突变前后FOXL2基因的生物信息学分析研究

目的 以人类基因组数据库及前期的实验结果为基础,对突变前后FOXL2基因进行生物信息学研究.方法 利用BLAST程序进行FOXL2的基因结构和相似性序列搜索;对FOXL2编码蛋白进行序列结构预测和功能分析.结果 FOXL2定位于3q23,为一单外显子基因,其开放型阅读框架为1134bp,编码376个氨基酸.编码的氨基酸含有特征性的forkhead DNA结合域,为转录因子家族一员,是一跨膜蛋白.突变后的FOXL2在结构和功能上发生了改变：892C＞T突变后蛋白质由376位缩短为218位,丧失了跨膜结构,球状结构变得松散;951 ～ 953delC突变后蛋白质由376位缩短为269位,膜内结构缩短;901～930dup30突变后增加了10个丙氨酸,跨膜的螺旋状结构延长.结论 通过对FOXL2的生物信息学研究发现正常的FOXL2是转录因子家族成员,为～跨膜球状蛋白,通过与DNA相结合而起作用.通过对突变后FOXL2的生物信息学研究发现突变后FOXL2生物学结构与功能的改变,可能是小睑裂综合征的致病原因.     

神经源性异位骨化相关差异基因的筛选及生物信息学分析

目的:基于GEO数据库筛选神经源性异位骨化的差异基因并进行生物信息学分析,寻找疾病相关基因和通道。方法:从GEO数据库中下载关于神经源性异位骨化的基因表达谱芯片,通过R软件的Limma包以调整后的P0.05和|Log2(fold-change)|2作为阈值筛选异位骨化组和健康对照组的差异基因,使用Matascape在线工具对差异基因进行GO富集及KEGG通路富集分析,并构建差异基因蛋白质-蛋白质相互作用关系(PPI)网络,利用Cytohubba和MCODE算法寻找关键基因。结果:共筛选出276个差异基因,其中上调基因150个,下调基因126个,差异表达基因的生物学过程(BP)主要在化学突触传递、跨突触信号的调控、骨化等过程富集;分子功能(MF)主要在细胞外基质结构成分、肝素结合、糖胺聚糖结合富集;细胞成分(CC)主要在胶原三聚体、含胶原蛋白的细胞外基质、细胞外基质富集。KEGG信号通路分析主要富集在补体和凝血级联、IL-17、Wnt、蛋白的消化吸收等通路。PPI网络共鉴别出EGF、GPR18、ADRA2C、CXCL1、C3、CXCL6、ADRB2、PENK、CXCL2、CDH1共10个hub基因和CXCL2、PTH2、EPHB1、HTR2B共4个种子基因。结论:通过对基因芯片的生物信息学分析,发现了可能与神经源性异位骨化相关的基因及分子调控机制。     

儿童急性淋巴细胞白血病6q16.3微卫星DNA缺失及生物信息学分析

目的定位儿童急性淋巴细胞白血病（ALL）杂合性缺失（LOH）的集中区域,探索新的肿瘤抑制基因.方法取6q16.3的15个微卫星标记,用聚合酶链反应-变性凝胶电泳-银染技术对165例ALL患儿等位基因LOH的情况进行生物信息学分析;同时分析其与临床预后因素的相关性.结果至少1个位点的LOH率为32.7%,D6S1709-D6S1028及D6S2160-D6S1580是高频率集中缺失的区域,早期复发患儿的LOH率高于无早期复发患儿;谷氨酸受体6基因（GRIK2）可能为抑癌基因,2个区域存在可能代表新基因的表达序列标签12个.微卫星LOH与白细胞计数、病态细胞数、核型分析、早期复发均有相关性（P值均＜0.05）.结论D6S1709-D6S1028和D6S2160-D6S1580为目前国内外所确定的最精确缺失区,该区域可能存在1个或数个肿瘤抑制基因,6q16.3的LOH的发生与ALL预后有一定关系.     

