Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spi...Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral sur-face of T13. Electroacupuncture was used to stimulate the bilateralZusanlipoint （ST36） and Neiting point （ST44） for 14 days. Compared with control animals, blood lfow in the ifrst lumbar vertebra （L1） was noticeably increased in rats given electroacupuncture. Microvessel density in the T13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved signiifcantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.展开更多
Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of th...Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease severity.The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in injury.This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.展开更多
Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dep...Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP’s ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP’s ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP’s ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.展开更多
Alzheimer’s disease (AD) is the most common form of dementia which mostly affects persons younger than 65 years old. Mounting findings showed that amyloid-β(Aβ) peptides, oxidative stress, neuroinfl...Alzheimer’s disease (AD) is the most common form of dementia which mostly affects persons younger than 65 years old. Mounting findings showed that amyloid-β(Aβ) peptides, oxidative stress, neuroinflammation and insulin resistance may play central role in the pathogenesis of AD. There are very many methods to slow it through affecting these aforementioned factors. However, more efficient prevention of the progression of AD is still ambiguous. Fibroblast growth factor 21 (FGF21) is an endocrine hormone that is expressed by several organs. It increases insulin sensitivity and regulates lipid metabolism and energy homeostasis. Emerging evidence demonstrates that FGF21 has potential effects in the brain involving metabolic regulation, neuroprotection and cognition. Hence, we hypothesize that FGF21 may be a protective factor in AD by attenuating Aβ generation, inflammation, oxidative stress, and insulin resistance. Our hypothesis will shed new light on the understanding of pathogenesis of AD and help to find a new way to prevent the genesis and progress of AD.展开更多
目的探讨炎症条件的动物输注贮存红细胞对巨噬细胞(BMDMs)的调节作用以及贮存红细胞输注与细菌感染引发炎症反应的关系。方法将6~8周龄成年雄性C57BL/6小鼠[(18~22)g/只]40只随机均分为实验组和实验对照组(对照组),均通过动物尾静脉注...目的探讨炎症条件的动物输注贮存红细胞对巨噬细胞(BMDMs)的调节作用以及贮存红细胞输注与细菌感染引发炎症反应的关系。方法将6~8周龄成年雄性C57BL/6小鼠[(18~22)g/只]40只随机均分为实验组和实验对照组(对照组),均通过动物尾静脉注射铜绿假单胞菌200μL/只,并使用吸入式麻醉剂异氟烷(1%~3%)麻醉后,通过小鼠眼后静脉丛,实验组输注鼠源贮存悬浮红细胞(>14 d)400μL/只、对照组每只输注等量新鲜悬浮红细胞(贮存<24 h);于输注后2、4、8 h脱就猝死各结束2组小鼠生命5只,摘取鼠肝,体外培养铜绿假单胞菌感染(200μL/只)小鼠的股骨、胫骨骨髓来源的BMDMs,流式细胞术检测BMDMs中分化簇86(CD86)、分化簇197(CD197)[巨噬细胞1型(M1)基因特异性标志物]、分化簇209(CD209)[巨噬细胞2型(M2)基因特异性标记]表达水平,实时荧光定量PCR(qRT-PCR)法检测小鼠肝脏F4/80、M1、M2基因表达水平,并使用SPSS17.0统计学软件分析数据。结果实验组与对照组BMDMs中CD86和CD197的表达(%)分别为8688±1.01 vs 79.24±2.65、38.59±3.73 vs 25.95±0.86(P<0.05),CD209(%)为23.88±2.23 vs 21.91±3.58(P>0.05)。输注红细胞后2、4 h,小鼠肝F4/80基因表达水平实验组和对照组分别为1.83±0.11 vs 0.75±0.06、0.46±0.06 vs 0.33±0.06(P<0.05),8 h后分别为0.33±0.03 vs 0.35±0.05(P>0.05);输注红细胞2、4、8 h,小鼠肝M1基因中诱导型一氧化氮合酶(iNOS)基因表达水平实验组和对照组分别为3.44±0.20 vs 2.46±0.08、9.25±0.55 vs 2.67±0.12、2.80±0.08 vs 2.39±0.01,肿瘤坏死因子-α(TNF-α)分别为1.69±0.22 vs 1.13±0.03、1.44±0.24 vs 0.96±0.09、1.31±0.05 vs 0.96±0.06,单核细胞趋化蛋白1(MCP1)分别为4.96±0.08 vs 4.28±0.27、4.63±0.04 vs 2.07±0.09、2.28±0.19 vs 1.33±0.03(P<0.05);M2基因中精氨酸1(Arg1)基因表达水平实验组和对照组分别为0.81±0.21 vs 0.82±0.18、0.66±0.11 vs 0.58±0.09、0.39±0.17 vs 0.37±0.15,甘露糖受体C型2(Mrc2)分�展开更多
