultivation without MSC, which suggested ibrutinib could inhibit drug-resistance induced by MSC. But after transfected with a CXCR4-lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis was significantly lower when co-cultured with MSC which demonstrated that ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4. MSC enhanced lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. The number of colonies of control, MSC, Ibrutinib, MSC+Ibrutinib were 113±5, 205±4, 62±9, 123±3 (2.5×103/well, ±s) , respectively. The tumor volume of NOD/SCID mice were respectively 6 500, 17 000, 4 000, 10 000 mm3. Ibrutinib inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vitro.@*Conclusion@#Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of CXCR4 and inhibited MSC-mediated drug resistance. Ibrutinib also inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. These results provided a scientific rationality for relapsed/refractory DLBCL treatment with ibrutinib.
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Objective:To explore relationship among serum levels of adipocyte fatty acid binding protein (A-FABP), chemokine CXCL12 and acute ischemic stroke (AIS).Methods:A total of 92 aged AIS patients treated in our hospi-tal were selected as AIS group,another 83 healthy subjects undergoing physical examination in our hospital were en-rolled as healthy control group.Serum levels of A-FABP and chemokine CXCL12 were measured and compared be-tween two groups;United states national institutes of health stroke score (NIHSS)was used to assess neurological function deficit degree;Glasgow coma scale (GCS)was used to judge their consciousness.AIS patients were fol-lowed up for three months,then modified Rankin rating score (mRS)was used to assess their prognosis.Results:Compared with healthy control group,there were significant rise in serum levels of A-FABP [(20.92±2.63)μg/L vs.(35.63±5.72)μg/L]and chemokine CXCL12 [(4.25 ±0.61 )ng/ml vs.(24.31 ±3.46)ng/ml]in AIS group,P =0.001 both.Compared with small-medium size infraction group,NIHSS score≤15 scores group,GCS score≤8 scores group and good prognosis group,the levels of FABP [(32.89±5.34)μg/L,(31.72±4.15)μg/L, (30.68±4.21)μg/L,(32.17±3.72)μg/L vs.(38.24±5.86 )μg/L,(39.58±4.28)μg/L,(40.97±4.24)μg/L,(38.92±4.35)μg/L;chemokine CXCL12 [(21.38±3.18)ng /ml, (21.03 ±2.45)ng/ml,(20.78±2.42) ng/ml,(21.54±2.67)ng/ml vs.(28.26±3.37)ng/ml,(27.18±2.94)ng/ml,(27.51±2.89)ng/ml,(27.23±3.15)ng/ml]significantly rose (P <0.01 all)in large size infarction group,NIHSS score > 15 scores group,GCS score>8 scores group and poor prognosis group.Conclusion:Serum levels of A-FABP and chemokine CXCL12 are closely related to occurrence and severity of AIS,which can be used as important indexes for early diagnosis,disease monitor and prognosis assessment in AIS patients.
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Objective:To explore relationship among serum levels of adipocyte fatty acid binding protein (A-FABP), chemokine CXCL12 and acute ischemic stroke (AIS).Methods:A total of 92 aged AIS patients treated in our hospi-tal were selected as AIS group,another 83 healthy subjects undergoing physical examination in our hospital were en-rolled as healthy control group.Serum levels of A-FABP and chemokine CXCL12 were measured and compared be-tween two groups;United states national institutes of health stroke score (NIHSS)was used to assess neurological function deficit degree;Glasgow coma scale (GCS)was used to judge their consciousness.AIS patients were fol-lowed up for three months,then modified Rankin rating score (mRS)was used to assess their prognosis.Results:Compared with healthy control group,there were significant rise in serum levels of A-FABP [(20.92±2.63)μg/L vs.(35.63±5.72)μg/L]and chemokine CXCL12 [(4.25 ±0.61 )ng/ml vs.(24.31 ±3.46)ng/ml]in AIS group,P =0.001 both.Compared with small-medium size infraction group,NIHSS score≤15 scores group,GCS score≤8 scores group and good prognosis group,the levels of FABP [(32.89±5.34)μg/L,(31.72±4.15)μg/L, (30.68±4.21)μg/L,(32.17±3.72)μg/L vs.(38.24±5.86 )μg/L,(39.58±4.28)μg/L,(40.97±4.24)μg/L,(38.92±4.35)μg/L;chemokine CXCL12 [(21.38±3.18)ng /ml, (21.03 ±2.45)ng/ml,(20.78±2.42) ng/ml,(21.54±2.67)ng/ml vs.(28.26±3.37)ng/ml,(27.18±2.94)ng/ml,(27.51±2.89)ng/ml,(27.23±3.15)ng/ml]significantly rose (P <0.01 all)in large size infarction group,NIHSS score > 15 scores group,GCS score>8 scores group and poor prognosis group.Conclusion:Serum levels of A-FABP and chemokine CXCL12 are closely related to occurrence and severity of AIS,which can be used as important indexes for early diagnosis,disease monitor and prognosis assessment in AIS patients.