用基因芯片筛选乳腺癌细胞耐药相关基因

摘要：目的：通过挖掘基因芯片数据,识别可能与乳腺癌细胞耐药相关的基因。 方法：从基因表达数据库（Gene Expression Omnibus,GEO）中下载编号为GSE28784基因芯片数据,分析乳腺癌敏感细胞系MDA-MB-231/S和多西紫杉醇耐药细胞系MDA-MB-231/Doc中基因表达差异,获得差异表达基因,并对这些基因进行生物信息学分析。 结果：得到639个表达差异的基因,与敏感细胞系相比,分别有220和419个基因在耐药细胞系中表达下调或上调;这些基因主要参与调控细胞死亡、凋亡、迁移和免疫效应等过程;表皮生长因子受体（EGFR）、JUN、白介素6（IL-6）、蛋白酪氨酸激酶2（PTK2）和多药耐药蛋白1（ABCB1）等已知与耐药相关的基因可能参与了乳腺癌细胞对多西紫杉醇的耐药。 结论：基因芯片数据的挖掘为进一步研究乳腺癌细胞的耐药机制提供了方向。     

白细胞介素6（IL-6）与肾脏疾病

IL-6的研究始于80年代初，曾被称为B细胞刺激因子-2(Bcell stimulatory factory-2)、B2干扰素、26KDa诱导蛋白和肝细胞刺激因子(Hepatocyte Stimulatory factory)等．通过对这些物质的纯化鉴定和基因结构分析，己证实为同一种蛋白体，现统称为IL-6。     

hβ-NGF基因真核表达载体构建及亚细胞定位

目的构建含EGFP标签的人β-神经生长因子(hβ-NGF)的真核表达载体,观察和分析其在HEK293细胞中的定位,为后续基因转移实验奠定基础。方法PCR扩增hβ-NGF基因编码框,连接到pEGFP-N1载体,将HEK293细胞分为对照组(不转染)、空载组(转染pEGFP-N1质粒)和实验组(转染pEGFP-N1-hβ-NGF质粒),后两组采用脂质体法转染,24h后荧光显微镜下观察EGFP瞬时表达及细胞定位,通过蛋白序列数据库和生物信息学软件进一步分析亚细胞定位。结果经双酶切和测序鉴定,pEGFP-N1-hβ-NGF真核表达载体构建成功。与空载组比较,实验组融合EGFP只少量分布于胞质中(P0.05),不存在于细胞核内。生物信息学分析表明,hβ-NGF基因编码长241个氨基酸的肽链,由信号肽、前导肽和功能肽3段构成,含有2个N-糖基化位点,6个高度保守半胱氨酸残基,可以形成3个二硫键,是可溶、不稳定的分泌型蛋白;亚细胞定位该蛋白主要位于细胞外,部分分布于胞吞内体和高尔基体,以模序二聚体形式发挥生物学功能。结论成功构建了有活性的hβ-NGF真核表达载体,观察到融合蛋白在HEK293真核细胞系分泌表达,其亚细胞分布与生物信息学分析一致。     

精神分裂症患者丝氨酸消旋酶和D构象氨基酸氧化酶的生物信息学与功能分析

目的 D-ser作为一种重要的神经胶质细胞递质,其合成与代谢依赖于丝氨酸消旋酶（SR）和D构象氨基酸氧化酶（DAO）,SR及DAO基因与精神分裂症密切相关,本研究目的为阐明精神分裂症患者SR及DAO结构与功能的关系。 方法 从精神分裂症血液中克隆到SR及DAO基因,对其进行生物信息学分析。 结果 序列分析结果表明,SR及DAO基因分别编码340个和347个氨基酸的多肽,与健康人、猿、猴的同源性在96%以上;预测SR及DAO蛋白质的相对分子质量分别为36.57 KDa和39.47 KDa,理论等电点分别为6.11和6.36。亚细胞定位分析结果发现,SR蛋白主要定位于细胞的线粒体中,DAO蛋白主要定位于线粒体和过氧化物酶体中,提示此两种蛋白在细胞中主要发挥合成与代谢作用。结构与功能分析发现,SR蛋白有1个结构域,DAO蛋白含有2个结构域和一个链接区。 结论 推测SR及DAO在真核细胞的蛋白质合成与代谢等过程中发挥重要功能。       

