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
Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hyp...Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.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 correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 （GG = 4.65, GC = 5.93, and CC = 6.57） and for ECP in the patients with the GG genotype of EPX405 （GG = 2.70, GC = 2.47 and CC = 1.90）. ANOVA test demonstrated a difference in intracellular protein content for EPX （P = 0.009） and ECP （P = 0.022）. The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference be- tween haplotype distributions for the females with CD （P = 0.003）. The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype （34 years） and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype （21 years）. For males with UC there was also a difference between the highest and lowest age of the disease on- set （EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009）. The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dys- plasia/cancer was 2.5 （95%CI： 1.2-5.4, P = 0.01） and 2.5 （95%CI： 1.1-5.4, P = 0.02） respectively, compared to patients carrying the GG-genotypes.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
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.
文摘Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.
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 correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 （GG = 4.65, GC = 5.93, and CC = 6.57） and for ECP in the patients with the GG genotype of EPX405 （GG = 2.70, GC = 2.47 and CC = 1.90）. ANOVA test demonstrated a difference in intracellular protein content for EPX （P = 0.009） and ECP （P = 0.022）. The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference be- tween haplotype distributions for the females with CD （P = 0.003）. The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype （34 years） and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype （21 years）. For males with UC there was also a difference between the highest and lowest age of the disease on- set （EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009）. The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dys- plasia/cancer was 2.5 （95%CI： 1.2-5.4, P = 0.01） and 2.5 （95%CI： 1.1-5.4, P = 0.02） respectively, compared to patients carrying the GG-genotypes.
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.
