重组别藻蓝蛋白(rAPC)抑瘤活性及其对免疫作用的研究(英文)

目的:观察重组别藻蓝蛋白(rAPC)对接种H22肝癌细胞小鼠的抑瘤活性及其免疫作用。方法:昆明小鼠随机分为5组(10只/组),即模型组、rAPC低、中、高剂量组(25,50,100mg/kg·d)、环磷酰胺组(CY对照组)。建立小鼠肝癌H22移植瘤模型,次日除模型组外,其余4组分别以不同剂量的rAPC、CY灌胃,于15d后处死,完整剥离出肿瘤、胸腺、脾脏,准确称重,计算抑瘤率、胸腺指数和脾指数,并采用放免法(RIA)测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平。结果:rAPC低剂量组小鼠H22肿瘤质量增长较模型组缓慢(P<0.05),中、高剂量组较模型组显著缓慢(P<0.01),抑瘤率分别为25.2%、36.7%、43.1%;rAPC各剂量组能升高胸腺指数、脾指数和血清中细胞因子IL-6、TNF-α的水平。结论:rAPC可有效抑制H22肝癌的生长,促进小鼠胸腺和脾脏的生长发育,提高小鼠的免疫功能,从而抑制肿瘤的生长。     

别藻蓝蛋白的聚集态研究

为了研究鱼腥藻PCC7120（Anabaena sp．PCC7120）中别藻蓝蛋白（APC）α和β亚基（α-APC和β-APC）中藻蓝胆素（PCB）与脱辅基蛋白的生物合成,并在蓝藻体外对这两种色素蛋白PCB—ApcA和PCB-ApcB合成时聚集过程进行分析,通过多种组合的质粒在大肠杆菌体内共同表达进行重组。色素蛋白的吸收和荧光光谱以及Zn电泳表明,在大肠杆菌体内同时得到色素蛋白PCB—ApcA和PCB—ApcB,并且体内重组色素蛋白的细胞荧光光谱显示,色素蛋白以三聚体的形式存在,而破碎细胞后所得上清液所显示的光谱特征为单聚体的特征。     

藻蓝蛋白的抑瘤活性及抗氧化作用的研究

目的:观察藻蓝蛋白(phycocyanin,PC)对接种S180肉瘤小鼠的肿瘤生长及抗氧化功能的影响。方法:昆明小鼠随机分为6组(10只/组)。即模型组、PC低、中、高、最高剂量组(25,50,100,200mg/kg·d)、环磷酰胺组(CY对照组)。各组小鼠右前腋窝皮下接种S180肉瘤细胞,第二天除模型组外,其余5组分别以不同剂量的PC灌胃、CY(40mg/kg·d)腹腔注射,15天后处死,完整剥离出肿瘤,称重,计算抑瘤率;测定血浆中SOD活力、MDA含量及红细胞溶血度。结果:1.除PC低剂量组外,中、高、最高剂量组肿瘤生长比模型组显著缓慢(P<0.01),抑瘤率分别为34.8%、56.9%、68.4%、61.9%。2.PC高、最高剂量组可升高小鼠血浆中SOD酶的活力(P<0.05);PC各剂量组均能降低小鼠血浆中MDA的含量,最高剂量组与模型组比较有统计学意义(P<0.05),PC低、中、高剂量组与模型组比较有显著差异(P<0.01)。3.除PC低剂量组外,中、高、最高剂量组均能降低红细胞溶血度(P<0.05),其中高剂量组与模型组比较有显著差异(P<0.01)。结论:PC各剂量组可以抑制小鼠S180肿瘤...     

藻蓝蛋白的最新药理活性及作用机制研究

藻蓝蛋白是一种重要的光合辅助色素,包含一个开链的藻蓝素发色团,首先在螺旋藻中被发现。藻蓝蛋白由于具有抗癌、抗氧化等多种生物活性,成为近年天然海洋药物研究的热点。本文对近几年来有代表性的中英文文献进行分析、归纳,介绍关于藻蓝蛋白的最新药理活性的研究状况及可能的机制,为进一步研究其各种生物学功能提供参考。     

柱孢鱼腥藻的藻蓝蛋白亚基和F_(678)色素蛋白

柱孢鱼腥藻的藻蓝蛋白包含有两个亚基。β亚基具有578nm吸收峰和600nm荧光发射峰,分子量19.80±0.40KD,可表明β亚基仅有一个载色团。α亚基具有578nm和630nm吸收峰及645nm的荧光发射峰,分子量17.35±0.38,α亚基可能有两个载色团。别藻蓝蛋白有635nm和650nm吸收蜂及664nm的荧光发射峰。具藻胆体的类囊体膜从高盐浓度缓冲液移至低盐浓度缓冲液时表现678nm荧光发射峰,可能柱孢鱼腥藻存在的F_(678)色素蛋白相当于GLazer(1975)的别藻蓝蛋白B。     