大规模测序研究CD_(34)~ 造血干/祖细胞基因表达谱

目的　建立大规模测序方法 ,并用于造血干 祖细胞 (HSPC)基因表达谱的初步识别。方法　从脐血中分离CD34 细胞 ,构建cDNA文库 ,对其进行大规模表达序列标签 (EST)测序 ,用生物信息学的方法进行结果分析。结果　在获得的 986 6条EST中 ,有意义序列归并为 2 0 6 0个连续克隆 ,其中10 5 4个为已知基因 ,10 0 6个为至今尚未被公共数据库公布的新基因片段。 10 5 4个已知基因根据功能分为八个大类 :①造血相关的 73个 ;②染色体结构及细胞分裂相关的 91个 ;③细胞信号传导相关的111个 ;④细胞结构 运动相关的 48个 ;⑤细胞和机体防御相关的 41个 ;⑥基因表达 (转录、翻译及加工 )相关的 2 6 5个 ;⑦代谢相关的 192个 ;⑧未分类的 2 33个。结论　获得了HSPC表达的 10 5 4个已知基因和 10 0 6个新基因片段构成的初步基因表达谱 ,为进一步深入研究造血基因表达调控和克隆新基因奠定了基础     

大鼠细胞因子信号转导抑制因子-1基因的多态性及其结构分析

目的 扩增大鼠细胞因子信号转导抑制因子-1(SOCS-1)基因,利用生物信息学方法预测其结构和功能特征,为进一步的实验研究提供理论指导.方法 扩增并测序大鼠的SOCS-1编码区序列,利用生物信息学网站的在线分析工具和Vector NTI suite软件包,识别大鼠SOCS-1基因并预测其编码蛋白质的各种结构特征,根据该基因构建其分子进化树.结果 聚合酶链反应(PCR)扩增获得2个序列不同的SOCS-1基因,BLASTx分析该基因为全长基因,该基因全长639 bp,编码212个氨基酸(aa),具有1个SOCS盒(aa172～aa208),1个Scr同源区2(SH2)结构域(aa80～aa155)和1个核定位序列(aa160～aa174),一级结构含有2个线性B细胞抗原表位,全部位于蛋白的表面,并在空间结构上相距较远.结论 SOCS-1基因具有基因多态性,其保守的SH2区域及SOCS盒与其对信号转导通路抑制作用有关,而其核定位序列可能影响其他核转导因子,B细胞线性表位则在免疫诊断方面有较好的应用前景.     

酒精性脂肪性肝炎差异表达基因的生物信息学分析

目的利用生物信息学方法筛选酒精性脂肪性肝炎(ASH)肝组织与正常肝组织间的差异表达基因,为探索ASH的关键基因和分子机制提供理论依据。方法从基因芯片公共数据库下载ASH基因芯片数据集GSE28619和GSE103580,共包括ASH患者肝组织标本28例,正常肝组织标本7例。使用R软件对芯片数据进行整合并筛选出差异表达基因。采用在线DAVID分析软件对差异表达基因进行基因本体论(GO)富集分析,应用R软件中Clusterprofiler包对差异基因进行KEGG信号途径分析,利用STRING及Cytoscape软件进一步构建蛋白质-蛋白质相互作用(PPI)网络,并利用Cytoscape软件中的CytoHubba插件,综合12种拓扑分析方法筛选出前3个核心基因。结果共筛选出28个差异表达基因,GO富集分析发现,差异表达基因参与了皮质醇反应、Wnt蛋白活性、细胞对细胞外刺激的反应、转录因子活性、转录激活因子活性及RNA聚合酶Ⅱ核心启动子近端区序列特异性结合等功能。KEGG通路分析发现,差异表达基因富集在唯一一个通路——白细胞介素-17(IL-17)信号通路上。PPI分析得到3个核心基因,分别为CCL20、FOS及NR4A2,并且CCL20与FOS均富集在IL-17信号通路上。对PPI网络中的节点进行富集分析发现,其功能主要富集在信号转导上。结论通过生物信息学分析,预测CCL20、FOS及NR4A2可能是介导ASH的核心基因,其中CCL20可能通过作用在IL-17信号通路上,被诱导激活后促进巨噬细胞、中性粒细胞等炎症细胞的募集,从而介导ASH炎症发生。靶向调控IL-17信号通路有望成为ASH治疗的新型疗法。     

Intraperitoneal administration of adipose tissue‐derived stem cells for the rescue of retinal degeneration in a mouse model via indigenous CNTF up‐regulation by IL‐6

