Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors pl...Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.展开更多
Chemokines can be divided into four categories: α, β, γ, and δ. Chemokine α is related to neutrophil chemotaxis. Chemokine β is correlated with adsorption of monocytes,basophils, and eosinophils. Chemokine γ is...Chemokines can be divided into four categories: α, β, γ, and δ. Chemokine α is related to neutrophil chemotaxis. Chemokine β is correlated with adsorption of monocytes,basophils, and eosinophils. Chemokine γ is mainly a lymphocyte chemokine. Function of chemokine δ remains unclear. Chemokines α and β are primarily related to occurrence and development of autoimmune thyroid disease. This study reviews chemokines and their receptors that are related to Graves’ disease and Hashimoto’s thyroiditis.展开更多
近日,武汉大学国家网络安全学院2022级硕士生方正撰写的论文被第31届国际计算机与通信安全会议(ACM Conference on Computer and Communications Security,ACM CCS2024)录用。论文题目为“Zero-Query Adversarial Attack on Black-box A...近日,武汉大学国家网络安全学院2022级硕士生方正撰写的论文被第31届国际计算机与通信安全会议(ACM Conference on Computer and Communications Security,ACM CCS2024)录用。论文题目为“Zero-Query Adversarial Attack on Black-box Automatic Speech Recognition Systems”(《针对黑盒智能语音识别系统的零查询对抗攻击》),指导老师为武汉大学国家网络安全学院王骞教授和赵令辰副教授(通讯作者),与清华大学李琦副教授、西安交通大学沈超教授合作完成。国家网络安全学院2022级硕士生王涛、2022级博士生张神轶、2022级硕士生李博文和2021级博士生葛云洁参与了该成果的研究工作。展开更多
近日,西安电子科技大学网络与信息安全学院李兴华教授团队的研究成果“PIC-BI:Practical and Intelligent Combinatorial Batch Identificationfor UAV Assisted Io T Networks”以及李金库教授团队的研究成果“Boosting Practical Cont...近日,西安电子科技大学网络与信息安全学院李兴华教授团队的研究成果“PIC-BI:Practical and Intelligent Combinatorial Batch Identificationfor UAV Assisted Io T Networks”以及李金库教授团队的研究成果“Boosting Practical Control-Flow Integrity with Complete Field Sensitivity and Origin Awareness”同时被ACM CCS2024国际学术会议全文收录,并将作大会报告。ACM CCS的全称是ACM Conference on Computer and Communications Security,已有30多年的历史,与IEEE S&P、USENIX Security、NDSS并列称为网络安全领域的四大国际学术会议,被中国计算机学会(CCF)列为A类会议。该会议收录的论文代表着相关领域的前沿学术研究成果,在业界具有广泛而深远的影响。展开更多
近日,西安电子科技大学网络与信息安全学院马建峰教授团队的最新研究成果“Watch the Rhythm:Breaking Privacy with Accelerometer at the Extremely-Low Sampling Rate of 5Hz”被ACM CCS 2024国际学术会议全文收录,并将作大会报告。A...近日,西安电子科技大学网络与信息安全学院马建峰教授团队的最新研究成果“Watch the Rhythm:Breaking Privacy with Accelerometer at the Extremely-Low Sampling Rate of 5Hz”被ACM CCS 2024国际学术会议全文收录,并将作大会报告。ACM CCS的全称是ACM Conference on Computer and Communications Security,已有三十多年的历史,与IEEE S&P、USENIX Security、NDSS并列称为网络安全领域的四大国际学术会议,被中国计算机学会(CCF)列为A类会议。该会议收录的论文代表着相关领域的前沿学术研究成果,在业界具有广泛而深远的影响。展开更多
在Photoshop CC 2017的教学方法是以任务驱动案例设计为核心,"火焰"字创意设计主要知识点为文字工具、编辑菜单中的变换、滤镜菜单中的"风"、"极坐标"等操作,针对实践操作过程中顺序不同创意出不用的设...在Photoshop CC 2017的教学方法是以任务驱动案例设计为核心,"火焰"字创意设计主要知识点为文字工具、编辑菜单中的变换、滤镜菜单中的"风"、"极坐标"等操作,针对实践操作过程中顺序不同创意出不用的设计作品。展开更多
As the demand for more efficient and adaptable power distribution systems intensifies, especially in rural areas, innovative solutions like the Capacitor-Coupled Substation with a Controllable Network Transformer (CCS...As the demand for more efficient and adaptable power distribution systems intensifies, especially in rural areas, innovative solutions like the Capacitor-Coupled Substation with a Controllable Network Transformer (CCS-CNT) are becoming increasingly critical. Traditional power distribution networks, often limited by unidirectional flow capabilities and inflexibility, struggle to meet the complex demands of modern energy systems. The CCS-CNT system offers a transformative approach by enabling bidirectional power flow between high-voltage transmission lines and local distribution networks, a feature that is essential for integrating renewable energy sources and ensuring reliable electrification in underserved regions. This paper presents a detailed mathematical representation of power flow within the CCS-CNT system, emphasizing the control of both active and reactive power through the adjustment of voltage levels and phase angles. A control algorithm is developed to dynamically manage power flow, ensuring optimal performance by minimizing losses and maintaining voltage stability across the network. The proposed CCS-CNT system demonstrates significant potential in enhancing the efficiency and reliability of power distribution, making it particularly suited for rural electrification and other applications where traditional methods fall short. The findings underscore the system's capability to adapt to varying operational conditions, offering a robust solution for modern power distribution challenges.展开更多