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BACKGROUND:Stromal cel derived factor-1 is a smal molecular protein with a wide range of biological activity that can cause immune cel chemotaxis, and it also has a chemotactic effect on bone marrow stem cels and periodontal ligament cels. OBJECTIVE:To investigate the effect of stromal cel derived factor-1 with different concentrations on the proliferation of bone marrow stem cels and to probe the best concentration. METHODS:Bone marrow stem cels from beagle dogs were culturedin vitro and stimulated by different concentrations of stromal cel derived factor-1 (100, 200, 300 μg/L). MTT was used to detect the influence of stromal cel derived factor-1 on the proliferation of bone marrow stem cels so as to screen the best concentration of stromal cel derived factor-1. Then, stromal cel derived factor-1 at the best concentrations was used to intervene the bone marrow stem cels, and MTT was used again to detect the proliferation of bone marrow stem cels. RESULTS AND CONCLUSION:Stromal cel derived factor-1 at concentrations of 100, 200, 300 μg/L could promote the proliferation of bone marrow stem cels, and the effect was more notable at 200 and 300 μg/Lbut withno significant difference. Therefore, 200 μg/L was considered to be the best concentration of stromal cel derived factor-1 for intervention of bone marrow stem cels. Compared with the blank control group, 200 μg/L stromal cel derived factor-1 could significantly promote the proliferation of bone marrow stem cels. Taken together, stromal cel derived factor-1 can promote the proliferation of bone marrow stem cels, and its best concentration is 200 μg/L.
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Mesenchymal stem cells (MSCs), for their potential of differentiation into cardiomyocytes and easy acquisition, have been used in repair of myocardium tissue and improvement of heart functions after myocardial infarction. However, a vexed problem is the low homing rate of MSCs no matter what delivery methods (including intravenous, intracoronary or endocardial delivery) are used. SDF-1/CXCR-4 signal pathway plays an important role in variety of stem cell homing, and has been employed to enhance the function of SDF-1/CXCR-4 signal pathway for improving the efficiency of stem cell homing. The present paper has reviewed the methods used recent years to enhance the function of SDF-1/CXCR-4 signal pathway and the mechanism of the signal pathway in MSCs homing.
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Objective To investigate the change of serum concentrations of IL‐17A and CXCL12 in patients with chronic ob‐structive pulmonary disease(COPD) and its correlation with illness severity and formation of lymph follicles .Methods Totally 88 cases of patients with COPD in acute phase in our hospital from 1 January 2014 to 1 January 2015 were selected as the research sub‐jects ,and were divided into mild group(n= 23) ,moderate group(n= 42) and severe group(n= 23) according to the severity of COPD ,and were divided into lymph follicles group(n=21) and non lymph follicles group(n=67) according to lymphoid follicles formation .Enzyme‐linked immunosorbent method was applied to detect the serum IL‐17A and CXCL12 concentrations of these groups in acute aggravating period and stability period ,and parameters of pulmonary function in the same period were also detected . The correlations of serum concentrations of IL‐17A and CXCL12 with illness severity ,formation of lymph follicles and lung function in patients with COPD were analysed .Results Compared with mild group ,serum concentrations of IL‐17A and CXCL12 of moder‐ate group and severe group in acute aggravating period and stable period were increased ,while FEV1 and FVC of medium group and severe group in the same period were decreased;compared with the moderate group ,serum concentrations of IL‐17A and CXCL12 of severe group in acute aggravating period and stable period were increased ,while FEV1 and FVC of severe group in the same period were decreased (P<0 .05) .Compared with non lymph follicles group ,serum concentrations of IL‐17A and CXCL12 of lymph folli‐cles group in acute aggravating period and stable period were increased ,while FEV1 and FVC of lymph follicles group in the same period were decreased (P<0 .05) .The results of correlation analysis showed that serum concentrations of IL‐17A and CXCL12 in patients with COPD were positively correlated to the illness severity and lymph follicle formation rate(IL‐17A :r=0 .728 ,0 .762 ;CXCL12 :r=0 .752 ,0 .776 ,P<0 .05) ,while were negatively correlated to FEV1 and FVC(IL‐17A :r= -0 .756 ,-0 .783 ;CXCL12 :r= -0 .743 ,-0 .767 ,P<0 .05) .Conclusion Serum concentrations of IL‐17A and CXCL12 in patients with COPD were associated with its illness severity ,pulmonary function and lymphoid follicles formation ,which may serve as a reference indexes for the assess‐ment of the illness severity ,pulmonary function and lymph follicle formation .