AIM： To study the association between inflammatory bowel disease （IBD） and genetic variations in eosinophil protein X （EPX） and eosinophil cationic protein （ECP）. METHODS： DNA was extracted from ethylene diami...AIM： To study the association between inflammatory bowel disease （IBD） and genetic variations in eosinophil protein X （EPX） and eosinophil cationic protein （ECP）. METHODS： DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn＇s disease （CD）, 592 with ulcerative colitis （UC） and 300 healthy subjects. The EPX405 （G 〉 C, rs2013109）, ECP434 （G 〉 C, rs2073342） and ECP562 （G 〉 C, rs2233860） gene polymorphisms were analysed, by the 5＇-nuclease allelic discrimination assay. For de- termination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylam- monium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent as- say. The intracellular content of ECP was analysed with the UniCAP system as described by the manufacturer. Statistical tests for calculations of results were χ2 test, Fisher＇s exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P 〈 0.05 were considered statistically significant.RESULTS： The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years （n = 57） was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject＇s genotype frequencies of ECP434 （GG = 57%, GC = 38%, CC = 5%; P = 0.010） and ECP562 （GG = 68%, GC = 29%,CC = 3%; P = 0.009）. The genotype frequencies for females, with an age of dis- ease onset of ≥ 45 years with CD （n = 62）, was for the ECP434 and ECP562 genotypes GG = 37%, GC =52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 （P = 0.010） and ECP562 （P = 0.013）. The intracellular protein concen- tration of EPX and ECP was calculated in μg/10^6 eosi- nophils and then展开更多
基金supported by the National Natural Science Foundation of China,No.31372473,30871886the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality of China,No.PHR201107134the 2012 Scientific Research Quality Raising Funds of Beijing University of Agriculture of China,No.PXM2012_014207_000010
文摘Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral sur-face of T13. Electroacupuncture was used to stimulate the bilateralZusanlipoint （ST36） and Neiting point （ST44） for 14 days. Compared with control animals, blood lfow in the ifrst lumbar vertebra （L1） was noticeably increased in rats given electroacupuncture. Microvessel density in the T13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved signiifcantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.
基金Supported by National Institute of Health,NIH DK 43785
文摘Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease severity.The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in injury.This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.
基金Supported by Crohn’s and Colitis Foundation of Canada,No.11883 1486 RR 0001Natural Science and Engineering Re-search Council and the Intestinal Diseases Education Awareness Society,No.86435 5557 RR0001
文摘Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP’s ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP’s ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP’s ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.
文摘[目的]探索骨髓间充质干细胞来源的外泌体对类风湿关节炎滑膜成纤维细胞(Rheumatoid arthritis synovial fibroblasts,RA-FLS)的作用以及相关作用机制,以期为类风湿关节炎治疗提供新思路。[方法]将类风湿关节炎滑膜成纤维细胞分为4组,分别用0、1、3、5μmol/L的人骨髓间充质干细胞来源的外泌体进行处理。MTT实验和流式细胞术评估细胞损伤情况;Transwell实验分析细胞迁移能力;ELISA试剂检测炎症因子的含量;蛋白免疫印迹实验分析p38蛋白激活情况。[结果]骨髓间充质干细胞来源的外泌体能够降低RA-FLS迁移能力(198.56±10.89 vs 31.27±1.66),并能促进RA-FLS发生凋亡(6.26%±0.09%vs 23.56%±1.21%)。人骨髓间充质干细胞来源的外泌体还能减少RA-FLS分泌的炎症细胞因子。人骨髓间充质干细胞来源的外泌体能够抑制p38蛋白磷酸化(0.89±0.02 vs 0.11±0.01)。[结论]人骨髓间充质干细胞来源的外泌体能够抑制RA-FLS生长和转移,抑制RA-FLS分泌炎症因子,这些作用与抑制p38 MAPK激活有关。
文摘Alzheimer’s disease (AD) is the most common form of dementia which mostly affects persons younger than 65 years old. Mounting findings showed that amyloid-β(Aβ) peptides, oxidative stress, neuroinflammation and insulin resistance may play central role in the pathogenesis of AD. There are very many methods to slow it through affecting these aforementioned factors. However, more efficient prevention of the progression of AD is still ambiguous. Fibroblast growth factor 21 (FGF21) is an endocrine hormone that is expressed by several organs. It increases insulin sensitivity and regulates lipid metabolism and energy homeostasis. Emerging evidence demonstrates that FGF21 has potential effects in the brain involving metabolic regulation, neuroprotection and cognition. Hence, we hypothesize that FGF21 may be a protective factor in AD by attenuating Aβ generation, inflammation, oxidative stress, and insulin resistance. Our hypothesis will shed new light on the understanding of pathogenesis of AD and help to find a new way to prevent the genesis and progress of AD.
