β-adrenergic modulation of <Emphasis Type="Italic">in vivo</Emphasis> long-term potentiation in area CA1 and its role in spatial learning in rats

Activation of β-adrenoceptors in area CA1 of the hippocampus facilitates in vitro long-term potentiation (LTP) in this region. However, it is unclear if in vivo LTP in area CA1 and hippocampus-dependent learning are subjected to β-adrenergic regulation. To address this question, we investigated the effects of the β-adrenergic agonist L-isoproterenol or antagonist DL-propranolol on in vivo LTP of area CA1 and the spatial learning in Morris water maze. In the presence of L-isoproterenol (through local infusion into area CA1), the theta-pulse stimulation with the parameter of 10 Hz, 150 pulses/train, 1 train, a frequency weakly modifying synaptic strength, induced a robust LTP, and this effect was blocked when DL-propranolol was co-administered. By contrast, the theta-pulse stimulation with the parameter of 5 Hz, 150 pulses/train, 3 trains, a frequency strongly modifying synaptic strength, induced a significantly smaller LTP when DL-propranolol was administered into area CA1. Accordingly, DL-propranolol impaired the spatial learning in the water maze when infused into area CA1 20 min pretraining. Compared with control rats, the DL-propranolol-treated rats showed significantly slower learning in the water maze and subsequently exhibited poor memory retention at 24-h test. These results suggest that β-adrenoceptors in area CA1 are involved in regulating in vivo synaptic plasticity of this area and are important for spatial learning.     

β-adrenergic modulation of in vivo long-term potentiation in area CA1 and its role in spatial learning in rats

The hippocampus plays a key role in declarative learning and memory [1]. Hippocampal long-term potentiation (LTP) is a type of synaptic plasticity that has been widely studied as a syn-aptic mechanism underlying learning and memory[27]. It has been reported that in vitro LTP in area CA1 is subjected to b-adrenergic modulation. For example, the theta-pulse stimulation (510 Hz), a neutral frequency not modifying synaptic strength, can elicit a robust LTP in area CA1 in slice when the b-adr…     

基于序列分析的天蚕素A串连融合表达载体的构建

天蚕素A(Cecropin A,CA)是来源于惜古比天蚕(Hyalophoracecropia)的含有37个氨基酸的抗菌肽,在非极性环境中形成α螺旋型结构,具有抗菌活性强、抗菌谱广等特点。为降低天蚕素A对宿主的毒性及提高其表达丰度和稳定性,在序列分析的基础上设计了3条天蚕素A氨基酸序列,分别为CA19、CA36和CA210。根据大肠杆菌密码子的偏爱性分别合成相应的3对寡核苷酸链,并通过重叠PCR方法合成成熟肽CA。将含有CA19、CA36、CA210和CA1～5个拷贝基因的质粒转化大肠杆菌BL21(DE3)和BLR(DE3)PlysS,成功构建了串连融合表达载体,为下一步的抗菌活性及免疫表位的分析打下基础。     

肺癌患者血清CEA，CA19-9，CA125 及CA153 围手术期动态监测的临床 意义

目的:探讨动态监测肺癌患者围手术期血清CEA、CA19-9、CA125及CA153水平变化的临床意义。方法:随机选取2014年5月至2015年5月收治的肺癌患者58例为研究对象,另选取同期在我院接受体检的健康人群15例为对照组。分别测定肺癌患者手术前及术后1天、1周、1个月、3个月的血清CEA、CA19-9、CA125、CA153水平,并与对照组的上述各血清肿瘤标志物进行比较。结果:肺癌患者术前空腹血清CEA、CA19-9、CA125、CA153水平明显高于对照组,差异具有统计学意义(P0.01)。肺癌患者术后1天、1周、1个月及3个月的血清CEA、CA19-9、CA125、CA153水平明显低于术前,差异具有统计学意义(P0.05)。肺癌患者术后1个月的平均空腹血清CEA、CA19-9、CA125、CA153水平高于术后3个月平均水平,但差异不具有统计学意义(P0.05)。结论:对肺癌患者的血清CEA、CA19-9、CA125、CA153水平进行围手术期动态监测有助于评估手术治疗效果。     

