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
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
T/CMA CC 045-2020《计量电子原始记录通用规范》实施以来,其在规范计量电子原始记录、提高工作效率、提高质量控制水平、提高证书的可靠性等方面都有着积极的作用。但是该标准也存在一定的短板,未能统一标准的文件格式,对于电子记录防...T/CMA CC 045-2020《计量电子原始记录通用规范》实施以来,其在规范计量电子原始记录、提高工作效率、提高质量控制水平、提高证书的可靠性等方面都有着积极的作用。但是该标准也存在一定的短板,未能统一标准的文件格式,对于电子记录防伪加密要求偏低,对于不确定度的覆盖不全面,对新技术的支持略有不足,这些需要在今后的实践中加以修正,以便更好地服务于计量行业的发展。展开更多
Hemoglobinosis C occurs mainly in Africa and America with a high frequency in West Africa. In Senegal, homozygous hemoglobinopathy CC constitutes a very rare profile of which only 3 cases are followed in the clinical ...Hemoglobinosis C occurs mainly in Africa and America with a high frequency in West Africa. In Senegal, homozygous hemoglobinopathy CC constitutes a very rare profile of which only 3 cases are followed in the clinical hematology department of Dakar. The 1<sup>st</sup> case is a 49-year-old female patient, with notion of 1<sup>st</sup> degree consanguinity, and a long history of abdominal pain who presented a poorly tolerated anemic syndrome and splenomegaly. The biological assessment showed moderate anemia (7.6 g/dL) with microcytic hypochromia and a CC profile (HbC = 99.2%;HbA2 = 0.8%) on hemoglobin electrophoresis. The second case was a 22-year-old female patient with a notion of 2<sup>nd</sup> degree consanguinity who presented a Chauffard triad. The haemogram showed mild anaemia (11 g/dL), microcytic and hypochromic. Hemoglobin electrophoresis confirmed a CC profile (HbC = 95.3%;HbA2 = 4.7%). The third patient was 27 years old, with a history of diffuse abdominal pain and 2<sup>nd</sup> degree consanguinity. The haemogram and haemoglobin electrophoresis confirmed the CC profile (HbC = 94.6%;HbA2 = 5.4%). The negativity of the Emmel test in front of this presentation suggestive of sickle cell disease means that this type of hemoglobinopathy is diagnosed late in our regions. We therefore recommend the systematic performance of hemoglobin electrophoresis in the presence of any chronic hemolytic anemia.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
Spinal cord injury causes accumulation of a large number of leukocytes at the lesion site where they contribute to excessive inflammation.Overproduced chemokines are responsible for the migratory process of the leukoc...Spinal cord injury causes accumulation of a large number of leukocytes at the lesion site where they contribute to excessive inflammation.Overproduced chemokines are responsible for the migratory process of the leukocytes,but the regulatory mechanism underlying the production of chemokines from resident cells of the spinal cord has not been fully elucidated.We examined the protein levels of macrophage migration inhibitory factor and chemokine C-C motif chemokine ligand 2 in a spinal cord contusion model at different time points following spinal cord injury.The elevation of macrophage migration inhibitory factor at the lesion site coincided with the increase of chemokine C-C motif chemokine ligand 2 abundance in astrocytes.Stimulation of primary cultured astrocytes with different concentrations of macrophage migration inhibitory factor recombinant protein induced chemokine C-C motif chemokine ligand 2 production from the cells,and the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine attenuated the stimulatory effect.Further investigation into the underlying mechanism on macrophage migration inhibitory factor-mediated astrocytic production of chemokine C-C motif chemokine ligand 2 revealed that macrophage migration inhibitory factor activated intracellular JNK signaling through binding with CD74 receptor.Administration of the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine following spinal cord injury resulted in the reduction of chemokine C-C motif chemokine ligand 2-recruited microglia/macrophages at the lesion site and remarkably improved the hindlimb locomotor function of rats.Our results have provided insights into the functions of astrocyte-activated chemokines in the recruitment of leukocytes and may be beneficial to develop interventions targeting chemokine C-C motif chemokine ligand 2 for neuroinflammation after spinal cord injury.展开更多
Classically,chemokines were described as small proteins driving leukocyte migration.Nonetheless,more and more studies are showing the great variety of cell functions and tissues in which they participate,including neu...Classically,chemokines were described as small proteins driving leukocyte migration.Nonetheless,more and more studies are showing the great variety of cell functions and tissues in which they participate,including neural cells.During the last years,research has highlighted the importance of chemokines in the nervous system,governing a wide range of processes (MesquidaVeny et al.,2021).This is evidenced for example by the crucial role played by CXCL12 during cortical development,or the homeostatic role of neuronal CX3CL1,preventing microglial activation.We are now certain that many chemokines and their receptors are widely expressed in neurons,and growing evidence has shown them as fundamental players in direct neuronal communication,both during homeostasis and after insult.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
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
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
