Objective To evaluate the effects of inflammatory cytokines, including tumor necrosis factorTNF-alpha; and interleukins (IL-6 and IL-8), to the expression of pigment epithelium-derived factor (PEDF) in human retinal pigment epithelium (RPE)cells. Method Cultured primary human RPE cells were treated with 20，2，0.2 , and 0.02 ng/ml of TNF-alpha;, IL-6 and IL-8 separately. The levels of PEDF expression were determined by Western blot of the supernant after 6，12，24 and 48 hours of culture. Results PEDF secretion of RPE cells was inhibited by TNF-alpha;, IL-6 and IL-8 in a time- and dose-dependent fashion. Compared with the controls, the expression of PEDF decreased significantly in 0.02 ng/ml and 6 hours group (F＝7.14, P＜0.05）, 2.00 ng/ml and 48 hours group（F=14.05，P＜0.01) , and 20.00 ng/ml and 24 hours group（F=11.53，P＜0.01). TNF-alpha; was the most strength inhibitor (F＝14,P＜0.01）.Conclusion TNF-alpha;, IL-6, and IL-8 could suppress the expression of PEDF in the cultured human RPE cells.
ObjectiveTo systematically review the relationship between the expression of CXCL12/CXCR4 and pancreatic cancer.MethodsPubMed, EMbase, The Cochrane Library, Wiley Online Library, CNKI, VIP, WanFang Data and CBM databases were electronically searched to collect case-control studies on CXCL12/CXCR4 expression in pancreatic cancer from inception to February 1st 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 21 case-control studies involving 1 677 cases and 1 690 controls were included. The results of meta-analysis showed that the expression of CXCR4 in pancreatic cancer tissue was higher than normal tissue (OR=21.40, 95%CI 5.70 to 80.31, P<0.01), in carcinoma of head of pancreas been higher than carcinoma of pancreatic body and tail, (OR=1.58, 95%CI 1.02 to 2.44, P=0.04), in pancreatic cancer with lymph node metastasis been higher than without lymph node metastasis (OR=3.14, 95%CI 1.98 to 4.99, P<0.01), in pancreatic cancer with high TNM stages (Ⅲ, Ⅳ) been higher than low TNM stages (Ⅰ, Ⅱ) (OR=3.67, 95%CI 1.98 to 6.81, P<0.01), in pancreatic cancer with distant metastasis been higher than without distant metastasis (OR=3.56, 95%CI 1.71 to 7.39, P<0.01), and in pancreatic cancer with vascular invasion was higher than without vascular invasion (OR=3.22, 95%CI 1.70 to 6.09, P<0.01). The expression of CXCR4 was not statistically correlated with age, gender, pancreatic cancer tissue and paracancerous tissue, pancreatic cancer tissue and paracancerous lymph nodes, differentiation degree. There was no statistical correlation between the expression of CXCL12 and the differentiation degree, and lymph node metastasis.ConclusionsIn pancreatic cancer, the high expression of CXCR4 is related to lymph node metastasis, high TNM stage, distant metastasis, vascular invasion indicate poor prognosis. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
ObjectiveTo investigate the expressions and significance of chemokines factor receptors 4 (CXCR4) and chemokines factor receptors 7 (CXCR7) in gastric cancer tissues. MethodsSixty-five patients with gastric cancer who treated in our hospital from January 2011 to June 2013 were retrospectively collected as gastric cancer group, and 20 patients with gastric ulcer were retrospectively collected as control group at the same time. The expressions of CXCR4 and CXCR7 in gastric cancer tissues and normal gastric tissues were measured by immunohistochemistry, and then the relation-ship among expressions of CXCR4/CXCR7 in gastric cancer tissues and clinicopathological features of patients with gastric cancer was explored, as well as its effect on survival. ResultsPositive expression rates of CXCR4 and CXCR7 were identi-fied in 80.00% (52/65) and 84.62% (55/65) of the gastric cancer group, and 5.00% (1/20) and 10.00% (2/20) in control group respectively, and the positive expression rates of CXCR4 and CXCR7 in gastric cancer group were significantly higher than those of control group respectively (χ2=36.65, P<0.01; χ2=38.55, P<0.01). The positive expression rate of CXCR4 in gastric cancer tissues was related with degree of differentiation, T staging, and TNM staging (P<0.05), positive expression rate of CXCR4 in patients with poor differentiation, T3-4 staging, and TNM Ⅲ-Ⅳ staging were higher than corresponding patients with moderate/high degree of differentiation, T1-2 staging, and TNM Ⅰ-Ⅱ staging. The positive expression rate of CXCR7 in gastric cancer tissues was related with degree of differentiation, T staging, and N staging (P<0.05), positive expression rate of CXCR7 in patients with poor differentiation, T3-4 staging, and N1-3 staging were higher than corrsponding patients with moderate/high degree of differentiation, T1-2 staging, and N0 staging. The survival situation was worse in patients with positive expression of CXCR4 and CXCR7 than corresponding patients with negative expression (P=0.01, P=0.01) respectively. ConclusionsCXCR4 and CXCR7 are related to gastric cancer genesis and development. Furthermore, the expressions of CXCR4 and CXCR7 could be used as markers to predict prognosis of gastric cancer. The regulation of CXCR4/chemokine ligand 12 (CXCL12) axis and CXCR7/CXCL12 axis may provide a new targeted therapy for patients with gastric cancer.
