泥鳅多糖对小鼠脾细胞免疫应答的影响

目的:研究泥鳅多糖对小鼠脾细胞免疫应答的影响.方法:分别给正常小鼠、刀豆蛋白(ConA)或左旋咪唑免疫增强小鼠、环磷酰胺免疫抑制小鼠腹腔注射提取的泥鳅多糖,连续给药7d.用~H-胸苷掺入法测定T淋巴细胞的增殖.用~(51)Cr同位素标记法测定细胞毒T淋巴细胞的细胞毒性和天然杀伤细胞的活性.结果:泥鳅多糖5或10mg·kg~(-1)·d~(-1)可以提高T淋巴细胞的增殖,并增强细胞毒T淋巴细胞的细胞毒性和天然杀伤细胞的活性,还能增强ConA解除环磷酰胺对T淋巴细胞增殖抑制的能力,抑制率从环磷酰胺对照组的51.4％分别降低到18.2％和35.1％.而且,给予小鼠10或20mg·kg~(-1)·d~(-1)的泥鳅多糖,可以恢复环磷酰胺所致的天然杀伤细胞活性降低.结论:泥鳅多糖能增强小鼠脾细胞中T细胞、细胞毒T淋巴细胞和天然杀伤细胞的活性.     

牛膝多糖对T淋巴细胞和天然杀伤细胞功能的影响

牛膝多糖（ＡＢＰ）是从中药牛膝根中分离得到的一种有效成分。ＡＢＰ５０－８００ｍｇ·Ｌ－１在体外增强天然杀伤（ＮＫ）细胞活性和促进伴刀豆球蛋白Ａ（ＣｏｎＡ）诱导的肿瘤坏死因子－β（ＴＮＦ－β）产生；但不能提高ＣｏｎＡ诱导的Ｔ淋已细胞增殖反应和白介素２的产生．ＡＢＰ５０及１００ｍｇ·ｋｇ－１ｉｐ明显提高正常小鼠ＮＫ细胞活性和ＴＮＦ─β生成，增强二硝基氟苯诱导的迟发型超敏反应和对抗环磷酰胺对ＮＫ活性的抑制作用。但对ＣｏｎＡ诱导的Ｔ淋巴细胞增殖反应和白介素２的产生无明显影响。表明ＡＢＰ对Ｔ淋巴细胞功能的影响是有选择性的．ＡＢＰ对ＮＫ细胞的杀伤活性的增强作用是明显的．     

酸性菟丝子多糖的化学特征和免疫活性(英文)

目的:研究从菟丝子(Cuscuta chinensis Lam)中提取分离的酸性纯多糖CHC-1的结构特征及免疫活性.方法:利用化学方法和NMR光谱分析方法对CHC-1的结构特征进行了解析,并研究了CHC-1对小鼠抗体生成以及对淋巴细胞增殖率的影响.结果:CHC-1的分子量大于1.0×10~6.糖组份分析结果显示CHC-1是由Rha,Ara,Gal和GalA组成,比例为:0.8:1.0:1.5:0.3.甲基化结果和~1H,~(13)C NMR分析进一步确定了CHC-1中各残基的连接方式.CHC-10.1 g/L能在体外明显升高T,B细胞的增殖率,CHC-125,50 mg/kg显著增加小鼠的脾重,淋巴细胞的增殖率以及促进抗体生成.结论:CHC-1为一种多分支的杂多糖,并具有免疫增强活性.     

地黄多糖b对正常及S180荷瘤小鼠T淋巴细胞功能的影响

地黄多糖ｂ，在体内与体外实验中能明显提高正常小鼠Ｔ淋巴细胞的增殖反应能力，促进白介素２的分泌，显示了明显的元疫调节活性．在对应于其产生明显抑瘤作用的时相里，能相对改善荷瘤小鼠由于肿瘤生长引起的白介素２分泌功能的下降，以及显著的提高此时细胞毒性Ｔ淋巴细胞（ＣＴＬ）的活力。因此认识到地黄多糖ｂ增强ＣＴＬ对肿瘤细胞的杀伤效应功能是其产生抑瘤作用的一个重要途径。     

丙型肝炎患者外周血B细胞和T细胞及其亚群的研究

目的 了解丙型肝炎患外周血B细胞和T淋巴细胞及其亚群的变化。方法 应用单克隆技术测定38例丙型肝炎患外周血B细胞和T淋巴细胞亚群的水平以35名健康人作对照。结果 丙型肝炎患外周血B细胞数显地高于正常人（P＜0．001）、CD3、CD4、CD4／CD8显低于正常人（P＜0．01,P＜0．001）。结论 丙型肝炎患为一种自身免疫调节异常的疾病。     