文摘目的探讨炎症条件的动物输注贮存红细胞对巨噬细胞(BMDMs)的调节作用以及贮存红细胞输注与细菌感染引发炎症反应的关系。方法将6~8周龄成年雄性C57BL/6小鼠[(18~22)g/只]40只随机均分为实验组和实验对照组(对照组),均通过动物尾静脉注射铜绿假单胞菌200μL/只,并使用吸入式麻醉剂异氟烷(1%~3%)麻醉后,通过小鼠眼后静脉丛,实验组输注鼠源贮存悬浮红细胞(>14 d)400μL/只、对照组每只输注等量新鲜悬浮红细胞(贮存<24 h);于输注后2、4、8 h脱就猝死各结束2组小鼠生命5只,摘取鼠肝,体外培养铜绿假单胞菌感染(200μL/只)小鼠的股骨、胫骨骨髓来源的BMDMs,流式细胞术检测BMDMs中分化簇86(CD86)、分化簇197(CD197)[巨噬细胞1型(M1)基因特异性标志物]、分化簇209(CD209)[巨噬细胞2型(M2)基因特异性标记]表达水平,实时荧光定量PCR(qRT-PCR)法检测小鼠肝脏F4/80、M1、M2基因表达水平,并使用SPSS17.0统计学软件分析数据。结果实验组与对照组BMDMs中CD86和CD197的表达(%)分别为8688±1.01 vs 79.24±2.65、38.59±3.73 vs 25.95±0.86(P<0.05),CD209(%)为23.88±2.23 vs 21.91±3.58(P>0.05)。输注红细胞后2、4 h,小鼠肝F4/80基因表达水平实验组和对照组分别为1.83±0.11 vs 0.75±0.06、0.46±0.06 vs 0.33±0.06(P<0.05),8 h后分别为0.33±0.03 vs 0.35±0.05(P>0.05);输注红细胞2、4、8 h,小鼠肝M1基因中诱导型一氧化氮合酶(iNOS)基因表达水平实验组和对照组分别为3.44±0.20 vs 2.46±0.08、9.25±0.55 vs 2.67±0.12、2.80±0.08 vs 2.39±0.01,肿瘤坏死因子-α(TNF-α)分别为1.69±0.22 vs 1.13±0.03、1.44±0.24 vs 0.96±0.09、1.31±0.05 vs 0.96±0.06,单核细胞趋化蛋白1(MCP1)分别为4.96±0.08 vs 4.28±0.27、4.63±0.04 vs 2.07±0.09、2.28±0.19 vs 1.33±0.03(P<0.05);M2基因中精氨酸1(Arg1)基因表达水平实验组和对照组分别为0.81±0.21 vs 0.82±0.18、0.66±0.11 vs 0.58±0.09、0.39±0.17 vs 0.37±0.15,甘露糖受体C型2(Mrc2)分�
基金Supported by Grants from the Swedish Research Council-Medicinethe Hedlunds Foundation and from the Medical Faculty,Uppsala University,Uppsala,Sweden
文摘AIM： To study the association between inflammatory bowel disease （IBD） and genetic variations in eosinophil protein X （EPX） and eosinophil cationic protein （ECP）. METHODS： DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn＇s disease （CD）, 592 with ulcerative colitis （UC） and 300 healthy subjects. The EPX405 （G 〉 C, rs2013109）, ECP434 （G 〉 C, rs2073342） and ECP562 （G 〉 C, rs2233860） gene polymorphisms were analysed, by the 5＇-nuclease allelic discrimination assay. For de- termination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylam- monium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent as- say. The intracellular content of ECP was analysed with the UniCAP system as described by the manufacturer. Statistical tests for calculations of results were χ2 test, Fisher＇s exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P 〈 0.05 were considered statistically significant.RESULTS： The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years （n = 57） was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject＇s genotype frequencies of ECP434 （GG = 57%, GC = 38%, CC = 5%; P = 0.010） and ECP562 （GG = 68%, GC = 29%,CC = 3%; P = 0.009）. The genotype frequencies for females, with an age of dis- ease onset of ≥ 45 years with CD （n = 62）, was for the ECP434 and ECP562 genotypes GG = 37%, GC =52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 （P = 0.010） and ECP562 （P = 0.013）. The intracellular protein concen- tration of EPX and ECP was calculated in μg/10^6 eosi- nophils and then