Theinvestigation of physicometallurgicalphenomena forthe CC formingof WCP/ Fe Ccom posites wasperformed. Resultsshow that underthe patentcondition, WCP/ Fe Ccomposite surfacelayerof16 20 m m heavycross sectio...Theinvestigation of physicometallurgicalphenomena forthe CC formingof WCP/ Fe Ccom posites wasperformed. Resultsshow that underthe patentcondition, WCP/ Fe Ccomposite surfacelayerof16 20 m m heavycross sectioncan beacquiredintheoutsideofa hollow cylin der. The surface of CTC particlescould be partially dissolved by Fe containing melt. Thefineshortstick like WCcrystallitesarein situseparated neartothesurfaceof CTC particles.Far from the CTC particles,someseparated, finetungsten carbidecrystallitesand Fe, W,Mo and Cretc. containing web composite carbides, are distributed on the matrix of WCP/ Fe Ccomposite. Fe Calloy matrix of the hollow composite cylinder is alloyed in differenthigh levels.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T/CMA CC 045-2020《计量电子原始记录通用规范》实施以来,其在规范计量电子原始记录、提高工作效率、提高质量控制水平、提高证书的可靠性等方面都有着积极的作用。但是该标准也存在一定的短板,未能统一标准的文件格式,对于电子记录防伪加密要求偏低,对于不确定度的覆盖不全面,对新技术的支持略有不足,这些需要在今后的实践中加以修正,以便更好地服务于计量行业的发展。
文摘Hemoglobinosis C occurs mainly in Africa and America with a high frequency in West Africa. In Senegal, homozygous hemoglobinopathy CC constitutes a very rare profile of which only 3 cases are followed in the clinical hematology department of Dakar. The 1<sup>st</sup> case is a 49-year-old female patient, with notion of 1<sup>st</sup> degree consanguinity, and a long history of abdominal pain who presented a poorly tolerated anemic syndrome and splenomegaly. The biological assessment showed moderate anemia (7.6 g/dL) with microcytic hypochromia and a CC profile (HbC = 99.2%;HbA2 = 0.8%) on hemoglobin electrophoresis. The second case was a 22-year-old female patient with a notion of 2<sup>nd</sup> degree consanguinity who presented a Chauffard triad. The haemogram showed mild anaemia (11 g/dL), microcytic and hypochromic. Hemoglobin electrophoresis confirmed a CC profile (HbC = 95.3%;HbA2 = 4.7%). The third patient was 27 years old, with a history of diffuse abdominal pain and 2<sup>nd</sup> degree consanguinity. The haemogram and haemoglobin electrophoresis confirmed the CC profile (HbC = 94.6%;HbA2 = 5.4%). The negativity of the Emmel test in front of this presentation suggestive of sickle cell disease means that this type of hemoglobinopathy is diagnosed late in our regions. We therefore recommend the systematic performance of hemoglobin electrophoresis in the presence of any chronic hemolytic anemia.
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.
基金supported by the China Postdoctoral Science Foundation,No.2020M681689(to YMH)the Basic Scientific Research Projects of Nantong,Nos.JC2020015(to HX)and JC2020041(to YMH)。
文摘Spinal cord injury causes accumulation of a large number of leukocytes at the lesion site where they contribute to excessive inflammation.Overproduced chemokines are responsible for the migratory process of the leukocytes,but the regulatory mechanism underlying the production of chemokines from resident cells of the spinal cord has not been fully elucidated.We examined the protein levels of macrophage migration inhibitory factor and chemokine C-C motif chemokine ligand 2 in a spinal cord contusion model at different time points following spinal cord injury.The elevation of macrophage migration inhibitory factor at the lesion site coincided with the increase of chemokine C-C motif chemokine ligand 2 abundance in astrocytes.Stimulation of primary cultured astrocytes with different concentrations of macrophage migration inhibitory factor recombinant protein induced chemokine C-C motif chemokine ligand 2 production from the cells,and the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine attenuated the stimulatory effect.Further investigation into the underlying mechanism on macrophage migration inhibitory factor-mediated astrocytic production of chemokine C-C motif chemokine ligand 2 revealed that macrophage migration inhibitory factor activated intracellular JNK signaling through binding with CD74 receptor.Administration of the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine following spinal cord injury resulted in the reduction of chemokine C-C motif chemokine ligand 2-recruited microglia/macrophages at the lesion site and remarkably improved the hindlimb locomotor function of rats.Our results have provided insights into the functions of astrocyte-activated chemokines in the recruitment of leukocytes and may be beneficial to develop interventions targeting chemokine C-C motif chemokine ligand 2 for neuroinflammation after spinal cord injury.
基金HDAC3-EAE-SCI Project with ref.PID2020-119769RA-I00 from MCIN/AEI/10.13039/501100011033 to AH。
文摘Classically,chemokines were described as small proteins driving leukocyte migration.Nonetheless,more and more studies are showing the great variety of cell functions and tissues in which they participate,including neural cells.During the last years,research has highlighted the importance of chemokines in the nervous system,governing a wide range of processes (MesquidaVeny et al.,2021).This is evidenced for example by the crucial role played by CXCL12 during cortical development,or the homeostatic role of neuronal CX3CL1,preventing microglial activation.We are now certain that many chemokines and their receptors are widely expressed in neurons,and growing evidence has shown them as fundamental players in direct neuronal communication,both during homeostasis and after insult.
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 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.
文摘Theinvestigation of physicometallurgicalphenomena forthe CC formingof WCP/ Fe Ccom posites wasperformed. Resultsshow that underthe patentcondition, WCP/ Fe Ccomposite surfacelayerof16 20 m m heavycross sectioncan beacquiredintheoutsideofa hollow cylin der. The surface of CTC particlescould be partially dissolved by Fe containing melt. Thefineshortstick like WCcrystallitesarein situseparated neartothesurfaceof CTC particles.Far from the CTC particles,someseparated, finetungsten carbidecrystallitesand Fe, W,Mo and Cretc. containing web composite carbides, are distributed on the matrix of WCP/ Fe Ccomposite. Fe Calloy matrix of the hollow composite cylinder is alloyed in differenthigh levels.