螺旋藻藻蓝蛋白的稳定性及抗癌活性研究

螺旋藻藻蓝蛋白提取物在pH4.0~8.5、40℃以下和弱光环境中表现稳定,并通过MTT比色法测定其对肝癌细胞SMMC-7721和喉癌细胞HEp-2的生长抑制作用,研究了其抗癌活性。     

藻蓝蛋白复合物对酒精性肝损伤的保护作用

本文对藻蓝蛋白复合物保护化学性肝损伤的功效学进行了研究.以Wistar大鼠建立酒精性肝损伤模型,将藻蓝蛋白复合物分为高、中、低三个剂量组,以联苯双酯作为阳性对照组,灌胃给药42 d,分别测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、血清丙二醛(MDA)、谷胱甘肽(CSH)、肝匀浆丙二醛(MDA)和谷胱甘肽(GSH)的含量,并对肝脏切片进行病理检查.结果表明:藻蓝蛋白复合物对血清ALT、AST具有显著的抑制作用,显著拮抗肝脏MDA的升高,显著提高肝脏GSH-Px含量.出现肝细胞浊肿、脂肪变性、点状坏死的大鼠数目极少.从而表明藻蓝蛋白复合物具有显著的保护酒精性肝损伤的功效.     

熊果酸对糖尿病小鼠肾病的保护作用及机制研究

目的：观察熊果酸（UA）对四氧嘧啶诱导的糖尿病小鼠肾病的影响,并探讨其作用机制。方法：昆明种小鼠一次性尾静脉注射四氧嘧啶（70mg／kg）,72h后将血糖高于13．9mmol／L者视为糖尿病模型。随机分为对照组、模型组和uA组（35mg/kg,i．g．）,连续给药8周。测定血糖,肾脏脏器系数,肾组织中超氧化物歧化酶（SOD）,丙二醛（MDA）,肿瘤坏死因子-α（TNF-α）及白细胞介素-6（IL-6）;HE染色观察肾组织病理变化。结果：模型组血糖、脏器指数升高;肾组织中SOD活力降低,MDA含量明显升高;TNE-α,IL-6表达增多;病理学显示模型组肾脏细胞萎缩,排列不整齐,可见炎症细胞浸润和间质增生,UA组明显改善上述变化。结论：熊果酸对四氧嘧啶致糖尿病小鼠肾脏损伤有明显的改善作用,其机制可能与降血糖,抗氧化作用和抑制炎症因子TNF-α、IL-6有关。     

藻蓝蛋白亚基细胞渗透性及对肿瘤细胞光敏作用的研究

目的:研究藻蓝蛋白亚基对SP2/0、S180、COS7、C6的最佳渗透条件及由其介导的PDT对肿瘤细胞的抑制作用。方法:采用柱层析方法从藻蓝蛋白样品中分离得到藻蓝蛋白亚基,通过荧光显微镜观察其在细胞内的渗透特性,并以He-Ne激光器为激发光源,MTT法检测藻蓝蛋白亚基光敏作用对肿瘤细胞生长的抑制作用。结果:藻蓝蛋白α、α/β亚基在75μg/mL浓度下可以在4 h时充分地进入细胞,并可以在细胞内稳定2 h以上;藻蓝蛋白中的α,β亚基稳定性和作用不相同,β亚基荧光性强但易于降解,由α亚基介导的PDT作用比α/βPDT作用强;100μg/mLα亚基介导的PDT对SP2/0和S180两种悬浮细胞的抑制率可分别达到78.6%和39.8%,强于贴壁细胞C6和COS7的29.2%和17.8%。结论:藻蓝蛋白α亚基在合适的渗透条件下表现出较强的光动力学抗肿瘤效果,且PDT效果与光敏剂浓度、照射剂量及细胞类型相关。     

具尾蓝隐藻(Chroomonas caudata Geitler)研究──Ⅱ.藻蓝蛋白(Phycocyanin)的初步分析

初步分析了具尾蓝隐藻（ChroomonascaudataGeitler）的藻蓝蛋白,其吸收光谱为一双峰曲线,两个吸收峰分别为590nm和640nm。按A．N．Glazer等关于隐藻藻蓝蛋白分型的意见,具尾蓝隐藻的藻蓝蛋白属于Ⅱ型PC－645。     

