作者机构：
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica &Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College;[CHEN Nai-hong; CHEN Ying] 中国医学科学院神经科学研究所
摘要：
Parkinson disease(PD) is a progressive degenerative disease of the nervous system,which is characterized by movement disorders,such as static tremor,rigidity,and bradykinesia in advanced patients.Gastrointestinal(GI) dysfunction,such as gastric dysmotility,constipation,and anorectic dysfunction,is common non-motor symptom in the early stage of PD.The progression of PD includes the degenerative loss of dopaminergic neurons and aggregation ofα-synuclein in the substantia nigra.Interestingly,both of them are also present in the enteric nervous system of PD patients.In this review,we describe the relationship between non-motor symptoms particularly GI dysfunction and the pathogenesis of PD,aiming to show the powerful evidences about the prion-like propagation of α-synuclein and support the hypothesis of gut-brain axis in PD.We then summarize the mechanism of the gut-brain axis and confirmα-synuclein as a potential target for drug design or new clinical treatment.
摘要：
Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the cerebrum.For the inflammation is a key progress at the initiation of ischemia and poststroke,and chemokines work as vital cytokines in inflammation,we focus the roles of chemokines in IS.Studies have shown cerebral ischemia is associated with marked induction of both CXC and CC chemokines which resulting in extensive leukocyte infiltration in the ischemic brain,and neutrophil infiltration may increase cerebral edema inducing injury in the ischemic area.In addition,chemokines also shows other functions such as promote neuroblast migration,hematogenous cell recruitment and functional brain repair.Thus,a similar chemokine ligand/chemokine receptor pair can mediate both beneficial and detrimental effects depending on the window of observation and pathophysiological conditions.This manuscript reviews the studies about chemokine-mediated effects in cerebral ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues.We also refer drug development based on the chemokines and clinical applications using chemokines as diagnostic or prognostic biomarkers in ischemic stroke.
作者机构：
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica &Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical Colege;[CHEN Nai-hong; ZHANG Zhao; CHU Shi-feng; CHEN Chen] 中国医学科学院神经科学研究所
关键词：
CHEMOKINE;cerebral;ISCHEMIA;ISCHEMIC;stroke
摘要：
OBJECTIVE To investigate the CKLF1 mediated expression of microglia/macrophage phenotypes in vitro and in vivo,discussing the involved pathway.METHODS In vitro,primary microglia isolated from mice cortex were used to study the effects of CKLF1 by qPCR analysis and immunofluorescence staining.In vivo,WT C57 and CKLF1 deficient mice were used to explore the effects of CKLF1.TTC staining,MRI and Nissl staining were applied to examine the infarction or neuron loss.Zea longa test was used to evaluate the neurological deficit of mice.Western blotting was used to investigate the changes of specific protein and discuss the involved pathway.We also used qPCR analysis and immunofluorescence staining for polarization markers to determine the effects of CKLF1.RESULTS CKLF1 could drive primary microglia to M1 phenotype for 24 h stimulation in primary microglia.In mice transient ischemic stroke model,CKLF1 attenuated ischemic injury,and accompanied by promoting microglia/macrophage toward M1 polarization.Increased expression of pro-inflammatory cytokines and decreased expression of neurotropic factors and anti-inflammatory cytokines were observed in mice subjected to cerebral ischemia with C27.Moreover,NF-κB activation enhancement was detected in C27 modulated M1 polarization effects.CONCLUSION CKLF1 is an important mediator of driving M1 phenotype of microglia/macrophage at early stage of cerebral ischemic injury,contributing to aggravation of cerebral ischemia injury,which closely related to microglia/macrophage M1 polarization guided inflammatory response.Targeting CKLF1 has the potential to treat ischemic stroke.
摘要：
IMM-H004 [7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin] is a novel derivative of coumarin, which played neuroprotective roles in brain ischemia in rats in previous studies. Although antiapoptosis and improving synapsis structure were proved, the effects and mechanisms of IMM-H004 in brain ischemia need further study. In this paper, the effect of IMM-H004 on H2O2-induced neurotoxicity in pheochromocytoma (PC12) cells was researched. Morphological observation, MTT method and PI/Hoechst staining were used to indicate cell viability and apoptosis. JC-1 and DCFH-DA were used to test mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), respectively. The antioxidative activity was detected by Glutathione (GSH) and Total Antioxidant Capacity (TAC) Assay kits. Western blot was used to test apoptosis related proteins. Our results showed that treatment with 1-10 μM IMM-H004 markedly increased cell viability and decreased cell apoptosis induced by H2O2. Moreover, 1-10 μM IMM-H004 could enhance MMP and protect mitochondrial function. 1-10 μM IMM-H004 also could lower the ROS and raise the GSH and TAC level. Furthermore, 1-10 μM IMM-H004 could decrease the ratio of Bax/Bcl-2 and increase the ratio of p-AKT/AKT, which were related to apoptosis and survival. All these indicated that IMM-H004 protects PC12 cells against H2O2-induced neurotoxicity. Antioxidative and antiapoptosis may be the mechanisms of IMM-H004 in brain ischemia. These studies indicate that IMM-H004 might be a potential drug for treatment brain ischemia.
