CXC chemokine ligand 12 (CXCL12) is a kind of small molecular polypeptide substance that can move cells towards specific parts. It is widely distributed in heart, skeletal muscle, liver, brain and so on. Current studies believe that CXCL12 plays a role in the formation and progression of cardiovascular diseases by binding to CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), but the mechanism is not very clear, and even some contrary experimental results appear. This review mainly discusses the role of CXCL12-CXCR4/ACKR3 axis in atherosclerosis, myocardial infarction, and myocardial remodeling, in order to explore the inflammatory mechanism in the development of coronary heart disease and provide a basis for further research of clinical drugs.
Neurosyphilis is a group of clinical syndromes in which Treponema pallidum invades the nervous system and causes damage to the meninges, blood vessels, brain parenchyma or spinal cord. At present, there is no highly specific and sensitive method for the diagnosis of neurosyphilis, and its diagnosis mainly depends on clinical manifestations, abnormal cerebrospinal fluid and the comprehensive judgment of clinicians. Current studies show that some cytokines and chemokines are promising for laboratory detection of neurosyphilis. This article reviews the research progress of neurosyphilis from the aspects of traditional laboratory testing, polymerase chain reaction testing, cytokine and chemokine testing, and existing diagnostic criteria for neurosyphilis, in order to provide a reference for clinical testing and follow-up research.
Objective To systematically evaluate the value of CXC chemokine ligand 9 (CXCL9) in the diagnosis of tuberculosis. Methods Literature on the diagnosis of tuberculosis by plasma CXCL9 were collected by searching PubMed, EBSCO, China National Knowledge Infrastructure and Wanfang databases form establishment to September 2022, and then literature screening, data extraction and quality assessment were performed independently by two researchers. Meta-analysis was performed using Review Manager 5.3 and Stata 15 softwares. Results According to the inclusion and exclusion criteria, 10 articles were selected, including 1586 participants from 5 countries and regions. Meta-analysis results showed that the positive rate of CXCL9 was higher in active tuberculosis patients than that in healthy people and latent tuberculosis patients [active tuberculosis patients vs. healthy people: odds ratio (OR)=21.69, 95% confidence interval (CI) (6.52, 72.16), P<0.00001; active tuberculosis patients vs. latent tuberculosis patients: OR=10.12, 95%CI (3.83, 26.76), P<0.00001]. The sensitivity and specificity of plasma CXCL9 in distinguishing active tuberculosis patients from healthy people were 0.84 [95%CI (0.77, 0.90)] and 0.82 [95%CI (0.63, 0.92)], respectively; the sensitivity and specificity of plasma CXCL9 in distinguishing active tuberculosis patients from latent tuberculosis patients were 0.77 [95%CI (0.56, 0.90)] and 0.72 [95%CI (0.40, 0.91)], respectively. Subgroup analysis showed that the infection status of human immunodeficiency virus had some impact on heterogeneity, while other factors had limited impact on heterogeneity. Egger test showed that there was no publication bias (active tuberculosis patients vs. healthy people: P=0.976; active tuberculosis patients vs. latent tuberculosis patients: P=0.606). Conclusion CXCL9 has a high diagnostic value for tuberculosis patients and may be used as a new biomarker to diagnose tuberculosis.
Objective To understand role of chemokines and their receptors in pathogenesis, progression, and metastasis of gastric cancer, and to provide a better approach for diagnosis and treatment of gastric cancer. Method The literatures about the relationship between chemokines and their receptors and gastric cancer were reviewed. Results There were about 50 various chemokines and their receptors abnormally expressed in the tumor microenvironment. The main types related gastric cancer were the CXC, CC and CX3C chemokines and their receptors, which could promote the proliferation, invasion, and metastasis of the gastric cancer through several pathways like mTOR pathway, JAK2-STAT3 pathway, etc.. Conclusions Chemokines and their receptors play an important role in occurrence and development of gastric cancer. Further studies on chemokines and their receptors will not only assist in early diagnosis of gastric cancer, as well as estimation of clinical prognosis, but also provide an intervention target for gastric cancer.