β-adrenergic modulation of in vivo long-term potentiation in area CA1 and its role in spatial learning in rats

Activation of β-adrenoceptors in area CA1 of the hippocampus facilitates in vitro long-term potentiation (LTP) in this region. However, it is unclear if in vivo LTP in area CA1 and hippocampus-dependent learning are subjected to β-adrenergic regulation. To address this question, we investigated the effects of the β-adrenergic agonist L-isoproterenol or antagonist DL-propranolol on in vivo LTP of area CA1 and the spatial learning in Morris water maze. In the presence of L-isoproterenol (through local infusion into area CA1), the theta-pulse stimulation with the parameter of 10 Hz, 150 pulses/train, 1 train, a frequency weakly modifying synaptic strength, induced a robust LTP, and this effect was blocked when DL-propranolol was co-administered. By contrast, the theta-pulse stimulation with the parameter of 5 Hz, 150 pulses/train, 3 trains, a frequency strongly modifying synaptic strength, induced a significantly smaller LTP when DL-propranolol was administered into area CA1. Accordingly, DL-propranolol impaired the spatial learning in the water maze when infused into area CA1 20 min pretraining. Compared with control rats, the DL-propranolol-treated rats showed significantly slower learning in the water maze and subsequently exhibited poor memory retention at 24-h test. These results suggest that β-adrenoceptors in area CA1 are involved in regulating in vivo synaptic plasticity of this area and are important for spatial learning.     

Spatial self-organization in a cyclic resource-species model

Biological communities are remarkable in their ability to form cooperative ensembles that lead to coexistence through various types of niche partitioning, usually intimately tied to spatial structure. This is especially true in microbial settings where differential expression and regulation of genes allows members of a given species to alter their lifestyle so as to fill a functional role within the community. The resulting species interactions can involve feedback, as in the case of some bacterial consortia that participate in the cooperative degradation of a given resource in a succession of steps and in such a way that certain "later" species provide catalytic support for the primary degrader. We seek to capture the essential features of such spatially extended biological systems by introducing a lattice-based stochastic spatial model (interacting particle system) with cyclic local dynamics. Here, a given site progresses through a sequence of resource and species states in a prescribed order. Furthermore, this succession of states (at a site) is assumed to form a cyclic pattern due to a natural feedback mechanism. We explore conditions under which all the species are able to coexist and consider the extent to which this coexistence requires the development of spatio-temporal patterns, including spiral waves. This self-organization, if it occurs, results when synchronization of the dynamics at the microscopic level leads to macroscopic patterns. These patterns result in consumer-driven resource fluctuations that generate a form of spatio-temporal niche partitioning. As with most models of this complexity, we employ a mixture of mathematical analysis and simulations to develop an understanding of the resulting dynamics.     

Carbonic anhydrase inhibitors. Selective inhibition of human tumor-associated isozymes IX and XII and cytosolic isozymes I and II with some substituted-2-mercapto-benzenesulfonamides

A series of 2-mercapto-substituted-benzenesulfonamides has been prepared by a unique two-step procedure starting from the corresponding 2-chloro-substituted benzenesulfonamides. Compounds bearing an unsubstituted mercapto group and the corresponding S-benzoyl derivatives were investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), i.e., the cytosolic, ubiquitous isozymes CA I and II, as well as the transmembrane, tumor associated isozymes CA IX and XII. These derivatives were medium potency hCA I inhibitors (K_Is in the range of 1.5–5.7 μM), two derivatives were strong hCA II inhibitors (K_Is in the range of 15–16 nM), whereas the others showed weak activity. These compounds inhibited hCA IX with inhibition constants in the range 160–1950 nM and hCA XII with inhibition constants in the range 1.2–413 nM. Some of these derivatives showed a certain degree of selectivity for inhibition of the tumor-associated over the cytosolic isoforms, being thus interesting leads for the development of potentially novel applications in the management of hypoxic tumors which overexpress CA IX and XII.     