急性肾炎患儿治疗前后B细胞和T细胞亚群的检测

目的　探讨急性肾炎患儿治疗前后外周血 B细胞和 T细胞亚群含量。方法　应用单克隆抗体技术测定 30例小儿急性肾炎外周血 B细胞和 T细胞亚群 ,并以 35名健康人作对照。结果　急性肾炎患儿外周血 B细胞数显著地高于正常对照组 (P<0 .0 1) ,CD3、CD4、CD4/CD8显著地低于正常人对照组 (P<0 .0 1或 P<0 .0 0 1)。结论　急性肾炎患儿为一种自身免疫调节异常的疾病。     

石见穿多糖通过调控DSCAM-AS1/miR-129-5p轴抑制oxLDL诱导的血管平滑肌细胞增殖、迁移和侵袭

摘要：目的:探讨石见穿多糖对氧化型低密度脂蛋白（oxLDL）诱导的人主动脉血管平滑肌细胞（HASMCs）增殖、迁移和侵袭的影响及可能机制。方法:体外培养HASMCs,不同剂量(0.25,0.5,1 g·L-1)的石见穿多糖干预oxLDL诱导的HASMCs、或oxLDL诱导转染DSCAM-AS1小干扰RNA的HASMCs、或1 g·L-1的石见穿多糖干预oxLDL诱导的转染DSCAM-AS1过表达载体的HASMCs后,CCK-8法和克隆形成实验检测细胞增殖,划痕实验和Transwell分别检测细胞迁移和侵袭,Western Blot检测细胞中E-cadherin和N-cadherin蛋白表达,RT-qPCR法检测DSCAM-AS1和miR-129-5p表达。双荧光素酶报告基因实验验证DSCAM-AS1和miR-129-5p调控关系。结果:石见穿多糖可降低oxLDL诱导的HASMCs的OD值、克隆形成数、划痕愈合率、侵袭数及N-cadherin蛋白表达降低（P<0.05）,而促进E-cadherin蛋白表达（P<0.05）,且呈剂量依赖性。石见穿多糖可降低oxLDL诱导的HASMCs中DSCAM-AS1表达（P<0.05）,而促进miR-129-5p表达（P<0.05）,DSCAM-AS1靶向结合并负调控miR-129-5p表达。沉默DSCAM-AS1可降低oxLDL诱导的HASMCs的OD值、克隆形成数、划痕愈合率、侵袭数及N-cadherin蛋白表达降低（P<0.05）,而促进E-cadherin蛋白表达（P<0.05）。过表达DSCAM-AS1逆转石见穿多糖对oxLDL诱导的HASMCs增殖、迁移和侵袭的抑制作用。结论:石见穿多糖可抑制oxLDL诱导的HASMCs增殖、迁移和侵袭,其作用机制可能与调控DSCAM-AS1/miR-129-5p轴有关。     

BDNF基因修饰淋巴细胞的蛋白表达及对PC12细胞的增殖和H_2O_2损伤的影响

目的　研究脑源性神经营养因子 (brain derivedneu rotrophicfactor,BDNF)基因修饰淋巴细胞的蛋白表达及对PC12细胞的增殖和H2 O2 损伤的影响。方法　采用Lipofec tAMINE将重组大鼠BDNFcDNA导入PA317细胞 ,获取高滴度的病毒上清转染大鼠淋巴细胞 ,流式细胞仪 (FCM)和免疫组化检测BDNF的表达 ,MTT法检测PC12细胞增殖 ,PI染色流式细胞仪 (FCM)检测PC12细胞凋亡。结果　BDNF基因修饰的大鼠淋巴细胞高表达BDNF蛋白 ,其培养上清可促进PC12细胞增殖并能抑制H2 O2 诱导PC12细胞凋亡。结论　BDNF基因修饰淋巴细胞能高表达和分泌具有生物活性的BDNF。     

肾病综合征患儿激素治疗前后血清TNF含量和外周血B细胞及T细胞亚群的研究

目的 探讨肾病综合征患儿激素治疗前后血清TNF和外周血B细胞及T细胞亚群水平。方法 分别应用放免法和单克隆抗体技术测定31例肾病综合征患儿激素治疗前后血清TNF含量和外周血B细胞和T细胞亚群水平，并以35名正常儿童作对照。结果 肾病综合征患儿治疗前血清TNF、B细胞数水平显地高于正常人（P＜0．001），CD3、CD4、CD4／CD8显低于正常人（P＜0．001）。结论 肾病综合征为一种自身免疫调节异常的疾病。     

灵芝多糖对混合淋巴细胞培养反应中白细胞介素2生成和T细胞亚类的影响(英文)