Chemokines play a paramount role in tumor progres-sion. In hepatocellular carcinoma (HCC) progression, chemokines and their receptors play an intricate role. Currently, chemokines and their receptors such as the CXCL1...Chemokines play a paramount role in tumor progres-sion. In hepatocellular carcinoma (HCC) progression, chemokines and their receptors play an intricate role. Currently, chemokines and their receptors such as the CXCL12-CXCR4 axis, CX3CL1-CX3CR1 axis and the CCL20-CCR6 axis have received much research attention. Although a large number of studies show that these axes are strongly associated with HCC, the exact mechanism by which these axes promote the growth and progression of HCC remains unknown. In this paper, several chemokines and their receptor interactions in HCC progression, growth and metastasis and immune response to HCC are reviewed.展开更多
The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their ne...The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their new roles in hepatocellular carcinoma(HCC). The chemokines and their receptors in the microenvironment influence the development of HCCby several aspects including:inflammation,effects on immune cells,angiogenesis,and direct effects on HCC cells. Regarding these aspects,pre-clinical research by targeting the chemokine system has yielded promising data,and these findings bring us new clues in the chemokine-based therapies for HCC.展开更多
Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates....Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates.In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines(CXCL1 to 17) are small(8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors(CXCR) 1 to 8.Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively.In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore,the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer.These pathways have been studied in tumor tissues(using immunohistochemistry or measuring mRNA levels)or serum [using enzyme-linked immuno sorbent assay(ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes themost recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.展开更多
AIM:To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma(HCC) in nude mice.METHODS:CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice.Beginning t...AIM:To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma(HCC) in nude mice.METHODS:CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice.Beginning two weeks after the challenge,tumor growth was measured every week for six weeks.The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples,and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme.A chemokine PCR array,comprised of 98 genes,was used to screen differential gene expressions,which were validated by Western blotting.Additionally,expression of identified chemokines was knocked-down by RNA interference,and the effect on tumor growth was assessed.RESULTS:Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage,neutrophil,and T cell(specifically helperand activated subsets)infiltration.Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase,suggestive of a proinflammatory phenotype.Fifty-one genes were identified in tumor tissues during the progression period,including 50that were overexpressed(including CXCL1,CXCL2 and CXCL3)and three that were underexpressed(CXCR1,Ifg and Actb).RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2,CXCL3and interleukin-1βprotein.CONCLUSION:These findings suggest that CXCL1plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.展开更多
Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is pre...Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.展开更多
Objective The aim of this study was to investigate the ability of Pref-1~+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes(MLNs) and the dynamic expression of related chemokines during the develo...Objective The aim of this study was to investigate the ability of Pref-1~+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes(MLNs) and the dynamic expression of related chemokines during the development of rat MLNs. Methods Immunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy(TEM) was used to observe the changes in ultrastructure of MLNs. Results Cells containing lipid droplets were found in all rat MLNs at embryonic day(E) 18.5, 2 and 6 weeks(w) after birth, and they were similar to fibroblastic reticular cells(FRCs) or follicular dendritic cells(FDCs) under TEM. Pref-1~+ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1(P 〈 0.01; r = 0.897). At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth(P 〈 0.05), while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth(P 〈 0.05). Conclusion Adipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.展开更多
AIM: To investigate the effect of secreted frizzledrelated proteins(s FRPs) on CXC chemokine expression in human mesenchymal stem cells(h MSCs).METHODS: CXC chemokines such as CXCL5 and CXCL8 are induced in h MSCs dur...AIM: To investigate the effect of secreted frizzledrelated proteins(s FRPs) on CXC chemokine expression in human mesenchymal stem cells(h MSCs).METHODS: CXC chemokines such as CXCL5 and CXCL8 are induced in h MSCs during differentiation with osteogenic differentiation medium(OGM) and may be involved in angiogenic stimulation during bone repair. h MSCs were treated with conditioned medium(CM) from L-cells expressing non-canonical Wnt5 a protein, or with control CM from wild type L-cells, or directly with s FRPs for up to 10 d in culture. m RNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose-(0-500 ng/m L) and time-response curves were generated for treatment with s FRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of si RNAs targeting specific frizzled receptors(Fzd)-2 and 5 or thereceptor tyrosine kinase-like orphan receptor-2(Ro R2) prior to treatment with s FRPs. RESULTS: CM from L-cells expressing Wnt5 a, a noncanonical Wnt, stimulated an increase in CXCL5 m RNA expression and protein secretion in comparison to control L-cell CM. s FRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the s FRPstimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four s FRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/m L. The largest increases in CXCL5 expression were seen from stimulation with s FRP1 or s FRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed s FRP1-induced phosphorylation of extracellular signal-regulated kinase(ERK)(p44/42) maximally at 5 min after s FRP1 addition, earlier than that found in OGM alone. Addition of a phospholipase C(PLC) inhibitor also prevented s FRPstimulated increases in CXCL8 m RNA. si RNA technology targeting the Fzd-2 and 5 and the non-canonical Fzd co-receptor Ro R2 also significantly decreased s FRP1/2-stimulated CXCL8 m RNA levels.CONCLUSION: CXC chemokine expression in h MSCs is controlled in part by s FRPs signaling through noncanonical Wnt involving Fzd2/5 and the ERK and PLC pathways.展开更多
文摘Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.
文摘Chemokines can be divided into four categories: α, β, γ, and δ. Chemokine α is related to neutrophil chemotaxis. Chemokine β is correlated with adsorption of monocytes,basophils, and eosinophils. Chemokine γ is mainly a lymphocyte chemokine. Function of chemokine δ remains unclear. Chemokines α and β are primarily related to occurrence and development of autoimmune thyroid disease. This study reviews chemokines and their receptors that are related to Graves’ disease and Hashimoto’s thyroiditis.