As the world's population begins to age, retinal degeneration is an increasing problem, and various treatment modalities are being developed. However, there have been no therapies for degenerative retinal conditions that are not characterized by neovascularization. We investigated whether transplantation of mouse adipose tissue‐derived stem cells (mADSC) into the intraperitoneal space has a rescue effect on NaIO₃‐induced retinal degeneration in mice. In this study, mADSC transplantation recovered visual function and preserved the retinal outer layer structure compared to the control group without any integration of mADSC into the retina. Moreover, endogenous ciliary neurotrophic factor (CNTF) was elevated in the retinas of mADSC‐treated mice. We found that lipopolysaccharide (LPS) or LPS‐stimulated monocyte supernatant induced the secretion of granulocyte colony stimulating factor (GCSF), CD54, CXCL10, interleukin‐6 (IL‐6), and CCL5 from the mADSC by cytokine array. Network inference was conducted to investigate signaling networks related to CNTF regulation. Based on bioinformatics data, the expression of IL‐6 was related to the expression of CNTF. Additionally, intravitreal injection of IL‐6 in rats produced up‐regulation of endogenous CNTF in the retina. mADSC had a rescue effect on retinal degeneration through the up‐regulation of endogenous CNTF by IL‐6. Thus, transplantation of mADSC could be a potential treatment option for retinal degeneration.     

血清降钙素原、超敏C反应蛋白及白细胞介素-6在小儿急性上呼吸道感染中的诊断价值

目的探讨血清降钙素原(PCT)、超敏C反应蛋白(hs-CRP)及白细胞介素-6(IL-6)在小儿急性上呼吸道感染中的诊断价值。方法选取该院收治的急性上呼吸道感染患儿136例作为观察组,并根据患儿实验室诊断结果,将观察组患儿分为细菌感染组与病毒感染组,同时选取同期83例健康儿童作为对照组。对比各组PCT、hs-CRP、IL-6水平,同时比较观察组治疗前后PCT、hs-CRP、IL-6水平,比较PCT、hs-CRP、IL-6的诊断价值。结果细菌感染组PCT、hs-CRP、IL-6水平明显高于对照组,差异有统计学意义(P0.05)。治疗后PCT、hs-CRP、IL-6水平明显低于治疗前,差异有统计学意义(P0.05)。PCR敏感度与特异度相对较高,且阳性与阴性预测率均明显高于其他两项,约登指数也有显著提高,差异有统计学意义(P0.05)。三项联合检测虽然敏感度有所提高,但特异度降低,约登指数下降。结论 PCT、hs-CRP、IL-6对于小儿急性上呼吸道感染均有一定的临床意义,PCT作为判断是否为细菌感染的指标特异度更好,真实度更高,对三项指标的联合检测及综合评价,可显著提高急性上呼吸道感染的敏感度,对于早期病情诊断与预后评估等均具有重要的临床意义。     

腹腔置管灌洗对急性重症胰腺炎患者炎症因子水平的影响

【目的】探讨腹腔置管灌洗对急性重症胰腺炎（SAP）患者炎症因子水平影响。【方法】选择2014年1～12月本院普外科室收治的临床诊断为SAP患者82例,按照随机数法将其患者分为观察组（n＝46）和对照组（n＝36）。观察组给予腹腔置管灌洗合并常规治疗,对照组给予单纯常规治疗。比较两组患者不同时间内毒素、肿瘤坏死因子‐α（TNF‐α）、白细胞介素‐6（IL‐6）、IL‐8和C反应蛋白（CRP）动态变化规律,以及两组患者预后指标的差异。【结果】治疗7d后,观察组和对照组血清内毒素、TNF‐α、IL‐6、IL‐8水平均低于治疗前及治疗2d后,差异均具有统计学意义（均P＜00．5）;对照组治疗4d后,血清IL‐6水平低于治疗后2d;治疗4d、7d后,观察组内毒素、TNF‐α、IL‐6、IL‐8、CRP均明显低于对照组同时间点（均P＜00．5）。观察组ICU停留时间短于对照组,胰腺感染率和器官功能障碍综合征（MODS）发生率均低于对照组,差异均有统计学意义（均P＜00．5）;两组患者均无住院死亡病例。【结论】腹腔置管灌洗可降低SAP患者相关炎症反应因子水平,降低胰腺感染率和多器官功能障碍发生率,改善患者预后。     

Does polycythemia affect interleukin‐6 response pattern in early postnatal period?