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Objective To investigate the relationship between the content of stromal cell-derived factor-1 (SDF-1) in myocardium in different period of myocardial infarction and left ventricular function.Methods Twenty three Chinese miniature pigs were randomly divided into the experimental group and the control group.The swines in experimental group were prepared as acute myocardial infarction model by ligating anterior descending coronary artery and were randomly divided into 6 subgroups according to the different time points after infarction.The left ventricular end-diastolic diameter (LVDd),left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were measured respectively.Global circumferential strain (GCS) and global radial strain (GRS) of left ventricle were measured.The content of SDF-1 were also measured by real-time quantitative PCR.Results Compared with the control group,SDF-1 levels were significantly elevated,and LVEF,LVFS,GCS and GRS were reduced.However,LVDd were significantly increased.The content of SDF-1 and GCS has a negative correlation (r =-0.580,P =0.000).Conclusions The content of SDF-1 in myocardial tissue have a certain relationship with GCS of left ventricular myocardium.
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Objective:To construct and evaluate a novel tissue-engineered bone composed of murine stromal cell-derived factor 1(mSDF-1), simvastatin (SIM) and collagen scaffold (Bio-Oss?), serving as a cell-homing approach for bone formation .Methods: In the study , 32 ICR mice were randomly divided into 4 groups,each group including 8 mice.The drug-loaded collagen scaffolds were implanted subcutaneously onto the cranium of each mouse according to the groups: ( 1 ) 1 ∶50 ( volume ratio ) dimethyl sulfoxide ( DMSO ) /phosphate-buffered saline ( PBS ) solution +collagen scaffold ( blank control group ); ( 2 ) 10 -3 mol/L SIM solution +collagen scaffold ( SIM group ); ( 3 ) 200 mg/L mSDF-1solution +collagen scaffold (mSDF-1 group); and (4) 10 -3mol/L SIM +200 mg/L mSDF-1 solution +collagen scaffold ( SIM +mSDF-1 group) .One week after implantation , the mice were trea-ted by injecting the same drug solution mentioned above around the scaffold once a day for two days .The specimens were harvested 6 weeks after implantation and the bone formation was evaluated by soft X-ray analysis , HE staining and immunohistochemical staining .Angiogenesis of each group was checked by calculation of vessels in each tissue section .Results:Six weeks after implantation , the collagen scaffolds were retrieved.The value of gray scale for the SIM +mSDF-1 group[(421 836.5 ±65 425.7) pixels] was significantly higher than that of the blank control group [(153 345.6 ±45 222.2)pixels, P<0.01], the SIM group [(158 119.2 ±100 284.2) pixels, P<0.01], and the mSDF-1 group[(255 529.5 ± 152 142.4) pixels, P <0.05 ]; HE staining analysis revealed that significant bone formation was achieved in the SIM +mSDF-1 group; The immunohistochemical staining showed the existence of os-teopontin and osteocalcin in the SIM +mSDF-1 group; There were more vessels in the SIM +mSDF-1 group[(46 ±8)vessels/mm2] than in the blank control group [(23 ±7) vessels/mm2, P<0.01], and the SIM group[(24 ±6) vessels/mm2 , P<0.01].Conclusion:The novel tissue-engineered bone com-posed of mSDF-1, SIM and collagen scaffolds has the potential to form bone subcutaneously in vivo.It re-presents a novel method of in vivo bone re-generation without seed cell delivery .
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BACKGROUND:Stromal cel-derived factor-1 has a strong chemotaxis to bone marrow mesenchymal stem cels, and both of them can promote wound healing. However, there are less studies on their correlation with skin wound healing. OBJECTIVE:To investigate the effects of stromal cel-derived factor-1 on bone marrow mesenchymal stem cels migration and skin wound repair. METHODS: Thirty SD rats were divided into five groups at random. Bone marrow mesenchymal stem cels labeled with PKH-26 were injected into the rat caudal vein. After 1 week, skin wound models were established. Then, different concentrations (1, 2, 10, 50 μg/L) of stromal cel-derived factor-1 were injected via multi-points on the skin wound. The skin wound healing was observed and recorded at 14 days after injection. The number and distribution of bone marrow mesenchymal stem cels were observed by the fluorescent staining at different time points. The pathological changes of wound tissue were observed by hematoxylin-eosin staining. The expression of colagen I and colagen III were detected by western blot assay. RESULTS AND CONCLUSION:Stromal cel-derived factor-1 at 10 μg/L could induce the largest number of bone marrow mesenchymal stem cels to the skin wound and achieve the best repair results. Stromal cel-derived factor-1 could also regulate the expression of colagen I and colagen III in the wound, and when the concentration of stromal cel-derived factor-1 was 10 μg/L, the expressions of colagen I and colagen II reached the peak. These findings indicate that the appropriate concentration of stromal cel-derived factor-1 is better to promote the migration of bone marrow mesenchymal stem cels, thereby contributing to skin wound repair.