文摘近日,西安电子科技大学网络与信息安全学院李兴华教授团队的研究成果“PIC-BI:Practical and Intelligent Combinatorial Batch Identificationfor UAV Assisted Io T Networks”以及李金库教授团队的研究成果“Boosting Practical Control-Flow Integrity with Complete Field Sensitivity and Origin Awareness”同时被ACM CCS2024国际学术会议全文收录,并将作大会报告。ACM CCS的全称是ACM Conference on Computer and Communications Security,已有30多年的历史,与IEEE S&P、USENIX Security、NDSS并列称为网络安全领域的四大国际学术会议,被中国计算机学会(CCF)列为A类会议。该会议收录的论文代表着相关领域的前沿学术研究成果,在业界具有广泛而深远的影响。
文摘近日,西安电子科技大学网络与信息安全学院马建峰教授团队的最新研究成果“Watch the Rhythm:Breaking Privacy with Accelerometer at the Extremely-Low Sampling Rate of 5Hz”被ACM CCS 2024国际学术会议全文收录,并将作大会报告。ACM CCS的全称是ACM Conference on Computer and Communications Security,已有三十多年的历史,与IEEE S&P、USENIX Security、NDSS并列称为网络安全领域的四大国际学术会议,被中国计算机学会(CCF)列为A类会议。该会议收录的论文代表着相关领域的前沿学术研究成果,在业界具有广泛而深远的影响。
文摘As the demand for more efficient and adaptable power distribution systems intensifies, especially in rural areas, innovative solutions like the Capacitor-Coupled Substation with a Controllable Network Transformer (CCS-CNT) are becoming increasingly critical. Traditional power distribution networks, often limited by unidirectional flow capabilities and inflexibility, struggle to meet the complex demands of modern energy systems. The CCS-CNT system offers a transformative approach by enabling bidirectional power flow between high-voltage transmission lines and local distribution networks, a feature that is essential for integrating renewable energy sources and ensuring reliable electrification in underserved regions. This paper presents a detailed mathematical representation of power flow within the CCS-CNT system, emphasizing the control of both active and reactive power through the adjustment of voltage levels and phase angles. A control algorithm is developed to dynamically manage power flow, ensuring optimal performance by minimizing losses and maintaining voltage stability across the network. The proposed CCS-CNT system demonstrates significant potential in enhancing the efficiency and reliability of power distribution, making it particularly suited for rural electrification and other applications where traditional methods fall short. The findings underscore the system's capability to adapt to varying operational conditions, offering a robust solution for modern power distribution challenges.
基金Supported by Natural Science Key Program of the Education Department of Anhui Province, No. KJ2010A169
文摘Chemokines play a paramount role in tumor progres-sion. In hepatocellular carcinoma (HCC) progression, chemokines and their receptors play an intricate role. Currently, chemokines and their receptors such as the CXCL12-CXCR4 axis, CX3CL1-CX3CR1 axis and the CCL20-CCR6 axis have received much research attention. Although a large number of studies show that these axes are strongly associated with HCC, the exact mechanism by which these axes promote the growth and progression of HCC remains unknown. In this paper, several chemokines and their receptor interactions in HCC progression, growth and metastasis and immune response to HCC are reviewed.
基金Supported by National Science Foundation of China,No.31471147
文摘The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their new roles in hepatocellular carcinoma(HCC). The chemokines and their receptors in the microenvironment influence the development of HCCby several aspects including:inflammation,effects on immune cells,angiogenesis,and direct effects on HCC cells. Regarding these aspects,pre-clinical research by targeting the chemokine system has yielded promising data,and these findings bring us new clues in the chemokine-based therapies for HCC.
基金the Institute of Health Carlos Ⅲ(ISCⅢ)No.PI16/01800 and PIE16/00011
文摘Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates.In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines(CXCL1 to 17) are small(8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors(CXCR) 1 to 8.Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively.In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore,the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer.These pathways have been studied in tumor tissues(using immunohistochemistry or measuring mRNA levels)or serum [using enzyme-linked immuno sorbent assay(ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes themost recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.