Introduction: Neonatal polycythemia may result in increased cytokine production. We aimed to investigate whether polycythemia and partial exchange transfusion (PET) affect interleukin‐6 (IL‐6) response pattern in early neonatal period. Methods: Ninety‐four newborns, 57 with polycythemia (Group 1) and 37 as control group (Group 2) were enrolled in the study. PET was performed at 4–6 hr following birth in the first group. Blood levels of IL‐6 were measured at 2–4 hr following birth; measurements were repeated at 6 and 24 hr after PET in newborns with polycythemia and at similar hours in Group 2. In Group 1, two patients (3.5%) who were diagnosed with proven sepsis excluded from the study. Results: Both initial and the last IL‐6 levels were higher in Group 1 (21.7; 5.5–190 pg/ml and 18.3; 2.7–92.4 pg/ml) than those of the controls (8.4; 0.2–47.8 pg/ml and 8.6; 2.0–21.0 pg/ml) (P=0.001 for both comparisons). In Group 1, IL‐6 levels increased at 6 hr after PET and decreased thereafter. IL‐6 showed the same pattern in the control group. IL‐6 levels were higher than >70pg/ml in two (3.6%), seven (12.7%), and two (3.6%) subjects during three evaluation steps, respectively. Neither clinical nor proven sepsis was subsequently detected in any of these subjects. IL‐6 levels were within the acceptable values in Group 2. Conclusion: IL‐6 levels seem to be high in newborns with polycythemia during the first days of life, although they rarely exceed maximum acceptable levels. The pattern of IL‐6 response might be taken into account to optimize its use in the diagnosis of early‐onset neonatal sepsis. J. Clin. Lab. Anal. 24:340–347, 2010. © 2010 Wiley‐Liss, Inc.     

Interleukin‐6 and lipopolysaccharide‐binding protein in acute appendicitis in children

The aim of the study was to evaluate the diagnostic accuracy of interleukin‐6 (IL‐6) and lipopolysaccharide‐binding protein (LBP) in children with acute appendicitis (AA) and to compare this with the diagnostic accuracy of routinely used C‐reactive protein (CRP) and white blood cell (WBC) count. Eighty‐two consecutive children admitted to our Department because of suspected AA were enrolled in this prospective study and classified into two groups: group 1 (49 children who underwent surgery for AA) and group 2 (33 children with no surgery with diagnosis of non‐specific abdominal pain or sonographic mesenteric lymphadenitis). There were no negative appendectomies during the time of the study. The patients were further classified into three subgroups: subgroup 1A (43 patients with advanced AA), subgroup 2A (11 patients with mesenteric lymphadenitis) and subgroup 2B (10 patients with non‐specific abdominal pain). The perforation rate was 32.7?%. WBC count and serum CRP, IL‐6 and LBP were measured on admission. Area under receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity and predictive values were evaluated. Serum IL‐6 and LBP were significantly higher in group 1 than in group 2. The highest AUC for AA was that for IL‐6 (0.776), followed by WBC count (0.684), CRP (0.637) and LBP (0.635). In conclusion, only IL‐6, determined on admission, showed medium diagnostic accuracy, while other laboratory markers showed low diagnostic accuracy for AA in children. The new laboratory markers therefore do not significantly improve the diagnosis of AA.     

辛伐他汀联合厄贝沙坦对糖尿病肾病患者AOPP、ICAM-1、IL-1β水平的影响

目的探讨辛伐他汀联合厄贝沙坦对糖尿病肾病患者晚期氧化蛋白产物(AOPP)、细胞间黏附分子-1(ICAM-1)、白细胞介素1β(IL-1β)水平的影响。方法于2014年5月至2015年5月选择糖尿病肾病患者60例,以抽签法平均分为观察组和对照组,对照组使用厄贝沙坦治疗,观察组在对照组的基础上加用辛伐他汀。观察两组患者治疗前后血压、血脂、肾功能、AOPP、ICAM-1、IL-1β水平变化情况,并比较疗效。结果治疗后,观察组总胆固醇、三酰甘油、血肌酐、血尿素氮、尿清蛋白排泄率、AOPP、ICAM-1及IL-1β水平均低于对照组(P0.05)。观察组临床疗效总有效率为96.67%,高于对照组(70.00%,P0.05)。结论辛伐他汀联合厄贝沙坦对糖尿病肾病患者疗效显著,可有效降低患者体内AOPP、ICAM-1、IL-1β水平,值得在临床推广应用。     

