AIM:To determine whether limb remote ischemic post-conditioning (LRIC) protects against high-intraocular-pressure (IOP)-induced retinal injury, and to identify underlying molecular mechanisms.METHODS:In mice, IOP was increased to 110 mm Hg for 50min and LRIC applied to the unilateral leg for three occlusion cycles (5min/release). Three animal groups (control, high IOP, and high IOP+LRIC) were arranged in this study. Plasma was collected from LRIC treated mice. Retinal histology, oxidative stress were determined by histological section staining and chemical kit. C/EBP homologous protein (CHOP), and Iba-1 parameters were evaluated by immunofluorescent staining and Western blot.RESULTS:The data showed that LRIC treatment alleviated the retinal histological disorganization and ganglion cell loss induced by high IOP. The CHOP, Iba-1 expression and oxidative stress marker also were inhibited by LRIC treatment. To further explore underlying mechanisms, plasma from LRIC treated animals was intravenously transfused into high-IOP animals. The results showed plasma injection decreased caspase 9 expression and DHE staining signals compared with that in high IOP retinas.CONCLUSION:These data suggest that LRIC treatments exert retinal protective effects against high-IOP injury. Endogenous humoral factors release into the circulation by LRIC may contribute to homeostatic protection by reducing monocyte infiltration and/or microglia activation.

Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI-NI, PDIB-NI, and PDIC-NI, are developed and it is found that the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC-NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell, presents solid evidence for LUMO energy level determining endogenous ROS burst. Stirringly, PDIC-NI-induced ROS generation arouses enhanced mitochondrial oxidative stress and concurrently activates immunogenic cell death (ICD), which not only efficiently kills lung tumor cells but also reprograms immunosuppressive tumor microenvironment, including the cytokine secretion, dendritic cell maturation, as well as cytotoxic T lymphocytes activation, to inhibit the growth of xenografted and metastasis tumor, presenting a proof-of-concept demonstration of perylene that acts as an integrated therapeutic agent to well realize hypoxia-activated chemotherapy with ICD-induced immunotherapy on lung cancer.

树突棘为分布于人脑的大多数神经元树突上覆盖的一些小突起,它是构成神经元之间突触连接的主要部位.树突棘的结构、形态和密度等在患有神经系统智力障碍性疾病时都会发生相应的改变.我们选取部分与之相关的文献进行综述,以期为相关方面研究提供思路.

为更好地使陈列标本服务于"人体解剖学"教学,针对解剖楼内标本摆放杂乱、没有明确的标注、储存不当等现状,在老师的指导下,学生利用课余时间对实验室标本按系统或局部特点进行重新规划、整理,对相应单元内的每一件标本进行拍照,并对照片中的标本各个部位进行中英文对照标注以及简短的标本解析.通过标本精析可以充分利用现有的教学资源,综合、灵活运用人体标本这种极其重要的直观教具,激发医学生学习兴趣,提高动手能力,为以后的临床实践奠定扎实的基础.

Conjugated polymers have excellent properties and can be used in photothermal therapy (PTT). Nevertheless, the concept to design and optimize the photothermal performance by cooperative non-bonding interactions is still in its infancy. Herein, a series of diketopyrrolopyrrole (DPP) derivatives containing chalcogen and fluorine atoms were synthesized to reveal how intra- and intermolecular interactions affect the therapeutic performance of cancer in vitro and in vivo. The synergistic π-π and FH interactions facilitate fluorine and selenium-substituted DPP-SeF to elevate their photothermal conversion efficiency up to 62% from 32% without fluorine and selenium-substituted DPP-SS, and the half-maximal inhibitory concentration drops to ∼8.36 μg mL-1 for DPP-SeF from 15.14 μg mL-1 for DPP-SS on A549 cells under 808 nm light irradiation. More interestingly, efficient tumor killing ability and magnificent biocompatibility on an animal model of A549 transplanted tumor reassert that DPP-SeF nanoagents have immense potential as photoacoustic/PTT agents. Thus, this work presents an efficient phototherapeutic agent, and meanwhile demonstrates the facile concept of accessing the synergistic effect of non-bonding interactions to promote antitumor efficiency by ingenious molecular engineering.