Objective To investigate the expression of chemokine receptor CXCR7 and the relation between its expression and clinicopathologic characteristics in papillary thyroid carcinoma. Method The expressions of CXCR7 in 79 cases of papillary thyroid carcinoma and their paracancerous tissues，and 33 cases of benign thyroid lesion tissues were detected by immunohistochemistry. Results The positive expression rates of CXCR7 were 0（0/79），65.8%（52/79），and 30.3%（10/33） in the paracancerous tissues，papillary thyroid carcinoma tissues，and benign thyroid lesions tissues，respectively. The positive expression rate of CXCR7 in the papillary thyroid carcinoma tissues was significantly higher than that in the paracancerous tissues （P＜0.05） or benign thyroid lesion tissues（P＜0.05）. The expression of CXCR7 was correlated with lymph node metastasis （P＜0.05）. Conclusion CXCR7 might take part in tumorigenesis，progression，and lymph node metastasis of papillary thyroid carcinoma.
Objective To observe the levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in aqueous humor of patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods Forty eyes of 40 consecutive patients with macular edema secondary to CRVO (CRVO group) were enrolled in this study. The patients included 25 males and 15 females. The patient age ranged from 38 to 76 years. The control group was 20 patients with senile cataract who underwent phacoemulsification, including 10 males and 10 females. The levels of VEGF165, VEGF165b, IL-6 and MCP-1 in aqueous humor were determined by enzymelinked immunosorbent assay. The correlation of VEGF, and IL-6, and MCP-1 were analyzed. Results The median aqueous level of VEGF165, IL-6 and MCP-1 were 1089.0, 165.6, 1253.0 pg/ml respectively in CRVO group, which were higher than the control group's results (168.2, 4.7, 216.4 pg/ml respectively), the differences were statistically significant (Z=-4.549, -6.008, -5.343;P＜0.001). The VEGF165b in CRVO group and control group were 834.0, 915.9 pg/ml respectively, the difference was not statistically significant (Z=-0.207，P＞0.05). The ratio of VEGF165b to VEGF165 in CRVO group and control group were 2.71, 7.28 respectively, the difference was statistically significant (t=-3.007，P＜0.05). There was a highly positive correlation between IL-6 and VEGF in CRVO group (r=0.526,P=0.001) and also mild positive correlation in control group (r=0.425，P=0.070). No correlation between MCP-1 and VEGF was observed in both groups (CRVO group: r=0.211,P＞0.05. Control group: r=-0.019,P＞0.05). Conclusions VEGF165, IL-6 and MCP-1 levels were increased in CRVO patients while the VEGF165b was normal. The ratio between VEGF165b and VEGF165 in aqueous humor of patients with macular edema secondary to CRVO was decreased.
ObjectiveTo detect expressions of interleukin-17 (IL-17) and interleukin-27 (IL-27) proteins in liver tissue of hepatic alveolar echinococcosis. MethodsThe edge liver tissues (from the lesion edge 0.5 cm) and the normal liver tissues (from the lesion edge 5 cm) of 20 patients with hepatic alveolar echinococcosis in the Affiliated Hospital of Qinghai University were collected and stored at-80℃ freezer. The immunohistochemical method was used to detect the expressions of IL-17 and IL-27 proteins in these two tissues. ResultThe positive rates of IL-17 and IL-27 protein expressions in the edge liver tissues were significantly higher than those in the normal liver tissues[IL-17:80.0% (16/20) versus 10.0% (2/20), χ2=12.36, P < 0.01; IL-27:85.0% (17/20) versus 20.0% (4/20), χ2=12.36, P < 0.01]. ConclusionHigh expressions of IL-17 and IL-27 protein in edge liver tissue might participate in progress of hepatic alveolar echinococcosis.