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Objective To observe the translations of chemokine CXCL12 and its receptor CXCR4 in endometrial carcinoma tissues,and to evaluate their significance in clinical pathologic features of endometrial carcinoma.Methods From Jan.2012 to Dec.2014,52 tissue specimens of patients with endometrial carcinoma were admitted to the hospital,aged 55.6 ± 19.2 years,and 26 cases of normal endometrium as control,aged 52.3±16.5 years old.Expressions of CXCL12 and CXCR4 in the tissue specimens were detected by immunohistochemistry,and to analyze the relationship between the expressions and clini-cal pathological features,and FIGO stage,cell differentiation,lymph node metastasis and pathological type in endometrial carcinoma.Results In endometrial carcinoma,the positivity rates of CXCR4 and CXCL12 were 76.92% and 69.23% re-spectively.The positive expression rates of which were 34.62% and 30.77% in normal endometrium tissues,statistically significant (χ2 =11.826,P 0.05).Conclusion The results showed that the expression of CXCL12 and CXCR4 in endometrial carcinoma tissues was significantly increased,which may play an important role in the development of endometrial cancer.
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Objective To explore the relationship between the expression of chemokines and their receptors in the maternal-fetal interface and the pathogenesis of unexplained recurrent spontaneous abortion (URSA). Methods 8-10 weeks CBA/J female mice were mated with DBA/2 and BALB/c male mice at the ratio of 2∶1 to establish the model of normal pregnant mice (CBA/J × BALB/c) and URSA mice (CBA/J × DBA/2). Sixty mice were divided into 6 groups, with ten in each group. The mice in the normal unpregnancy group were executed for endometrial tissues; the mice in the embryonic implantation normal pregnancy group were executed for endometrial tissues at the sixth day of gestation; the mice in the embryonic development normal pregnancy group were executed for decidua and chorionic tissues at the fourteenth day of gestation. While, the mice in the embryonic implantation URSA group were executed for endometrial tissues at the sixth day of gestation;the mice in the pre-abortion URSA group were executed for decidua and chorionic tissues at the ninth day of gestation;the mice in the post-abortion URSA group were executed for decidua and chorionic tissues at the fourteenth day of gestation. The chemokines and their receptors in different tissues of the mice were determined by western blot, including the protein expression of stromal cell derived factor (CXCL12), monocyte chemotactic protein 1 (CCL2), regulated upon activation normal T cell expressed and secreted(RANTES) and their receptor CXCR4, CCR2, CCR5 in maternal-fetal interface. Results (1) The protein expression of CXCL12 and CXCR4, CCL2 and CCR2, RANTES and CCR5 in endometrial tissues of the normal unpregnant group were 0.13±0.04 and 0.18±0.09, 0.057±0.023 and 0.39± 0.08, 0.034 ± 0.012 and 0.22 ± 0.05, respectively. They were 0.35 ± 0.09 and 0.93 ± 0.15, 0.349 ± 0.056 and 0.91 ± 0.15, 0.336 ± 0.089 and 0.44 ± 0.05 in endometrial tissues in the embryonic implantation normal pregnancy group;and were 0.62±0.15 and 1.23±0.28, 0.283±0.051 and 0.55±0.09, 0.225±0.065 and 0.35± 0.07 in decidua tissues in the embryonic development normal pregnancy group. The protein expression of chemokines and their receptors in endometrial tissues in the embryonic implantation normal pregnancy group and in decidua tissues in the embryonic development normal pregnancy group were higher than those in the normal unpregnancy group, with statistically significant difference(P<0.05). Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 in decidual tissues in the embryonic development normal pregnancy group were significantly higher(P<0.05), while CCL2 and CCR2, RANTES and CCR5 were significantly lower (P<0.05). (2) Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 (0.20±0.06 and 0.44±0.11) in endometrial tissues in the embryonic implantation URSA group were significantly lower (P<0.01), while CCL2 and CCR2(0.451±0.133 and 1.32± 0.20), RANTES and CCR5(0.488 ± 0.137 and 0.61 ± 0.18)were higher (P<0.05). (3) Compared with the embryonic development normal pregnancy group, CXCL12 and CXCR4 in decidual tissues of pre-abortion URSA group(0.27 ± 0.09 and 0.26 ± 0.10) , post-abortion URSA group (0.25 ± 0.08 and 0.23 ± 0.08) were significantly lower (P<0.01), while CCL2 and CCR2 (0.576±0.123 and 0.92±0.15 in the pre-abortion URSA group;0.748±0.112 and 1.56±0.34 in the post-abortion URSA group), RANTES and CCR5(0.294±0.054 and 0.59 ± 0.18 in the pre-abortion URSA group;0.363 ± 0.058 and 0.78 ± 0.14 in the post-abortion URSA group) were significantly higher(P<0.05). CCL2 and CCR2, RANTES and CCR5 in decidual tissues in the post-abortion URSA group was obviously higher than those of the pre-abortion URSA group, with statistically significant difference (P<0.05). Couclusions The accurate expression of CXCL12, CCL2, RANTES and their receptors CXCR4, CCR2, CCR5 play important roles in the embryonic implantation and development. The lower expression of CXCL12 and CXCR4 protein and higher expression of CCL2 and CCR2, RANTES and CCR5 in decidua and chorionic tissues are closely related to the pathogenesis of URSA.
ABSTRACT
Introdução: A disfunção endotelial é importante na patogênese da doença cardiovascular (DCV) relacionada à doença renal crônica (DRC). Stromal cell-derived factor-1 (SDF-1) é uma quimiocina que mobiliza células endoteliais progenitoras (EPC) e em conjunto com a interleucina-8 (IL-8) podem ser usadas como marcadores de reparo e lesão tecidual. Objetivo: Neste trabalho, foi investigado o efeito do meio urêmico na expressão de SDF-1 e IL-8 in vivo e in vitro. Métodos: A inflamação sistêmica foi avaliada por meio da proteína C-reativa (PCR) e interleucina-6 (IL-6). IL-8 e SDF-1 foram avaliados por ELISA como marcadores de disfunção endotelial e reparo tecidual, respectivamente. Os estudos in vitro foram realizados em células endoteliais umbilicais humanas (HUVEC) expostas ao meio urêmico ou saudável. Resultados: Foram incluídos nesse estudo 26 pacientes em hemodiálise (HD) (17 ± 3 meses em diálise, 52 ± 2 anos, 38% homens e 11% diabéticos). As concentrações séricas de PCR, IL-6, SDF-1 e IL-8 foram 4,9 ± 4,8 mg/ml, 6,7 ± 8,1 pg/ml, 2625,9 ± 1288,6 pg/ml e 128,2 ± 206,2 pg/ml, respectivamente. Houve correlação positiva entre PCR e IL-6 (ρ = 0,57; p < 0,005) e entre SDF-1 e IL-8 (ρ = 0,45; p < 0,05). Os resultados in vitro demonstraram que a expressão de SDF-1 pelas HUVEC após 6 horas de tratamento com meio urêmico é menor comparada ao tratamento com meio saudável (p < 0,05). Após 12 horas de tratamento, ocorreu aumento de IL-8 quando as HUVECs foram expostas ao meio urêmico (p < 0,005). Conclusão: Sugerimos que SDF-1 e IL-8 nos pacientes em HD podem ser usados para mensurar a extensão do dano e consequente ativação vascular na uremia. .
Introduction: Endothelial dysfunction is important in the pathogenesis of cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as markers of tissue injury and repair. Objective: This study investigated in vivo and in vitro the effect of uremic media on SDF-1 and IL-8 expression. Methods: Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6 (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and tissue repair, respectively, by ELISA. In vitro studies were performed on human umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media. Results: The study included 26 hemodialysis (HD) patients (17 ± 3 months on dialysis, 52 ± 2 years, 38% men and 11% diabetic). Serum concentrations of CRP, IL-6, SDF-1 and IL-8 were 4.9 ± 4.8 mg/ml, 6.7 ± 8.1 pg/ml, 2625.9 ± 1288.6 pg/ml and 128.2 ± 206.2 pg/ml, respectively. There was a positive correlation between CRP and IL-6 (ρ = 0.57, p < 0.005) and between SDF-1 and IL-8 (ρ = 0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1 expression by HUVEC treated with uremic media is lower compared to cells treated with healthy media (p < 0.05). After 12 hours of treatment there was an increase in IL-8 when HUVECs were exposed to uremic media (p < 0.005). Conclusion: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia. .