基金Supported by Natural Science Foundation of China,No.81072954
文摘AIM:To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma(HCC) in nude mice.METHODS:CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice.Beginning two weeks after the challenge,tumor growth was measured every week for six weeks.The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples,and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme.A chemokine PCR array,comprised of 98 genes,was used to screen differential gene expressions,which were validated by Western blotting.Additionally,expression of identified chemokines was knocked-down by RNA interference,and the effect on tumor growth was assessed.RESULTS:Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage,neutrophil,and T cell(specifically helperand activated subsets)infiltration.Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase,suggestive of a proinflammatory phenotype.Fifty-one genes were identified in tumor tissues during the progression period,including 50that were overexpressed(including CXCL1,CXCL2 and CXCL3)and three that were underexpressed(CXCR1,Ifg and Actb).RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2,CXCL3and interleukin-1βprotein.CONCLUSION:These findings suggest that CXCL1plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda paraproyectos de investigación en saludPI-2007/32)+7 种基金"AsociaciónCastellana de Aparato Digestivo" (Beca ACADACAD/06)"Fundación de Investigación Médica Mutua Madrilea"(Beca Ayudas a la Investigación FMMM2548/2008),Spainsupported by a research grantfrom "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad deinvestigadores" MOV-2007_JI/18), Spainsupported by a research grant from "Instituto de SaludCarlos Ⅲ" (Contrato de apoyo a la investigación en el SNS"CA07/00157),Spain
文摘Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.
基金supported by the Project of Harbin Science and Technology Bureau of China[No.2017RAQXJ223]Graduate Students’Innovation Research Project of Harbin Medical University[No.YJSCX2017-6HYD]
文摘Objective The aim of this study was to investigate the ability of Pref-1~+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes(MLNs) and the dynamic expression of related chemokines during the development of rat MLNs. Methods Immunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy(TEM) was used to observe the changes in ultrastructure of MLNs. Results Cells containing lipid droplets were found in all rat MLNs at embryonic day(E) 18.5, 2 and 6 weeks(w) after birth, and they were similar to fibroblastic reticular cells(FRCs) or follicular dendritic cells(FDCs) under TEM. Pref-1~+ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1(P 〈 0.01; r = 0.897). At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth(P 〈 0.05), while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth(P 〈 0.05). Conclusion Adipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.
基金Supported by Merit Review Award from the United States,Department of Veterans Affairs Biomedical Laboratory Research and Development Service of the VA Office of Research and Development,No.I01BX000170
文摘AIM: To investigate the effect of secreted frizzledrelated proteins(s FRPs) on CXC chemokine expression in human mesenchymal stem cells(h MSCs).METHODS: CXC chemokines such as CXCL5 and CXCL8 are induced in h MSCs during differentiation with osteogenic differentiation medium(OGM) and may be involved in angiogenic stimulation during bone repair. h MSCs were treated with conditioned medium(CM) from L-cells expressing non-canonical Wnt5 a protein, or with control CM from wild type L-cells, or directly with s FRPs for up to 10 d in culture. m RNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose-(0-500 ng/m L) and time-response curves were generated for treatment with s FRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of si RNAs targeting specific frizzled receptors(Fzd)-2 and 5 or thereceptor tyrosine kinase-like orphan receptor-2(Ro R2) prior to treatment with s FRPs. RESULTS: CM from L-cells expressing Wnt5 a, a noncanonical Wnt, stimulated an increase in CXCL5 m RNA expression and protein secretion in comparison to control L-cell CM. s FRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the s FRPstimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four s FRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/m L. The largest increases in CXCL5 expression were seen from stimulation with s FRP1 or s FRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed s FRP1-induced phosphorylation of extracellular signal-regulated kinase(ERK)(p44/42) maximally at 5 min after s FRP1 addition, earlier than that found in OGM alone. Addition of a phospholipase C(PLC) inhibitor also prevented s FRPstimulated increases in CXCL8 m RNA. si RNA technology targeting the Fzd-2 and 5 and the non-canonical Fzd co-receptor Ro R2 also significantly decreased s FRP1/2-stimulated CXCL8 m RNA levels.CONCLUSION: CXC chemokine expression in h MSCs is controlled in part by s FRPs signaling through noncanonical Wnt involving Fzd2/5 and the ERK and PLC pathways.