烧伤早期伴发脓毒症患者血清PCT、hs-CRP和IL-6表达水平及临床意义

目的探讨烧伤早期伴发脓毒症患者血清降钙素原(PCT)、超敏C反应蛋白(hs-CRP)和白细胞介素-6(IL-6)表达水平及临床意义。方法回顾性分析该院收治的206例烧伤早期患者病例资料,将其中伴发脓毒症的61例患者作为研究A组,剩余未伴发脓毒症的145例患者作为研究B组,另选取76例同期在该院进行健康体检的同年龄段健康志愿者作为健康对照组。对3组研究对象血清PCT、hs-CRP和IL-6水平进行对比,并分析不同严重程度脓毒症患者因子水平差异,对比研究A组不同预后亚组间血清因子水平。结果 3组对象血清PCT、hs-CRP和IL-6水平差异均有统计学意义(P0.05),且每两组间比较差异也有统计学意义(P0.05);脓毒症、严重脓毒症和脓毒症休克3个亚组间血清PCT、hs-CRP和IL-6水平差异均有统计学意义(P0.05),且每2个亚组间比较差异也有统计学意义(P0.05);预后良好组血清PCT、hs-CRP和IL-6水平均明显低于预后不良组,差异有统计学意义(P0.05)。结论血清PCT、hs-CRP和IL-6水平在烧伤早期伴发脓毒症患者中水平异常升高,且病情越严重,升高幅度越显著,对预后也有评估价值。     

肝癌血清特异标志物Dickkopf-1核酸适体的筛选及其鉴定

目的筛选和鉴定肝癌血清特异标志物Dickkopf-1核酸适体(Apt)。方法采用配体指数级富集系统进化(SELEX)技术,以DKK1为靶蛋白,羧基化琼脂磁珠为筛选介质,从随机ssDNA文库中筛选出一组能够特异性与其结合的核酸适体。利用生物信息学方法对核酸适体进行序列分析和二级结构预测,表面等离子体共振仪分析测定核酸适体的亲和力。结果经过6轮消减SELEX筛选,次级ssDNA文库与DKK1靶标蛋白的亲和力趋向稳定,将第 6 轮筛选产物经PCR扩增进行高通量测序。表面等离子体共振仪检测结果表明,筛选得到的DKK1核酸适体与DKK1的结合解离常数均在纳摩尔级水平,Apt-5的K_d值最小,亲和力最高,Apt-26和Apt-28核酸适体亲和力相对较弱。二级结构预测分析表明,茎环和茎凸环结构为主要的结构形式。圆二色光谱分析结果显示,3个候选核酸适体（Apt-5, Apt-26, Apt-28）能特异形成G-四链体结构识别DKK1靶标蛋白。结论获得了与DKK1靶标蛋白特异性结合的核酸适体,为后续核酸适体的应用研究以及 DKK1蛋白功能的研究奠定了基础。      

Increased levels of C‐reactive protein and interleukin‐6 in hyperhomocysteinemic subjects

Objective. Elevated plasma homocysteine concentration is considered to be an independent risk factor for cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia are related to vascular disease are unclear. High‐sensitivity C‐reactive protein (CRP), a marker of inflammation, has been reported to be an independent predictor of future myocardial infarction among clinically healthy individuals. Interleukin (IL)‐6 is a regulator of CRP and has a key role in initiation of inflammation. The aim of this study was to investigate whether individuals with increased plasma homocysteine concentrations have altered levels of serum CRP and IL‐6. Material and methods. Serum concentrations of CRP and IL‐6 were measured in 39 individuals with hyperhomocysteinemia and in 39 control subjects matched for gender, age and body mass index (BMI). In addition, the inflammatory effect of IL‐6 on peripheral blood mononuclear cells was measured. Results. Compared to controls, hyperhomocysteinemic subjects have elevated serum levels of CRP and IL‐6 (p?0.001 and p<0.005, respectively). Importantly, this raised level of IL‐6 was also seen in hyperhomocysteinemic individuals without accompanying hypercholesterolemia or cardiovascular disease. IL‐6 increased the release of monocyte chemoattractant protein‐1 from peripheral blood mononuclear cells, with particularly enhancing effects in cells from patients with hyperhomocysteinemia. Conclusions. These data suggest that enhanced inflammation may be associated with homocysteine‐related cardiovascular disease, possibly involving IL‐6‐related mechanisms.     

Gastroprotective effect of esculin on ethanol‐induced gastric lesion in mice

The gastroprotective effect of esculin was investigated in a mouse model of ethanol‐induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose‐dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor‐kappa B (NF‐κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6) in ethanol‐treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF‐κB activation, which subsequently reduces expression of iNOS, TNF‐α, and IL‐6.