Objective To study the expression and significance of CCR chemokine receptor-7 (CCR7) protein and vascular endothelial growth factor-D (VEGF-D) protein in the progression of breast cancer, including normal breast tissue, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods Immunohistochemistry was used to detect the expression of CCR7 and VEGF-D protein in the nomal breast tissue (n=20), slight and moderate ductal atypical hyperplasia tissue (n=20), severe atypical hyperplasia and intraductal carcinoma in situ tissue, as well as invasive ductal breast carcinoma tissue (n=73). In addition, the D2-40 staining was also used to determine lymphatic microvessel density (LMVD). Meanwhile, the relationship between the expression of the two kinds of protein and clinicopathological factors/LMVD was analyzed by statistical analysis in breast cancer, and the correlation between expression of CCR7 protein and expression of VEGF-D protein was analyzed too. Results ①The positive rates of CCR7 protein (χ 2 =23.905，P<0.050) and VEGF-D protein (χ 2 =22.349，P<0.050) were gradually increased in the normal breast tissue group 〔CCR7 protein: 0 (0/20), VEGF-D protein: 5.0% (1/20)〕, slight and moderate atypical hyperplasia group 〔CCR7 protein: 5.0% (1/20), VEGF-D protein: 20.0% (4/20)〕, severe atypical hyperplasia and intraductal carcinoma in situ group 〔CCR7 protein: 30.0% (6/20), VEGF-D protein: 40.0% (8/20)〕, and invasive ductal carcinoma group 〔CCR7 protein: 47.9% (35/73), VEGF-D protein: 57.5% (42/73)〕. ②The LMVD value gradually increased in normal breast tissue group (2.00±1.02), slight and moderate atypical hyperplasia group (6.70± 3.48), severe atypical hyperplasia and intraductal carcinoma in situ group (9.01±2.13), as well as invasive ductal carcinoma group (16.32±4.07), there was significant difference between any 2 groups (P<0.050). ③The expressions of CCR7 protein and VEGF-D protein were correlated with clinical staging, histological grading, lymph node metastasis, and expression of human epidermal growth factor receptor-2 (HER-2) protein in patients with breast cancer (P<0.050), the higher positive rates of CCR7 and VEGF-D protein occurred in patients with higher histological grading, later clinical staging of Ⅲ+Ⅳ (compared with staging of Ⅰ+Ⅱ), lymph node metastasis (compared with no lymph node metastasis), and positive expression of HER-2 protein (compared with negative expression of HER-2 protein). The result indicated that LMVD value was related with expression of VEGF-D protein (r=0.623, P<0.010) in patients with breast cancer, but there was no correlation with expression of CCR7 protein (r=-0.303, P>0.050). Furthermore, there was weak positive correlation between expression of CCR7 protein and expression of VEGF-D protein in breast cancer (r=0.112, P<0.050). Conclusion The results strongly suggest that the expression levels of the VEGF-D protein and CCR7 protein indicate the potential of translation some extent, and they play an important role in the progression of breast cancer.
Objective To investigate the role of chemokine receptor CXCR7 in the development and progression of pancreatic carcinoma. Methods The short hairpin RNA (shRNA) targeting CXCR7 was designed and delivered into AsPC-1 pancreatic carcinoma cells to knock down CXCR7 expression. The cell proliferation, cell cycle, and apoptosis after CXCR7 knockdown was determined by MTT and flow cytometry, respectively. The invasive ability of pancreatic carcinoma cells was evaluated by using the Transwell system. Results Compared with the blank control group (BC group), transfection of AsPC-1 cells with CXCR7-shRNA resulted in a significantly decreased expression of CXCR7 at both mRNA and protein levels (P<0.05), and the ability of proliferation and invasion significantly decreased (P<0.05). Knockdown of CXCR7 also significantly increase apoptosis (P<0.05), induce cell cycle arrest at G0/G1 phase (P<0.05). Conclusions Taken together, the present study showes that the knockdown of CXCR7 expression may play an important role in pancreatic carcinoma development, invasion, and metastasis, CXCR7 may be a potential therapeutic target for the treatment of pancreatic carcinoma.
ObjectiveTo investigate the expressions of stromal cell-derived factor-1 (SDF-1) and chemokine receptor-4 (CXCR4) in local tissues of perianal abscess and their relationships with clinicopathological features and prognosis of patients.MethodsA total of 47 patients with perianal abscess (perianal abscess group) and 58 patients with mixed hemorrhoids (mixed hemorrhoids group) were selected for the study. The tissues were collected during the operation. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expressions of SDF-1 mRNA and CXCR4 mRNA in local tissues of the two groups, the positive expressions of SDF-1 protein and CXCR4 protein in local tissues were detected by immunohistochemistry, and the relationships between the expressions of SDF-1 and CXCR4 protein and the clinical characteristics, prognosis of patients were analyzed.ResultsThe expression levels of SDF-1 mRNA and CXCR4 mRNA in the perianal abscess group were higher than those in the mixed hemorrhoids group, and the positive rates of SDF-1 protein and CXCR4 protein in the perianal abscess group were higher than those in the mixed hemorrhoids group too (P<0.05). The expressions of SDF-1 protein and CXCR4 protein in perianal abscess tissues were both not related to sex, age, location of abscess, and course of disease (P>0.05), but was related to abscess diameter, healing time, and anal fistula (P<0.05). The non-recurrence rates of SDF-1 protein-negative group and CXCR4 protein-negative group were lower than those of SDF-1 protein-positive group and CXCR4 protein-positive group respectively (P<0.05).ConclusionSDF-1 and CXCR4 molecular are up-regulated in the local tissues of perianal abscess, which are related to the size of abscess, healing time, anal fistula, and recurrence of patients.