Anticancer activities of an antimicrobial peptide derivative of Ixosin-B amide

In nature, antimicrobial peptides (AMPs) represent the first line of defense against infection by pathogens; thus, they are generally good candidates for the development of antimicrobial agents. Recently, we reported two potent antimicrobial peptides, KWLRRVWRWWR-amide (MAP-04-03) and KRLRRVWRRWR-amide (MAP-04-04), which were derived from a fragment of Ixosin-B-amide (KSDVRRWRSRY). Since some cationic AMPs exhibited cytotoxic activity against cancer cells, in the current study, we further investigated the anticancer activity of these potent antimicrobial peptides by antiproliferative assays and wound-healing assays, and the effect of peptide on the cytoskeleton alteration and cell morphology were analyzed by confocal microscopy. Results indicated that MAP-04-03 not only exhibited inhibitory effects on the proliferation (IC₅₀ = 61.5 μM) and on the cell migration of MCF-7 breast cancer cells (at a concentration of 5 μM), but also affected the cytoskeleton at the concentration of 25 μM. These results demonstrated that MAP-04-03 can serve as a lead peptide analog for developing potent anticancer agents.     

Effect of honey on mRNA expression of TNF-α, IL-1β and IL-6 following acute toxoplasmosis in mice

This study analyzed the mRNA expression of tumor necrosis factor (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in mice experimentally infected with T. gondii undergoing honey treatment. Thirty male mice were divided in groups: pre-treatment/infected (1), infected/non-treated (2), infected/treated (3), non-infected/treated (4) and control (5). Honey was applied for groups 1, 3, 4 by gavage and the mice in group 1–3 were infected by T. gondii tissue cysts. The parasite load and the level of mRNA expression of the aforementioned cytokines in the brains of mice were assessed by qPCR. The mean number of T. gondii tachyzoite in 1 mg brain tissue was 32, 73 and 59 in groups one, two and three, respectively. The mRNA expression of TNF-α increased in group 1, 2 and 3, about 49.1%, 307.3% and 63.2%, respectively but it was down-regulated by 53% in group 4. The mRNA expression of IL-1β and IL-6 was also up-regulated in all groups except group 2. The mRNA level of TNF-α was reduced by 2.7-fold and 1.18-fold in pre-treated/infected (group 1) and infected/treated (group 3) compared with infected/non-treated (group 2). The mRNA level of IL-1β and IL-6 were increased in these groups. The current study demonstrated that honey can stimulate or suppress the mRNA expression of some pro-inflammatory cytokines in mice brains. Furthermore, honey suppresses the TNF-α mRNA expression in the presence of T. gondii infection but it stimulates the IL-1β and IL-6 mRNA expression. Treatment of the mice with honey reduces parasite multiplication in the brain.     

Synthesis and biological evaluation of 4-styrylcoumarin derivatives as inhibitors of TNF-α and IL-6 with anti-tubercular activity

A series of 4-styrylcoumarin have been synthesized by Knoevenagel condensation between substituted 4-methylcoumarin-3-carbonitrile and different heterocyclic or aromatic aldehydes. 4-Methylcoumarin-3-carbonitrile has been synthesized by the base catalyzed reaction between substituted 2-hydroxyacetophenone and ethyl cyanoacetate. The structures of the newly synthesized compounds were confirmed by ¹H NMR, IR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and anti-tubercular activity. Compounds 6a, 6h and 6j exhibited promising activity against IL-6 with 72-87% inhibition and compound 6v showed potent activity against TNF-α with 73% inhibition at 10 μM concentration. Whereas compounds 6n, 6o, 6r and 6u showed very good anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at <6.25 μM.     

Anticancer and immunomodulatory activities of novel 1,8-naphthyridine derivatives

A number of 1,8-naphthyridine derivatives (22–62) have been synthesized and screened for their in vitro cytotoxicity against eight tumors and two non-tumor cell lines. Halogen substituted 1,8-naphthyridine-3-caboxamide derivatives showed potent activity with compound 47 having IC₅₀ of 0.41 and 0.77 μM on MIAPaCa and K-562 cancer cell lines, respectively while, compound 36 had IC₅₀ of 1.19 μM on PA-1 cancer cell line. However, one of the unsubstituted 1,8-naphthyridine-C-3’-heteroaryl derivative 29 showed potent cytotoxicity with IC₅₀ of 0.41 and 1.4 μM on PA-1 and SW620 cancer cell lines, respectively. These compounds were also evaluated for anti-inflammatory activity as suggested by downregulation of proinflammaotory cytokines.     

