Objective:Vitiligo is a relatively common skin disfiguring disorder that exhibits a fluctuating course between activity and stability,making monitoring and management challenging.Autoimmunity plays a crucial role in t...Objective:Vitiligo is a relatively common skin disfiguring disorder that exhibits a fluctuating course between activity and stability,making monitoring and management challenging.Autoimmunity plays a crucial role in the pathogenesis of vitiligo.Numerous autoimmune disorders have been associated with both CD27 and chemokine(C-X-C motif)ligand 10(CXCL10).However,trials evaluating their role in vitiligo are lacking in the Egyptian setting.We evaluated the circulating levels of these 2 biomarkers in patients with vitiligo and the possible correlation between their levels and disease activity.Methods:This cross-sectional study included 70 patients with vitiligo and 20 healthy controls.The patients were clinically assessed and then divided into active and stable groups according to clinical signs of activity and Vitiligo Disease Activity scores.The levels of CD27 and CXCL10 in the serum were assessed using an enzyme-linked immunosorbent assay in both the patients and the controls,then the Mann-Whitney U and Kruskal-Wallis tests were used to analyze the difference between the groups.Results:Active and stable vitiligo patients have significantly higher median serum CXCL10(385.9 and 245.2 pg/mL)and CD27(61.6 and 66.5 ng/mL)levels compared to the controls(193 pg/mL and 52.5 ng/mL,respectively,all P<0.05).In vitiligo cases,although CXCL10 levels significantly increased with disease activity(P<0.001),CD27 levels were comparable between the 2 subgroups(P=0.953).CXCL10 positively correlated with disease activity(r=0.887,P<0.001).CXCL10 had a higher sensitivity and a lower specificity(95.7%and 60.0%,respectively)compared to CD27(71.4%and 75%,respectively)for differentiating cases from controls.Conclusion:There is a possibility that CXCL10 and CD27 are involved in the development and course of vitiligo.展开更多
In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1...In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1） have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1（p JNK1） and p JNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective p JNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the p JNK/CXCL1 pathway may provide a new choice for treatment of CIBP.展开更多
Epstein-Barr virus (EBV) infects over 90% of the global population, establishing latent infections in most individuals. Under specific conditions like inflammation and immune suppression, EBV can be reactivated, leadi...Epstein-Barr virus (EBV) infects over 90% of the global population, establishing latent infections in most individuals. Under specific conditions like inflammation and immune suppression, EBV can be reactivated, leading to the initiation and progression of related diseases. While inflammation is known to induce EBV reactivation, the precise mechanisms underlying this phenomenon remain unclear. Chemokine (C-X-C motif) ligand (CXCL10), a key inflammatory factor, plays a significant role in various infectious diseases. In this study, we investigated how CXCL10 levels regulate the transition between the latent and lytic replication phases of the EBV lifecycle using cell culture, Western blot, fluorescent quantitative PCR, immunofluorescence, and flow cytometric apoptosis assays. Our findings indicate that CXCL10 induces EBV transition from latency to lytic replication through its receptor CXCR3 by regulating the downstream effector, exostosis-like glycosyltransferase 1. Additionally, CXCL10 activates the JAK2/STAT3 pathway. This study confirms the role of CXCL10 in promoting EBV lytic replication, providing crucial insights into the pathogenic mechanisms of inflammation-triggered EBV reactivation.展开更多
文摘Objective:Vitiligo is a relatively common skin disfiguring disorder that exhibits a fluctuating course between activity and stability,making monitoring and management challenging.Autoimmunity plays a crucial role in the pathogenesis of vitiligo.Numerous autoimmune disorders have been associated with both CD27 and chemokine(C-X-C motif)ligand 10(CXCL10).However,trials evaluating their role in vitiligo are lacking in the Egyptian setting.We evaluated the circulating levels of these 2 biomarkers in patients with vitiligo and the possible correlation between their levels and disease activity.Methods:This cross-sectional study included 70 patients with vitiligo and 20 healthy controls.The patients were clinically assessed and then divided into active and stable groups according to clinical signs of activity and Vitiligo Disease Activity scores.The levels of CD27 and CXCL10 in the serum were assessed using an enzyme-linked immunosorbent assay in both the patients and the controls,then the Mann-Whitney U and Kruskal-Wallis tests were used to analyze the difference between the groups.Results:Active and stable vitiligo patients have significantly higher median serum CXCL10(385.9 and 245.2 pg/mL)and CD27(61.6 and 66.5 ng/mL)levels compared to the controls(193 pg/mL and 52.5 ng/mL,respectively,all P<0.05).In vitiligo cases,although CXCL10 levels significantly increased with disease activity(P<0.001),CD27 levels were comparable between the 2 subgroups(P=0.953).CXCL10 positively correlated with disease activity(r=0.887,P<0.001).CXCL10 had a higher sensitivity and a lower specificity(95.7%and 60.0%,respectively)compared to CD27(71.4%and 75%,respectively)for differentiating cases from controls.Conclusion:There is a possibility that CXCL10 and CD27 are involved in the development and course of vitiligo.
基金supported by the National Natural Science Foundation of China(No.81172150)
文摘In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1） have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1（p JNK1） and p JNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective p JNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the p JNK/CXCL1 pathway may provide a new choice for treatment of CIBP.
文摘Epstein-Barr virus (EBV) infects over 90% of the global population, establishing latent infections in most individuals. Under specific conditions like inflammation and immune suppression, EBV can be reactivated, leading to the initiation and progression of related diseases. While inflammation is known to induce EBV reactivation, the precise mechanisms underlying this phenomenon remain unclear. Chemokine (C-X-C motif) ligand (CXCL10), a key inflammatory factor, plays a significant role in various infectious diseases. In this study, we investigated how CXCL10 levels regulate the transition between the latent and lytic replication phases of the EBV lifecycle using cell culture, Western blot, fluorescent quantitative PCR, immunofluorescence, and flow cytometric apoptosis assays. Our findings indicate that CXCL10 induces EBV transition from latency to lytic replication through its receptor CXCR3 by regulating the downstream effector, exostosis-like glycosyltransferase 1. Additionally, CXCL10 activates the JAK2/STAT3 pathway. This study confirms the role of CXCL10 in promoting EBV lytic replication, providing crucial insights into the pathogenic mechanisms of inflammation-triggered EBV reactivation.