摘要：
Ample evidence shows that Parkinson's disease (PD) is more than simply a central nervous system (CNS) disorder: the immune system appears to participate in PD pathogenesis. Extracellular misfolded alpha-synuclein (alpha-syn) may trigger an inflammatory response in the brain. Abnormal immune responses are involved in the development of PD, but little is known about the relationship between the thymus malfunction and the pathogenesis of PD. The present study investigated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced impairment in thymus and explored possible mechanisms involved in PD pathogenesis. After subcutaneous injection of MPTP (25mg/kg) every 4days for 40-days, immune responses became unbalanced, with increased IL-1beta concentrations. On histopathology, mice treated with MPTP displayed pathological involution and damaged ultrastructure of the thymus. Both the PD-related oligomeric alpha-synuclein and oxidative stress related nitrated-alpha-synuclein (Tyr125, Tyr133) in mice treated with MPTP were elevated. Correspondingly, oxidative stress damage was detected in the form of increased 8-hydroxyguanosine staining. Moreover, MPTP significantly increased expression of caspase-8, NF-kappaB, NLPR3, and caspase-1 in the thymus. These results suggested that MPTP was toxic to mouse thymus via a mechanism involving the NF-kappaB and NLRP3 inflammasome pathway. These results suggested that environmental factors may lead to pathological changes in the thymus that are similar to those in the central nervous system. A disordered thymus might take part in the development of PD, and its enhanced immune response might promote the degenerative changes in the brain.
摘要：
Major depressive disorder (MDD) is a chronic and debilitating illness that affects over 350 million people worldwide; however, current treatments have failed to cure or prevent the progress of depression. Increasing evidence suggests a crucial role for connexins in MDD. In this review, we have summarised recent accomplishments regarding the role of connexins, gap junctions, and hemichannels in the aetiology of MDD, and discussed the limitations of current research. A blockage of gap junctions or hemichannels induces depressive behaviour. Possible underlying mechanisms include the regulation of neurosecretory functions and synaptic activity by gap junctions and hemichannels. Gap junctions are functionally inhibited under stress conditions. Conversely, hemichannel permeability is increased. Antidepressants inhibit hemichannel permeability; however, they have contrasting effects on the function of gap junctions under normal conditions and can protect them against stress. In conclusion, the blockage of hemichannels concurrent with improvements in gap junction functionality might be potential targets for depression treatment. (C) 2018 Elsevier B.V. and ECNP. All rights reserved.
摘要：
Objective To assess the environment of Hunan production base of lilium lancifolium by the index of the soil,irrigation water and air quality.Methods The content distribution characteristics of cadmium(Cd),chromium(Cr),mercury(Hg),arsenic(As),plumbum(Pb)and cuprum(Cu)in Longshan region soils and irrigation water of ilium lancifolium base in Hunan province were analyzed.The six basic indexes of SO2,NO2,CO,O3,PM10 and PM2.5 in the atmospheric environment of Longshan lilium lancifolium base were determined.The environmental quality in research area was assessed by using single pollution index method,comprehensive pollution index method and potential ecological risk index.Results The content of Cd,chromium Cr,Hg,As,Pb and Cu of soil were in the range of 0.16~0.29,2.30~6.63,0.08~0.30,10.33~26.44,2.00~11.60,10.60~36.44 mg/kg;the contents of Pb,Cd,Cr,Cu,As and Hg in the irrigated area were 0.000 2~0.002 0袁0.000 2~0.000 9袁not detected,0~0.000 1,0.000 3~0.001 0 and 0.000 1~0.000 5 mg/L.The annual average values of SO2,NO2,PM10 and PM2.5 in the local atmospheric environment were 16,13,60 and 34 g/m3,respectively.The average value of CO(24 hours)was 0.9 mg/m3,and the maximum 8 hours for O3 was 94滋g/m3.According to the comprehensive pollution index and potential ecological risk index method,the average pollution level in Longshan area is in the security level,the pollution level is clean level,and the ecological risk grade is grade A(low).Conclusion Longshan has excellent production environment suitable for the growth of lilium lancifolium.However,the Pi of Cd,Hg and As in some soil samples are more than 1,or close to the critical value of 1,which has some potential ecological risk.
作者机构：
College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[张钊] Institute of Material Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100050, China;[张欣] College of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan, 030619, China;[姜懿纳; 陈乃宏; 罗林明; 阳松威] College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China, Institute of Material Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100050, China
作者机构：
[罗林明; 黄绍国; 陈乃宏; 裴刚; Qin, Li; 周小江] College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China;[罗林明; 黄绍国; 陈乃宏; 裴刚; 周小江] Engineering Technology Research Center of Standardization and Function of Traditional Chinese Medicine Decoction Pieces in Hunan Province, Changsha 410208, China;[陈乃宏] Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
通讯机构：
College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