Objectives To observe the expression of CCL1/CCR8 mRNA in murine lung tissue of bronchial asthma and effects of glucocorticoids on their expression. Methods Thirthy healthy mice were randomly divided into a control group, an asthma group, and a dexamethasone group, with 10 mice in each group. The sensitized murine asthma model was induced by ovalbumin sensitization and challenge, and the dexamethasone group were peritoneally injected with dexamethasone( 2 mg/ kg) . Total and differential cell counts in BALF were measured. IL-4 Level in BALF was evaluated by ELISA. The expression of CCL1 and CCR8 mRNA in the lungs were measured by semi-quantitative RT-PCR. Results The percentage of eosinophils, lymphocyte and IL-4 level in the asthma group increased significantly compared with the controlgroup, and which in the dexamethasone group decreased significantly compared with the asthma group and still higher than the control group( all P lt; 0. 01) . The expression of CCL1 and CCR8 mRNA had the same tendency ( all P lt;0. 01) . Conclusions The gene expression of CCL1/CCR8 is up-regulated in allergic asthma mice.Glucocorticoids can relieve airway inflammation of asthma probably by inhibiting CCL1/CCR8 expression.
Objective To observe the expressions of CXC chemokine receptor 4 (CXCR4) in muscle satell ite cells in situ of normal and cardiotoxin-intoxicated muscle tissues so as to further investigate the molecular mechanism involving inmuscle regeneration such as progressing muscular dystrophy (PMD) for seeking the way to cure muscle retrogression. Methods The muscle injured model of 12 C57 male mice was made by injecting cardiotoxin (5 μg per mouse) in left quadriceps femoris, their right quadriceps femoris was used as control without any injection. The histological, immunohistochemical analysis and RT-PCR were done to investigate the expression of CXCR4 in the quadriceps femoris in situ after 1 day, 4 days, 1 week, 2 weeks, 4 weeks and 6 weeks. Results HE staining results demonstrated that the muscle tissues experienced the process from muscle injury, repair to regeneration. The result of immunohistochemistry showed that the expressions of CXCR4 in injured muscle tissue were 1 955.6 ± 150.3, 2 223.2 ± 264.3, 2 317.6 ± 178.7, 3 066.5 ± 269.6, 1 770.9 ± 98.7 and 1 505.7 ± 107.1 at 1 day, 4 days, 1 week, 2 weeks, 4 weeks and 6 weeks after injection of cardiotoxin, there was significant difference when compared with normal muscle (640.3 ± 124.0, P lt; 0.001). The RT-PCR showed that the expressions of CXCR4 mRNA in injured muscle tissue were0.822 ± 0.013, 0.882 ± 0.025, 1.025 ± 0.028, 1.065 ± 0.041, 0.837 ± 0.011 and 0.777 ± 0.015 at 1 day, 4 days, 1 week, 2 weeks, 4 weeks and 6 weeks after injection of cardiotoxin, there was significant difference when compared with normal muscle (0.349 ± 0.006, P lt; 0.001). Conclusion CXCR4 may be the critical protein in the process of muscle impairment and reparation.
Objective To identify immune-related genes critical to asthma pathogenesis and construct a clinically applicable diagnostic model based on immune-gene signatures. Methods We first intersected 1639 immune-related genes (IRGs) with differentially expressed genes (DEGs) from the discovery dataset (GSE43696, n=128) to obtain differentially expressed IRGs (DE-IRGs). Expression stability was confirmed in the independent validation dataset GSE64913 (n=62). Least absolute shrinkage and selection operator (LASSO) regression and support-vector-machine (SVM) recursive feature elimination were applied to rank genes, followed by overlap with key modules identified by weighted gene co-expression network analysis (WGCNA). A logistic-regression diagnostic model was constructed using the optimal gene set, and its functional landscape was interrogated by gene-set enrichment analysis (GSEA). Finally, the model and the selected genes were cross-validated in ten transcriptomic cohorts encompassing eight distinct asthma phenotypes (total n=1137) and in lung tissue from an ovalbumin (OVA)-induced murine asthma model. Results A total of 38 DE-IRGs were identified. Among them, cholecystokinin (CCK), cellular retinol binding protein 2 (CRABP2) and C-X-C motif chemokine ligand 6 (CXCL6) were involved in immune-related processes and signaling pathways, which were of great significance in the diagnosis of asthma. The logistic regression diagnostic model based on three genes has shown good universality in various asthma samples. These three genes have also been verified to a certain extent in the lung tissues of OVA mice. Conclusion Integrative bioinformatics and in vivo validation establish CCK, CRABP2, and CXCL6 as a compact, biologically grounded immune-gene signature for asthma diagnosis and mechanistic investigation.