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 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.
Circadian rhythm is a physiological regulation mechanism evolved by the body to adapt to the 24-hour fluctuations in the internal and external environment. It plays an important role in many physiological and pathological processes including the immune system. Neutrophils are the most important immune cells in the human circulation, and their numbers and phenotypes also show obvious circadian fluctuations. A growing number of studies have shown that the cellular and molecular mechanisms of neutrophil circadian rhythms are disease-related. Combining the latest research on neutrophil circadian rhythm, this article briefly introduces the recruitment of neutrophils in the bone marrow, the aging of neutrophils and their infiltration into various tissues of the body, and discusses the interventions. It also discusses the therapeutic prospects based on neutrophil circadian rhythm-related mechanisms from the perspectives of intervening neutrophil aging-related chemokines and chronotherapy.
ObjectiveTo review the role of chemokine networks in regulating synovial macrophage heterogeneity during osteoarthritis (OA) pathogenesis. Methods A review of recent literature on the developmental origins of OA synovial macrophages, single-cell transcriptomic characteristics, and chemokine signaling pathways was conducted to systematically summarize the functional phenotypes, immunometabolic mechanisms, and regulatory roles of synovial macrophages in OA. Results OA has been established as a low-grade, chronic inflammatory disease affecting the entire joint. Single-cell and spatial transcriptomic studies have confirmed that synovial macrophages are not a single population but rather a dynamic continuum of different functional states, including steady-state barrier-like, inflammatory amplification, fibrosis-related, and lipid-enriched phenotypes. Chemokine networks play a dual crucial role in this process: on one hand, chemokine gradients guide the migration of peripheral monocytes to the synovium and influence their differentiation; on the other hand, synovial macrophages in different states secrete chemokines, mediating transcellular communication between the synovium, subchondral bone, and peripheral nerves. This process reshapes the microenvironment and amplifies local inflammation and pain signals. Current therapeutic strategies targeting macrophage metabolic reprogramming and chemokine axis blockade show potential clinical applications. Conclusion Re-examining the interaction between synovial macrophages and microenvironment and constructing an integrated perspective of “lineage-state-chemokine network” will help to understand the pathological progression mechanism of OA. In the future, it is expected to provide a theoretical framework and intervention targets for the precise immune regulation of OA and the development of new targeted drugs by accurately analyzing the spatiotemporal evolution of macrophage subsets and their interaction with chemokines.
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.
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 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 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.
Objective To investigate the expression and clinical significance of CXCR4 in esophageal squamous cell carcinoma (ESCC). Methods Databases including PubMed, EMbase, Web of Science, CBM, VIP, CNKI and WanFang Data were searched from inception to April 2012, and the relevant references were also retrieved to collect relevant case-control studies. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the quality of the included studies. Then the meta-analysis was conducted using RevMan 5.1 software. Results A total of 5 case-control studies involving 493 ESCC tissues and 136 normal esophageal tissues were included. The results of the meta-analyses showed that, as for the positive rate of CXCR4 expression, it was higher in ESCC tissues rather than normal esophageal tissues (OR=12.03, 95%CI 6.76 to 21.44, Plt;0.000 01), in ESCC tissues with lymph node metastasis rather than those without lymph node metastasis (OR=4.35, 95%CI 2.48 to 7.62, Plt;0.000 01), as well as in moderate and low differentiated ESCC tissues rather than high differentiated ESCC tissues (OR=0.51, 95%CI 0.32 to 0.81, P=0.004); but no significant difference was found between the clinical stage I-II and clinical stage III-IV ESCC tissues. Conclusion The presently limited evidence shows CXCR4 expression is associated with ESCC, lymph node metastasis and degree of cell differentiation, indicating that CXCR4 may take a role in the whole course of carcinogenesis of ESCC. But the relationship between CXCR4 expression and clinical stage of ESCC is still unclear, which needs to be further proved by more large-scale, well-designed and high quality case-control studies.