Background: Aberrant expression of caveolin-1 (CAV-1) is involved in the pathogenesis of hepatocellular carcinoma (HCC); however, the results have been inconsistent due to the small size of sample in the individual study. Methods: We performed a meta-analysis and evaluated the association of CAV-1 protein overexpression and clinicopathological significance by using Review Manager 5.2. Pooled ORs and HR with corresponding CIs were calculated. Results: Nine studies were included in the meta-analysis with 810 HCC and 172 cirrhosis patients. CAV-1 protein overexpression was correlated with the risk of cirrhosis; OR was 3.25, p=0.01. Furthermore, the rate of CAV-1 protein overexpression was significantly higher in HCC with cirrhosis than HCC without cirrhosis, suggesting that the CAV-1 protein overexpression likely initiated carcinogenesis in liver with cirrhosis and subsequently contributed to the progression of HCC. In addition, CAV-1 protein overexpression was strongly associated with poor differentiated HCC and invasion; ORs were 2.61 and 2.71, respectively. CAV-1 protein overexpression was strongly correlated with poor overall survival in patients with HCC; HR was 0.4, p=0.03. Conclusions: In summary, CAV-1 protein overexpression is at risk for liver cirrhosis and HCC derived from cirrhosis, and CAV-1 is also a promising prognostic predictor in HCC.

AIM:To explore the expression profile of some DHRS genes in high-grade serous ovarian cancer (SOVC) and to study their prognostic values.PATIENTS & METHODS:A retrospective bioinformatic analysis was performed using data in the Gene Expression Omnibus, the Human Protein Atlas and the Cancer Genome Atlas-Ovarian Cancer.RESULTS:Increased DHRS12 expression was an independent indicator of poor overall survival (hazard ratio [HR]: 1.265, 95% CI: 1.075-1.488; p = 0.005) and recurrence-free survival (RFS; HR: 2.242, 95%CI: 1.464-3.432; p < 0.001) in patients with high-grade SOVC. DNA deletion was associated with decreased DHRS12 expression, as well as the best overall survival and RFS among the three copy number alteration groups.CONCLUSION:DHRS12 might serve as a valuable prognostic biomarker in high-grade SOVC.

目的 探讨小鼠的血脑屏障(BBB)及血脑脊液屏障(BCSFB)的基本结构及其在阿尔茨海默病(AD)发生、发展过程中结构、功能及及其超微结构的改变.方法 实验用动物采用APPSWE Tg2576鼠,分为APPSWE转基因阳性鼠(模型组)和同窝生野生型小鼠(对照组),每组各20只.饲养16个月后进行全身灌流固定,开颅切取侧脑室室壁及其脉络丛组织.采用免疫荧光及透射电子显微镜技术观察BBB及BCSFB的超微结构,从而观察AD模型脑屏障的改变.结果 AD模型组与对照组相比较,血管密度明显降低;AD小鼠脑屏障正常结构受到损害,主要是脑血管内皮细胞(或脉络丛内皮细胞)之间的连接及其细胞器受损,脉络丛超微结构也出现明显变化,主要表现为细胞间隙增宽,细胞之间的黏附连接等连接结构也有部分碰坏,胞质内出现较多的囊泡状结构等.结论 和正常鼠相比,AD鼠脑屏障受到一定的损害,可能致使脑屏障的转运机制出现相应的改变并影响脑内β-淀粉样蛋白(Aβ)的清除,脑屏障中存在的稳态机制,如其分泌物和受体介导的信号传导也可能出现改变,这些因素可能共同参与了AD的形成和进展.

Cold exposure is an external stress factor that causes skin frostbite as well as a variety of diseases.Estrogen might participate in neuroprotection after cold exposure,but its precise mechanism remains unclear.In this study,mice were exposed to 10°C for 7 days and 0–4°C for 30 days to induce a model of chronic cold exposure.Results showed that oxidative stress-related c-fos and cyclooxygenase 2 expressions,MAP1LC3-labeled autophagic cells,Iba1-labeled activated microglia,and interleukin-1β-positive pyramidal cells were increased in the hippocampal CA1 area.Chronic cold exposure markedly elevated the levels of estrogen in the blood and the estrogen receptor,G protein-coupled receptor 30.These results indicate that neuroimmunoreactivity is involved in chronic cold exposure-induced pathological alterations,including oxidative stress,neuronal autophagy,and neuroimmunoreactivity.Moreover,estrogen exerts a neuroprotective effect on cold exposure.

To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function.

The objective of this study is to understand the impairment of learning and memory in mouse after chronic nitrite exposure. The animal model of nitrite exposure in mouse was created with the daily intubation of nitrite in adult healthy male mice for 3 months. Furthermore, the mouse's learning and memory abilities were tested with Morris water maze, and the expression of Synaptophysin and gamma-Synuclein was visualized with immunocytochemistry and Western blot. Our results showed that nitrite exposure significantly prolonged the escape latency period (ELP) and decreased the values of the frequency across platform (FAP) as well as the accumulative time in target quadrant (ATITQ) compared to control, in dose-dependent manner. In addition, after nitrite exposure, synaptophysin (SYN) positive buttons in the visual cortex was reduced, in contrast the increase of gamma-synuclein positive cells. The results above were supported by Western blot as well. We conclude that nitrite exposure could lead to a decline in mice's learning and memory. The overexpression of gamma-synuclein contributed to the synaptic loss, which is most likely the cause of learning and memory impairment. (C) 2015 Wiley Periodicals, Inc.