米非司酮治疗子宫内膜异位症疗效的临床研究

目的:研究米非司酮治疗子宫内膜异位症的疗效及副反应。方法:选择94例卵巢子宫内膜异位症患者,采用随机抽样的方法分为米非司酮组(简称米组)和内美通治疗组(简称内组),米组46例,内组48例。利用t检验和x~2检验。结果:米组有效率为91．42%,内组有效率为43．75%,二者比较,P＞0．05,差别无统计学差异;而副反应米组明显低于内组,体重增加米组为15．00%,内组为43．75%,二者比较,P＜0．01,说明存在统计学差异;谷丙转氨酶(ALT)异常米组为4．40%,内组为25．00%,二者比较,P＜0．05,存在统计学差异。结论:米非司酮治疗卵巢子宫内膜异位症与内美通具有相同的疗效,副反应明显低于内美通。     

红花桑寄生总黄酮提取物诱导淋巴瘤细胞株CA46凋亡及其分子机制研究

研究了一种寄主为夹竹桃的红花桑寄生总黄酮提取物(Nispex)对人Burkitt淋巴瘤细胞株CA46的抗肿瘤作用,探讨了其抗肿瘤作用的分子机制.应用MTT法研究Nispex对CA46细胞增殖的抑制效果,细胞集落培养法观察Nispex对CA46中增殖细胞群的影响.采用AO/EB荧光染色、TUNEL分析、DNA凝胶电泳分析以及AnnexinV流式细胞术检测细胞凋亡,Western blot检测Nispex对CA46细胞中NF-κBp65、Bcl-2、Bax、Caspase-3和PARP等蛋白表达的影响.结果表明,Nispex显著抑制CA46细胞增殖和诱导CA46细胞凋亡,作用48 h的IC50值为1.72μg/mL,细胞凋亡率与药物浓度正相关.Nispex能有效上调CA46细胞Bax、Caspase-3蛋白表达,下调NF-κBp65、Bcl-2、PARP蛋白表达.Nispex诱导CA46细胞凋亡可能是通过对NF-κB信号通路的抑制来实现的.     

Carbonic anhydrase inhibitors. N-Cyanomethylsulfonamides—a new zinc binding group in the design of inhibitors targeting cytosolic and membrane-anchored isoforms

A series of N-cyanomethyl aromatic sulfonamides and bis-sulfonamides was prepared by reaction of arylsulfonyl halides with aminoacetonitrile. The obtained derivatives incorporated various aryl moieties, such as 4-halogeno/alkyl/aryl/nitro-substituted-phenyl, pentafluorophenyl or 2-naphthyl. Moderate inhibitory activity was detected for some compounds against the cytosolic human isoform II of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA II, with inhibition constants of 90, 180 and 560 nM for the 4-nitrophenyl-, 4-iodophenyl- and pentafluorophenyl-N-cyanomethylsulfonamides, respectively. Other derivatives acted as weak inhibitors of isoforms hCA I (K_Is of 720 nM–45 μM), hCA II (K_Is of 1000–9800 nM) and hCA IX (K_Is of 900–10200 nM). Thus, the N-cyanomethylsulfonamide zinc binding group is less effective than the sulfonamide, sulfamate or sulfamide ones for the design of effective CA inhibitors.     

REM sleep-active hypothalamic neurons may contribute to hippocampal social-memory consolidation

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Wistar大鼠海马CA1区、CA3区和齿状回区的解剖分割

目的:在体视显微镜下分割Wistar大鼠海马CA1区、CA3区和齿状回(DG)区。方法:24只健康Wistar大鼠,分组如下:①6只大鼠取脑后硫堇染色,观察海马各区细胞形态;②6只大鼠分离出海马,体视显微镜下观察海马形态并分割CA1区、CA3区和DG区,各区分别切片后硫堇染色;③12只大鼠检测海马各区HSP 70的表达。结果:①大脑冠状切片硫堇染色清晰显示出海马CA1区、CA3区和DG区;②体视显微镜下,在海马腹侧面,沿着CA1区和DG区之间的海马沟可分割开CA1区和DG区,沿着CA3区和DG区之间的裂隙可分割开CA3区和DG区;分割后的海马各区细胞形态结构与整体大脑冠状切片上相对应区域的细胞形态结构一致;③Western blot结果显示:与对照组相比,脑缺血组HSP 70的表达在海马CA3+DG区明显上调、而在CA1无明显变化,这一结果与免疫组织化学结果一致。结论:上述方法可比较明确地分割Wistar大鼠海马CA1区、CA3区和DG区,分割得到的各区组织可用于蛋白质表达的检测。     