ObjectiveTo review the recent research progress of the regulatory mechanisms of osteoclast (OC) formation and functions. MethodsThe related literature on OC formation, activation, and functions was reviewed, analyzed, and summarized. ResultsMacrophage colony stimulating factor and receptor activator of nuclear factor-κB ligand are essential cytokines which regulate all aspects of OC formation and functions. In additional to mediating bone resorption, OCs also partici pate in regulation of osteoblast formation and immune responses. ConclusionThe researches on the regulation of OC formation and functions have further revealed the destruction mechanisms of various kinds of bone diseases, which will facil itate to find more suitable biological targets for cl inical therapy.
Mesenchymal stem cells (MSC) are considered to have important value in the treatment of various diseases because of their low immunogenicity, transferability, and strong tissue repair capacity. Stromal cell derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) pathway plays an important role in migration of MSC. The induction of homing of MSC to retina by regulating SDF-1/CXCR4 may exert the curative effect on diabetic retinopathy to greatest exent.
Objective The observe the effects of interferon-inducible protein-10 (IP-10) on proliferation, migration and capillary tube formation of human retinal vascular endothelial cells (HREC) and human umbilical vein endothelial cells (HUVEC). Methods The chemokine receptor (CXCR3) mRNA of HREC and HUVEC were quantified by reverse transcriptase polymerase chain reaction (RT-PCR). In the presence of the different concentrations of IP-10, the difference in proliferation capacity of HREC and HUVEC were analyzed by cell counting kit-8 (CCK-8) methods. Wound scratch assay and threedimensional in vitro matrigel assay were used for measuring migration and capillary tube formation of HREC and HUVEC, respectively. Results RT-PCR revealed both HREC and HUVEC expressed CXCR3. The proliferation of HREC in the presence of IP-10 was inhibited in a dosagedependent manner (F=6.202,P＜0.05), while IP-10 showed no effect on the inhibitory rate of proliferation of HUVEC (F=1.183,P＞0.05). Wound scratch assay showed a significant reduction in the migrated distance of HREC and HUVEC under 10 ng/ml or 100 ng/ml IP-10 stimulation (F=25.373, 23.858; P＜0.05). There was no effect on the number of intact tubules formed by HREC in the presence of 10 ng/ml or 100 ng/ml IP-10. The number of intact tubules formed by HREC in the presence of 1000 ng/ml IP-10 was remarkably smaller. The difference of number of intact tubules formed by HREC among 10, 100, 1000 ng/ml IP-10 and nonintervention group was statistically significant (F=5.359,P＜0.05). Conclusion IP-10 can inhibit the proliferation, migration and capillary tube formation ability of HREC and the migration of HUVEC.
Objective To investigate the influence on matrix metalloproteinases (MMP) 3, 9, and 13 levels of human articular cartilage cells after blocking stromal cell derived factor 1 (SDF-1)/ chemokine receptor 4 (CXCR4) signaling pathway withAMD3100 and to define the function mechanism of AMD3100. Methods A total of 144 cartilage blocks from 12 osteoarthritis (OA) patients undergoing total knee arthroplasty (OA cartilage group) and 144 normal cartilage blocks (Mankin score of 0 or 1) from 12 patients undergoing traumatic amputation (normal cartilage group). OA cartilage group was further divided into subgroups A1, B1, and C1, and normal cartilage group into subgroups A2, B2, and C2. The cartilage tissues were cultured in DMEM solution containing 100 ng/mL SDF-1 and 1 000 nmol/L AMD3100 in subgroup A, 100 ng/mL SDF-1 and 1 000 nmol/L MAB310 in subgroup B, and 100 ng/mL SDF-1 in subgroup C, respectively. The levels of MMP-3, 9, and 13 were measured by ELISA; the expressions of MMP-3, 9, and 13mRNA were tested by RT-PCR. Results ELISA and RT-PCR results showed that the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly lower in subgroup A than in subgroups B and C at the same time points (P lt; 0.05); the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly higher in OA cartilage group than in normal cartilage group at the same time points (P lt; 0.05). Conclusion SDF-1 could induce overexpression and release of MMP-3, 9, and 13 in the articular cartilage through the SDF-1/CXCR4 signaling pathway; AMD3100 could reduce the mRNA expressions and secretion of MMP-3, 9, and 13 in OA cartilage by blocking the SDF-1/CXCR4 signaling pathway; but AMD3100 could not make the secretion of MMP-3, 9, and 13 return to normal levels in OA cartilage.