对66只雌性且有阴栓的C57BL/6J小鼠(对照组)每日进行生理盐水灌胃处理,待幼仔娩出,统计不孕率.将对照组哺乳后且有阴栓的雌鼠随机平均分配,分别进行每天60 mg/kg(低剂量亚硝酸盐组)和120 mg/kg(高剂量亚硝酸盐组)的亚硝酸钠灌胃处理,待子鼠娩出,统计不孕率(第一轮暴露模型).按此方法,对第一轮暴露哺乳后且有阴栓的雌鼠进行第二轮亚硝酸钠暴露并统计不孕率.收集对照组和高剂量亚硝酸盐两轮暴露组雌鼠的卵巢,采用HE TUNEL试剂盒观察卵泡内颗粒细胞凋亡情况及诱导型一氧化氮合酶(iNOS)表达情况,利用Westernblot蛋白半定量分析法分析Caspase 8、c-fos蛋白在卵巢内的相对表达量.结果显示:亚硝酸盐暴露可致小鼠不孕且具有剂量依赖性(P＜0.05,n=66);亚硝酸盐暴露可诱导机体产生氧化应激反应、可使卵泡内颗粒细胞iNOS表达增加、颗粒细胞凋亡增加(P＜0.01,n=20).以上结果说明,亚硝酸盐有致不孕效应,可能与NO信号通路和氧化应激诱导的颗粒细胞凋亡和排卵抑制有关.

目的 探讨小鼠大脑皮质发育过程中神经细胞、胶质细胞及血管发生之间的关系.方法 应用免疫荧光、5-溴脱氧尿嘧啶核苷(BrdU)和墨汁血管灌注等技术,对胚胎受孕15d(E15)至生后90d(P90)小鼠大脑内神经干细胞、神经前体细胞、神经胶质细胞和血管进行形态学观察.结果 E15左右大脑皮质内开始出现血管网,随着年龄的增长血管分支逐渐增多,血管体密度呈现增长趋势;成年后(P60)血管密度基本稳定.大脑皮质部位小血管走行方向与放射状胶质细胞长突起延伸方向一致,呈平行分布;大量放射状胶质细胞伸出膨大的足板参与血脑屏障的构筑;增殖的神经干细胞主要沿着血管走行方向及放射状胶质细胞长突起延伸方向进行迁移.结论 在大脑皮质发育过程中,神经干细胞不断增殖,并沿着血管走行方向及放射状胶质细胞长突起延伸方向进行迁移.神经细胞、神经胶质细胞参与血管壁的构成,三者之间相互诱导,共同维持血脑屏障的完整与功能调节.

一氧化氮(NO)作为人体内重要的信号转导分子,参与人体许多生理和病理的调节.本文着重从机体短暂产生少量的NO在生理性自稳态中发挥的作用,比如促进血管扩张、抑制血小板聚集、对细胞增殖和凋亡的影响等生理功能及当外源性因素使体内NO浓度增高或受外界刺激引起的NO代谢紊乱时如何导致疾病的发生,对NO的生理学及病理学作用进行研究,以期对人类健康及疾病的预防有一个全新的认识.

This study was performed to investigate the changes of the number, morphology and ultrastructure of the central nervous system of mice during the long-term alcohol exposure. Mice at 60 days in age were used to establish the long-term alcohol exposure model. The structure of the central nervous system, such as nuclear antigen, dendritic spines and synapses, were labeled by the methods of immunocytochemistry and DiI (1,1’- dioctadecyl-3,3,3’,3’-tetramethy lindocarbocyanine perchlorate) scattering. The results showed that prolonged alcohol exposure could promote apoptosis of nerve cells in the central nervous system, and inhibit the proliferation of neural stem cells, which reduced the number of nerve cells in the central nervous system. Long-term ethanol exposure can also lead to a decrease in the density of dendritic spines of neuron, a smaller number of synapses(connections between nerve cells), and some changes in synaptic ultrastructure. The density of nerve cells and their dendritic spines, as well as the changes of synaptic ultrastructure, suggest that the function of nerve cells may be low.