The roles of carbonic anhydrases IX and XII in cancer cell adhesion,migration, invasion and metastasis

The main function of carbonic anhydrases (CAs) in cancer cells is the pH regulation through a conversion of H₂O and CO₂ to H⁺ and HCO₃⁻. However, the data of in vitro and in vivo studies have demonstrated that transmembrane isoforms of CA IX and CA XII are involved in various steps of cancer cell migration, invasion and metastasis. According to literature, inhibition of these CAs can affect the expression of multiple proteins. Some scientific groups have reported the possible interactions between CA IX and E-cadherin–catenin system, CA IX and integrins, CA IX, CA XII and ion transporters, which all are highly involved in cell-to-cell adhesion, the formation of membrane protrusions and focal adhesions. Nevertheless, CA IX and CA XII have a high impact on tumour growth and metastases formation. The data discussed in this review are quite recent. It highly support the role of CA IX and CA XII in various cancer metastasis processes through their interactions to other invasion proteins. Nevertheless, all findings show the great potential of these CAs in the context of research and application in clinical use.     

Volatile constituents of four Inula species of Bulgarian origin

In this study the volatile components of four Inula species (Inula germanica L., I. bifrons (L.) L., I. ensifolia L., and I. salicina L.) were analysed by GC-FID/MS. A total of 141 chemical compounds were identified. A distinct volatile chemical profiles with high variation in the type of compounds was observed. Inula germanica was rich in oxygenated monoterpenes (54.7%), with cis-carvyl acetate (20.7%) and 1,8-cineole (14.6%) as main components. Sesquiterpenoids dominated in I. bifrons (60.3%), while the relatively high percentage of fatty acids characterized the other two species I. ensifolia and I. salicina (44.1 and 39.8%, respectively). Principal component analysis (PCA) and cluster analysis (CA) were used to investigate the variations in the volatiles of different Inula species.     

紫杉醇与地西他滨对晚期胃癌患者血清CEA、CA19-9 及CA72-4水平的影响

目的：探讨紫杉醇联合地西他滨对晚期胃癌患者血清癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、糖类抗原72-4(CA72-4)水平 的影响。方法：收集2013 年10 月-2015 年1 月于我院住院治疗的晚期胃癌患者122 例,随机分为实验组和对照组。实验组患者给 予紫杉醇和地西他滨化疗,对照组患者给予紫杉醇和安慰剂化疗。观察并比较两组患者治疗前后卡氏积分、血常规、血尿素氮、肌 酐、转氨酶含量以及血清CA199、CEA及CA724 水平的变化情况。结果：治疗后,两组患者的卡氏积分均较治疗前明显升高,血清 CEA、CA19-9、CA72-4水平均较治疗前显著降低,且实验组的卡氏积分显著高于对照组,血清CEA、CA19-9、CA72-4 水平明显低 于对照组,差异均具有统计学意义（P＜0.05）。治疗前后,两组患者的白细胞、血红蛋白及血小板水平比较均无统计学差异（P＞ 0.05）。结论：紫杉醇联合地西他滨能有效降低晚期胃癌患者血清CEA、CA19-9、CA72-4 水平,并提高患者的生存质量,且安全性 较好。     

Clinical evaluation of the simultaneous determination of CA 15-3, CA 125 and sHER2 in breast cancer

Objective We investigated serum levels of CA 15-3, sHER2 and CA 125, and their usefulness in the detection of metastatic disease in breast cancer patients.

Methods The levels of CA 15-3, sHER2 and CA 125 tumour markers were determined in 60 patients, 40 with localized and 20 with metastatic breast carcinoma. The control group consisted of 10 healthy women.