血清细胞因子变化在新生儿感染性肺炎中的诊断价值

研究IL-6、TNF-α和IL-2R在肺部感染性肺炎新生儿中的诊断价值。

收集2018年12月至2020年12月在本院妇产科出生新生儿(胎龄34~42周)资料, 根据肺部超声结果, 将新生儿分为病例组和正常组, 检测脐血中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-2受体(IL-2R), 独立样本t检验分析差异性, 多元线性回归分析IL-6、TNF-α及IL-2R与出现肺部感染的相关性, ROC曲线分析IL-6、TNF-α及IL-2R的灵敏度, VITEK-60系统鉴定病原菌。

两组一般资料剖宫产率、性别、出生体质量、胎龄等差异均无统计学意义(P > 0.05);与正常组比较, 病例组脐血炎性标志物IL-6、TNF-a、IL-2R水平均升高(P < 0.01);多元线性回归分析IL-6、TNF-a、IL-2R与新生儿出现肺部感染有关(P < 0.05);ROC曲线分析IL-6(> 155.270 pg/mL)的灵敏度为98.5%, 特异性为85.0%, 约登指数max=0.808;TNF-α(> 16.795 pg/mL)的灵敏度为89.6%, 特异性为86.7%, 约登指数max=0.763;IL-2R(> 603.935 U/mL)的灵敏度为70.8%, 特异性为86.7%, 约登指数max=0.575;病例组检出病原菌143株, 包括127例革兰阴性杆菌(肺炎克雷伯菌构成比最高, 为25.87%)和16例革兰阳性杆菌(表皮葡萄球菌构成比最高, 为2.80%)。

IL-6、TNF-α和IL-2R对肺部感染性肺炎具有识别作用, 在鉴别和预测新生儿出现感染性肺炎具有诊断价值。

     

Changes in central and peripheral inflammatory responses to lipopolysaccharide in ovariectomized female rats

Obesity leads to increases in inflammatory responses in a site-specific manner. Ovariectomized animals, usually used as menopause models, exhibit obesity; however, their inflammatory responses have not been fully examined. In the present study, we investigated whether ovariectomy had site-specific effects on inflammatory responses. First, fever and anorectic responses to systemic injections of lipopolysaccharide (LPS) (500 μg/kg, i.p.) were compared between ovariectomized rats (OVX) and sham-operated female rats (Sham). Inflammatory cytokines at the central and peripheral levels were also compared under saline-injected and LPS-injected conditions. Body weight in OVX was significantly higher than in Sham. The anorectic responses (reduction of body weight and food intake) to LPS were higher in OVX than in Sham. In the hypothalamus, all of the examined cytokine (IL-1β, TNF-α and IL-6) mRNA levels in OVX were higher than in Sham under the LPS-injected condition. On the other hand, in serum and adipose tissue, only IL-6, not IL-1β and TNF-α, levels in OVX were significantly higher than those in Sham under the LPS-injected condition. Second, responses to central (intracerebroventricular) injections of LPS (500 ng) were compared between OVX and Sham. The result was that the fever response in OVX was more evident than in Sham. Finally, responses to systemic injections of LPS (500 μg/kg, i.p.) were compared between OVX (OVX-oil) and OVX with estradiol (E) and progesterone (P) supplementation (OVX-EP). The anorectic responses and hypothalamic cytokine mRNA levels under LPS-injected condition were not different between OVX-oil and OVX-EP. These results indicate that ovariectomy enhances inflammatory responses, especially at the central level compared with the peripheral level. As supplementation of E and P could not attenuate the anorectic and cytokine responses to LPS, the deficiency of gonadal steroids might not be directly involved in the increase of inflammatory responses in OVX.     

腹腔镜与开腹手术对胃癌根治术患者TNF-alpha和IL-6 水平的影响研究

目的:探讨腹腔镜与开腹手术对胃癌根治术患者肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平的影响.方法:选取自2011年3月至2013年5月期间来我院就医并行胃癌根治术的72例胃癌患者作为研究对象.并将所有患者随机平均分成腹腔镜组和传统开腹组各36例.其中,腹腔镜组行腹腔镜辅助下胃癌根治术,传统开腹组行传统开腹胃癌根治术.比较两组手术时间、术中出血量、肛门排气时间及住院时间;比较两组患者术前及术后血清TNF-α和IL-6水平.结果:腹腔镜组术中出血量、肛门排气时间及住院时间均明显低于对照组(P＜0.05)腹腔镜组术后TNF-α和IL-6水平明显低于开腹组(P＜0.05),两组比较有显著性差异(P＜0.05).结论:腹腔镜辅助下胃癌根治术较传统开腹胃癌根治术术后血清TNF-α和IL-6水平低,对机体免疫功能影响较小,可减少患者术后感染机会,值得在临床中推广应用.     