目的 探讨孕期亚硝酸盐暴露对海马损伤的作用.方法 利用C57BL/6J小鼠建立孕期亚硝酸盐暴露模型,分为对照组(生理盐水)、低剂量亚硝酸盐组(60mg/kg)和高剂量亚硝酸盐组(120mg/kg).收集出生当日(P0)、P7、P14及P30各年龄点仔鼠大脑,用于免疫荧光染色、彗星实验、Western blotting蛋白半定量分析,对海马损伤进行研究.结果 不论是亚硝酸盐暴露组还是对照组,仔鼠齿状同增殖的神经干细胞数目均随着年龄的增长逐渐减少;在P0、P7、P14和P30年龄点,暴露组仔鼠增殖的神经干细胞的数量明显比对照组少,且具有剂量依赖性(P＜0.05,n=96).为了鉴别这种抑制作用是否具有选择性,我们对P0仔鼠室管膜下区神经干细胞的增殖情况进行了观察.结果发现,亚硝酸盐暴露组室管膜下区的神经干细胞增殖较对照组也减少,同样具有剂量依赖性(P＜0.05);亚硝酸盐暴露组仔鼠门区炎症损伤细胞和凋亡细胞的数目比对照组多,具有剂量依赖性(P＜0.05);彗星实验结果显示,亚硝酸盐暴露组P0仔鼠海马细胞的彗尾比对照组长,具有剂量依赖性(P＜0.01);与对照组P0仔鼠相比,亚硝酸盐暴露组仔鼠海马组织内Caspase-8和核因子κB(NF-κB)蛋白的表达量较高(P＜0.05).结论 孕期亚硝酸盐暴露可通过抑制神经干细胞增殖,促进细胞损伤和凋亡而对仔鼠海马造成损伤.

Objective To investigate the differentiation of neural stem cells in the subventridular zone( SVZ) and neural migration along the the rostral migratory stream( RMS) into the olfactory bulb( OB),particularly,Reelin's effect on the neural differentiation and migration in RMS. Methods Wild type mice( 50 cases) and reeler mice( 23 cases)from E16( embryonic day 16) to P90( postnatal day 90) were used for Nissl staining,immunofluorescent labeling,ink perfusion and ultrastructure observation to visualize neural stem cells,the radial glial cells and vasulature in neocortex and RMS. The development of RMS in two groups was compared. Results In embryonic days and early postnatal period,vascular niches in the SVZ consisted of neurons,glial cells,neural stem cells and vascular vessel which provided a ideal microenvironment for the differentiation and mturation of neural stem cells. After maturation in the vascular niche,the neural stem cells started to migrate tangentially along RMS toward olfactory bulb with the chain-guidable pattern along both glial and vascular scaffold. After entering in OB,the migrating pattern translated into the radial migration,and these cells differentiated into various neuron in olfactory bulb. In general,RMS's development,neural stem cell differentiation and cell migration in reeler mice were similar to the wild type,howover,the distribution of vasculature in cortex and RMS was disordered,and the migrating cells often concentrated in olfactory bulb densely and scatteredly. Conclusion Niche in subventricular zone is the main sources of neural stem cells,and both vasculature and radial glia and acts as a scaffold for the migration of neural stem cells in RMS. As an important signal for cell migration,Reelin can affect the development of blood vessels and cell migration in RMS. Without Reelin,the cell migration in RMS will be blocked.

Recently, cold‐adaptation medicine has gotten more and more attention because of its specific significance to health care, military activities, sports performance, and so on. Although numerous studies have focused on respiratory, immune, and circulatory systems as well as skin damage upon cold exposure, the impacts on central nervous system are not well understood. This study explores the effects of chronic cold exposure on the murine central nervous system. To establish a chronic cold‐exposure animal model, adult male mice from postnatal days 40–50 (P40–50) were housed at 0–4°C for 20 days. During the study period, estrogen receptors were labeled via immunohistochemistry, the dendritic spines of visual cortical pyramidal cells were labeled with DiI diolistic assay, and synaptic ultrastructure was observed by transmission electron microscopy. The results showed that cold exposure could inhibit neural proliferation significantly, with an increase of G‐protein‐coupled receptor 30 (GPR30) expression. Chronic cold exposure could also induce a decrease in the dendritic spines of pyramidal cells in visual cortex, along with a decrease in the number of synaptic formations. The ultrastructure of synapses after cold exposure was observed. It was found that pre‐ and postsynaptic membranes were fused, with a vague synaptic cleft. Furthermore, neuronal cytoplasmic and organelle swellings were also observed, along with microtubule disintegration. In conclusion, chronic cold exposure can cause structural and functional changes in the mouse central nervous system, possibly by direct participation of estrogen and its receptor, GPR30, in response to chronic cold exposure. © 2014 Wiley Periodicals, Inc.