Results We found that, at the time of diagnosis, serum levels of all three tumour markers were elevated in patients with distant metastases, but of minute importance in the detection of any breast cancer. When the data for the individual markers were combined the overall sensitivity of metastases detection with all three markers improved. In this regard, 90% of patients with distant metastases had an increase in serum level of at least one of tested tumour markers. Similar results were obtained using receiver operating characteristic curve (ROC). Moreover, using ROC we defined cut-off values for metastasis detection for each of the tested markers.

Conclusion Our findings indicate that measurement of CA 15-3 serum values in conjunction with sHER2 and CA 15-3 can increase sensitivity in metastasis detection.     

上皮性卵巢癌患者CT、MRI影像学特征及与血清标志物CEA、CA199、CA125水平的相关性研究

摘要 目的：探讨上皮性卵巢癌患者电子计算机断层扫描（CT）、磁共振成像（MRI）影像学特征及与血清标志物癌胚抗原（CEA）、糖类抗原199（CA199）、糖类抗原125（CA125）水平的相关性。方法：回顾性分析2014年4月-2020年2月于我院83例诊断为上皮性卵巢癌患者的CT、MRI影像学资料,以手术病理结果作为金标准。分析患者的CT、MRI影像学特征,检测患者血清CEA、CA199、CA125水平,评价患者CT、MRI影像学特征与血清CEA、CA199、CA125水平的相关性。结果：上皮性卵巢癌肿瘤横截面最大径为14.2mm-121.7mm,平均（18.6±4.3）mm,上皮性卵巢癌以混杂密度/信号为主,形态不规则,病灶多为囊实性,可见壁结节及分隔改变,增强后可见分隔或壁结节明显强化,可伴有腹水、腹膜转移、淋巴结转移。血清CEA、CA199、CA125水平分别为（66.35±7.52）ng/mL、（183.59±22.62）U/mL、（225.27±25.34）U/mL。上皮性卵巢癌边界清晰、不清晰的血清CA199、CA125水平组间差异有统计学意义（P＜0.05）;上皮性卵巢癌形态圆形/类圆形/椭圆形、分叶状、形态不规则的血清CA199、CA125水平组间差异有统计学意义（P＜0.05）;上皮性卵巢癌患者有壁结节、腹膜转移、淋巴结转移的血清CEA、CA199、CA125水平组间差异有统计学意义（P＜0.05）;其余CT、MRI影像学表现特征组间血清CEA、CA199、CA125水平差异无统计学意义（P＞0.05）。上皮性卵巢癌边界与血清CA125水平呈正相关（P＜0.05）,上皮性卵巢癌形态与血清CA199、CA125水平呈正相关（P＜0.05）,壁结节与血清CA125水平呈正相关（P＜0.05）,腹膜转移、淋巴结转移与血清CEA、CA199、CA125水平呈正相关（P＜0.05）,其余指标之间无明显相关性（P＞0.05）。结论：上皮性卵巢癌CT、MRI影像表现具有特征性,血清CEA、CA199、CA125水平的检测有助于对早期上皮性卵巢癌的诊断以及不同病理类型的判断,CT、MRI影像学特征与血清CEA、CA199、CA125水平具有相关性,可判断疾病的进展及患者预后情况,对指导临床综合治疗及评估患者预后可提供客观依据。     

Clinical evaluation of the simultaneous determination of CA 15-3, CA 125 and sHER2 in breast cancer

Objective We investigated serum levels of CA 15-3, sHER2 and CA 125, and their usefulness in the detection of metastatic disease in breast cancer patients.

Methods The levels of CA 15-3, sHER2 and CA 125 tumour markers were determined in 60 patients, 40 with localized and 20 with metastatic breast carcinoma. The control group consisted of 10 healthy women.

Results We found that, at the time of diagnosis, serum levels of all three tumour markers were elevated in patients with distant metastases, but of minute importance in the detection of any breast cancer. When the data for the individual markers were combined the overall sensitivity of metastases detection with all three markers improved. In this regard, 90% of patients with distant metastases had an increase in serum level of at least one of tested tumour markers. Similar results were obtained using receiver operating characteristic curve (ROC). Moreover, using ROC we defined cut-off values for metastasis detection for each of the tested markers.

Conclusion Our findings indicate that measurement of CA 15-3 serum values in conjunction with sHER2 and CA 15-3 can increase sensitivity in metastasis detection.