Exercise-induced downregulation of serum interleukin-6 and tumor necrosis factor-alpha in Egyptian handball players

Muscles of candidates work at various grades of intensity during handball exercises according to the pace of exercise. The movement pattern involves large number of contractions, feints, dodges and numerous changes in movements, all of which are highly responsible for changes in trainer's organs, including the immune system. In this study, inflammatory mediators involving interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in serum of 18 Egyptian male handball players, selected from Tanta club handball under 21 year’s old team, were analyzed. The analysis was established on samples collected just before and immediately after intermediate reasonable exercise via enzyme linked immunosorbent assay (ELISA). Moreover, white blood cells (WBCs) count and other hematological markers including hemoglobin %, hematocrit value, and platelet count were assessed. Our results demonstrated a significant decrease in the levels of IL-6 and TNF-α after exercise compared to those before exercise. This was coupled with an increase in WBCs and platelets count. It is also noteworthy that there was a significant positive correlation between serum levels of IL-6 and TNF-α in the study subjects coupled with a significant negative correlation between IL-6 and WBCs after the exercise. Therefore, it is concluded that intermediate reasonable exercises result in decreased levels of IL-6 and TNF-α, which result in decreasing of the inflammation and help in healing and rapid recovery of muscles of the candidates.     

急性高原肺水肿患者血清中VEGF,TNF-α,IL-6及NO的含量变化

目的：检测高原肺水肿患者发生及转归过程中内皮生长因子（VEGF）,肿瘤坏死因子-α（TNF-α）,白介素-6（IL-6）和一氧化氮（NO）的含量变化,探讨高原肺水肿发生发展可能的病理生理机制。方法：收集10例高原肺水肿患者治疗前和转归后的血清样本,采用酶联免疫法和硝酸还原测定VEGF,TNF-α,IL-6和NO的含量。结果：VEGF在高原肺水肿发病时血清的含量为（167.9±26.5）pg/ml,而转归之后其含量显著降低为（53.1±17.0）pg/ml,（P〈0.01）;TNF-α在血清中的含量从发病时的（86.2±24.1）pg/ml减少到转归后的（29.2±6.8）pg/ml,（P〈0.05）,有显著性差异。而IL-6的水平也从发病时的（32.3±16.5）pg/ml变化为转归后的（12.5±8.0）pg/ml,虽然有下降的趋势,但没有统计学差异。而高原肺水肿患者血清中的NO水平从发病时的（33.8±3.3）μmol/L明显的升高到转归后的（74.1±6.2）μmol/L,（P〈0.01）。结论：VEGF,TNF-α,IL-6和NO参与了高原肺水肿的发生和转归过程。     

Cytokines in rats experimentally infected with Trypanosoma evansi

The aim of this study was to measure the levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6) in the serum of rats experimentally infected with Trypanosoma evansi and to correlate these levels with hematological parameters. Initially, 48 rats (group T) were intraperitoneally inoculated with cryopreserved blood containing 1 × 10⁶ trypomastigotes per animal. Twenty-eight animals (group C) were used as negative controls and received 0.2 mL of saline by the same route. The experimental groups were formed according to the time after infection and the degree of parasitemia as follows: four control subgroups (C3, C5, C10 and C20) with seven non-inoculated animals each and four test subgroups (T3, T5, T10 and T20) with 10 animals each inoculated with T. evansi. The blood samples were collected by cardiac puncture at days 3 (C3, T3), 5 (C5, T5), 10 (C10, T10) and 20 (C20, T20) post-infection (PI) to perform the complete blood count and the determination of IFN-γ, TNF-α, IL-1 and IL-6 levels using an ELISA quantitative sandwich. Infected rats showed normocytic normochromic anemia during the experimental period. T. evansi infection in rats caused a serum increase (P < 0.01) of IFN-γ, TNF-α, IL-1 and IL-6 levels at days 3, 5, 10 and 20 PI compared to the controls. The multiple linear regressions showed a reduction of 24% in the hematocrit as a consequence of the increased IFN-γ, TNF-α and IL-1. Therefore, we conclude that the infection caused by T. evansi causes an increase in the pro-inflammatory cytokines. These results suggest a synergism among IL-1, TNF-α and IFN-γ contributing to the development of anemia. This increase is associated with the regulation of immune responses against the parasite.