利用混合淋巴细胞培养反应研究了灵芝多糖的免疫作用机理。结果表明培养12h,灵芝多糖(25,50,100,200μg/ml)可促进白细胞介素2的分泌,且具有剂量依赖关系。培养4d后,可增加总的细胞回收量以及Lyt 2~+和L3T4~+细胞的回收量。灵芝多糖还明显增强细胞毒T细胞的功能,在浓度为200μg/ml时,其杀伤活性增加100％。     

沙蚕(Perinereis aibuhitensis)硫酸多糖的结构表征及抗凝血活性研究

目的 对来源于沙蚕（Perinereis aibuhitensis）的硫酸多糖进行结构表征和抗凝血活性研究。方法 采用两步酶解法从沙蚕中提取多糖;利用强阴离子交换色谱和凝胶渗透色谱对粗多糖进行分离纯化;通过离子色谱法、高效液相色谱法（HPLC）、高效凝胶渗透色谱-多角度激光光散射仪（HPGPC-MALLs）联用技术、硫酸软骨素酶ABC酶法分析、核磁共振氢谱（1H-NMR）等方法,研究纯化多糖的化学组成和结构特征;通过测定APTT、PT和TT评价其体外抗凝血活性。结果 从沙蚕中纯化得到了2种硫酸多糖组分PAE1和PAE2,二者的总糖含量、蛋白含量、硫酸根含量及分子量分别为65.21%、14.31%、0.33%、24.49 kDa和53.08%、11.33%、13.46%、57.39 kDa。PAE1主要由Gal（43.58%）、Glc（32.63%）、GalN（8.71%）、GlcA（7.66%）及少量Fuc（2.77%）组成;PAE2主链为硫酸软骨素C（GlcAβ1→3GalNAc6S）,支链主要由Fuc（35.33%）、Gal（20.9%）和Glc（8.98%）构成。PAE1和PAE2均可明显延长APTT和PT。结论 首次从沙蚕中提取、分离得到2种硫酸多糖,其中PAE2是1种含有Fuc、Gal与Glc支链并具有明显的体外抗凝血活性的结构新颖的类硫酸软骨素,该发现为沙蚕硫酸多糖的开发提供了依据。     

艾叶多糖提取、分离纯化及生物活性研究进展

艾叶为中医常用药材,含有挥发油、酚酸、黄酮和多糖等多种活性成分,其中多糖具有抗氧化、免疫调节、抗肿瘤、降血糖、保肝、调节肠道微生态系统等药用和保健功能,已成为近年的研究热点。本文通过对近十年艾叶多糖的提取、分离纯化以及药理活性等相关研究进行系统性整理、归纳与总结,为艾叶多糖的进一步研究与开发提供数据支持与理论参考。     

Novel,potent calmodulin antagonists derived from an all‐d hexapeptide combinatorial library that inhibit in vivo cell proliferation: activity and structural characterization

Abstract: Calmodulin is known to bind to various amphipathic helical peptide sequences, and the calmodulin–peptide binding surface has been shown to be remarkably tolerant sterically. d ‐Amino acid peptides, therefore, represent potential non‐hydrolysable intracellular antagonists of calmodulin. In the present study, synthetic combinatorial libraries have been used to develop novel d ‐amino acid hexapeptide antagonists to calmodulin‐regulated phosphodiesterase activity. Five hexapeptides were identified from a library containing over 52 million sequences. These peptides inhibited cell proliferation both in cell culture using normal rat kidney cells and by injection via the femoral vein following partial hepatectomy of rat liver cells. These hexapeptides showed no toxic effect on the cells. Despite their short length, the identified hexapeptides appear to adopt a partial helical conformation similar to other known calmodulin‐binding peptides, as shown by CD spectroscopy in the presence of calmodulin and NMR spectroscopy in DMSO. The present peptides are the shortest peptide calmodulin antagonists reported to date showing potential in vivo activity.     

Identification and analytical characterization of six synthetic cannabinoids NNL‐3, 5F–NPB‐22‐7N, 5F–AKB‐48‐7N, 5F–EDMB‐PINACA,EMB‐FUBINACA,and EG‐018

Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances phenomenon. The number of synthetic cannabinoids, the chemical diversity, and the speed of emergence make this group of compounds particularly challenging in terms of detection, monitoring, and responding. Three indazole 7N positional isomer synthetic cannabinoids, two ethyl 2‐amino‐3‐methylbutanoate‐type synthetic cannabinoids, and one 9H –carbazole substituted synthetic cannabinoid were identified in seized materials. These six synthetic cannabinoid derivatives included: 1H –benzo[d ] [1,2,3]triazol‐1‐yl 1‐(5‐fluoropentyl)‐1H –pyrrolo[2,3‐b ]pyridine‐3‐carboxylate (NNL‐3, 1 ), quinolin‐8‐yl 1‐(5‐fluoropentyl)‐1H –pyrrolo[2,3‐b ]pyridine‐3‐carboxylate (5F–NPB‐22‐7N , 2 ), N ‐((1 s,3 s)‐adamantan‐1‐yl)‐1‐(5‐fluoropentyl)‐1H –pyrrolo[2,3‐b ]pyridine‐3‐carboxamide (5F–AKB‐48‐7N , 3 ), ethyl 2‐(1‐(5‐fluoropentyl)‐1H –indazole‐3‐carboxamido)‐3,3‐dimethylbutanoate (5F–EDMB‐PINACA, 4 ), ethyl 2‐(1‐(4‐fluorobenzyl)‐1H –indazole‐3‐carboxamido)‐3‐methylbutanoate (EMB‐FUBINACA, 5 ), and naphthalen‐1‐yl(9‐pentyl‐9H ‐carbazol‐3‐yl)methanone (EG‐018, 6 ). The identification was based on ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry (UHPLC‐QTOF‐MS), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance spectroscopy (NMR). The analytical characterization of these six synthetic cannabinoids was described, so as to assist forensic laboratories in identifying these compounds or other substances with similar structure in their case work. To our knowledge, no analytical data about the compounds 1 – 5 have appeared until now, making this the first report on these compounds. The GC–MS data of 6 has been reported, but this study added the LC–MS, NMR, and Fourier transform infrared (FTIR), data to render the analytical data collection process more complete. Copyright © 2017 John Wiley & Sons, Ltd.     

Structures of neuropeptide γ from goldfish and mammalian neuropeptide γ, as determined by 1H NMR spectroscopy

Abstract: Neuropeptide γ belongs to tachykinin families which have a common C‐terminal amino acid sequence (Phe‐X‐Leu‐Met‐NH₂) and which induce various biological responses including salivation, hypotension, and contraction of gastrointestinal, respiratory, and urinary smooth muscle. In the present study, we present the solution structures of neuropeptide γ (NPγ) from gold fish (G‐NPγ) and mammalian NPγ (M‐NPγ), as determined by nuclear magnetic resonance (NMR) spectroscopy in 50% trifluoroethanol (TFE)/water (1 : 1, v/v) solution and 200 mm sodium dodecyl sulfate (SDS) micelles. In aqueous TFE solution, G‐NPγ has a α‐helical conformation in the region of His¹²–Met²¹ and a short helix in the N‐terminal region, and has a β‐turn from Arg⁹ to Arg¹¹ in between. In aqueous TFE solution, M‐NPγ also has α‐helical conformations both in the C‐terminal region and the N‐terminal region and a β‐turn from His⁹ to Arg¹¹ in between. In SDS micelle, the structure of G‐NPγ contains a stable α‐helix from His¹² to Met²¹ and a β‐turn from Arg⁹ to Arg¹¹, while M‐NPγ has a short helix from Ser¹⁶ to Met²¹. The region from His¹² to Met²¹ corresponds to the amino acid sequence of neurokinin A. Neuropeptide γ may act as a precursor of neurokinin A and the post‐translational processing of this peptide involves the enzymatic attack of the basic β‐turn region from residue 9 to residue 11 in the middle. From our relaxation study, it could be suggested that in fish system G‐NPγ induces the biological actions corresponding to those of substance P in mammalian system. The structures of G‐NPγ and M‐NPγ contain α‐helical structures at the C‐terminus and this helix seems to promote the affinity for NK₁ and/or NK₂ receptor.     

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

Cancer remains the topmost disorder of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.     

Peptides from chiral Cα,α-disubstituted glycines Synthesis and characterization,conformational energy computations and solution conformational analysis of Cα-methyl,Cα-isopropylglycine [(αMe)Val] derivatives and model peptides*

Conformational energy computations on Ac-l -(αMe)Val-NHMe indicate that turns and right-handed helical structures are particularly stable conformations for this chiral Cα-methyl, Cα-alkylglycyl residue. We have synthesized and characterized a variety of l -(αMe)Val derivatives and peptides (to the pentamer level). The results of the solution conformational analysis, performed using infrared absorption, ¹H nuclear magnetic resonance, and circular dichroism, are in general agreement with those obtained from the theoretical investigation, in the sense that the l -(αMe)Val residue turns out to be a strong β-turn and right-handed helix former. A comparison is also made with the conclusions extracted from published work on peptides rich in other Cα-methyl, Cα-alkylglycyl residues.     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.