L型钙流和反向钠-钙交换在豚鼠心室肌细胞兴奋-收缩偶联中的作用

目的 :比较和探讨L型钙流 [ICa(L) ]和反向钠—钙交换 (NCX)在触发豚鼠心室肌细胞兴奋—收缩偶联中的作用。方法 :以分离的豚鼠单个心室肌细胞为对象 ,采用膜片钳和单细胞收缩测量技术 ,给予 35℃的各种含药物细胞外液快速灌流 ,同时记录ICa(L) 和细胞收缩。结果 :①在 +10mV的钳制电压 ,使用硝苯地平 (Nif) 10～ 10 0 μmol/L和Nif 30 μmol/L +Cd2 +30 μmol/L ,阻滞ICa(L) 越多 ,细胞收缩被阻滞得越多 ,呈线性相关。②在 +5 0mV的钳制电压 ,Nif 10 0 μmol/L以及Nif 30 μmol/L +Cd2 +3 0 μmol/L仅能抑制部分细胞收缩 ,但剩余的细胞收缩起始时间明显延迟 ,且能被 5mmol/LNi2 +所阻滞。③在 +10 0mV的钳制电压 ,细胞收缩起始时间较 +5 0mV明显延迟 ,且不能被Nif 10 0 μmol/L和Nif 30 μmol/L +Cd2 +30 μmol/L所阻滞。结论 :在生理条件下 ,ICa(L) 是触发心室肌细胞兴奋—收缩偶联的主要途径 ,但在膜电位 >+5 0mV时 ,反向NCX也参与兴奋—收缩偶联。     

氨甲酰胆碱通过M2胆碱能受体对大鼠心肌细胞发挥正性肌力作用

为研究氨甲酰胆碱（carbachol,CCh）对大鼠心肌细胞的正性肌力作用机制,利用电压钳方法观察CCh对急性分离的单个大鼠心肌细胞L-型钙电流（足扎）和钠,钙交换电流（INa/Ca）的影响。细胞负载Fura-2／AM后,用离子成像系统测定场刺激下单个大鼠心肌细胞的钙瞬变和细胞缩短。结果表明,100ILmol／LCCh使正向INa/Ca从（1．18±0．57）pA／pF增加到（1．65±0．52）pA/pF（P〈O．01）,反向,INa/Ca从（1．11±0．49）pA/pF增加到（1．53±0．52）pA/pF（P〈O．01）,但不影响ICa,L。阿托品（非选择性M胆碱受体拮抗剂）和methoctramine（选择性M2胆碱受体拮抗剂）可阻断这种增加作用。100μmol／LCCh使钙瞬变从对照组的203．8±50．0增加到234．8±64.3,使细胞缩短从对照组的（3．00±0．67）μm增加到（3．55±1．21）μm。KB-R7943（选择性反向INa/Ca抑制剂）不影响钙瞬变和细胞缩短的基础水平,却完全阻断CCh引起的钙瞬变和细胞缩短的增加。尼卡地平（ICa,L抑制剂）抑制钙瞬变和细胞缩短。CCh在尼卡地平存在下仍可增加钙瞬变和细胞缩短值,提示其正性肌力作用是通过刺激钠,钙交换实现的。CCh不改变钙敏感性。阿托品和methoctramine阻断CCh的这种激动作用,说明CCh的正性肌力作用是通过M2受体实现的。以上结果提示,CCh对大鼠心肌细胞有正性肌力作用,这种作用是通过激动反向钠／钙交换实现,由M2受体介导。     

白藜芦醇降低大鼠心室肌细胞内游离钙浓度

实验旨在研究白藜芦醇(resveratrol)对大鼠心室肌细胞内钙浓度(intracellular calcium concentratoin,[Ca2+]i)的影响.应用激光共聚焦显微镜技术记录心室肌细胞内的钙荧光强度.结果表明在正常台氏液和无钙台氏液中,白藜芦醇(15～60μmol/L)呈浓度依赖性地降低[Ca2+]i.蛋白酪氨酸磷酸酶抑制剂正钒酸钠(sodium orthovanadate,1.0 mmol/L)和L型Ca2+通道激动剂Bay K8644(10 μmol/L)可部分抑制正常台氏液中白藜芦醇的效应.但NO合酶阻断剂L-NAME(1.0 mmol/L)对白藜芦醇的作用无影响.白藜芦醇也能明显抑制无钙台氏液中由低浓度ryanodine(1.0 nmol/L)引起的[Ca2+]i增加.当细胞外液钙浓度由1 mmol/L增加到10 mmol/L而诱发心室肌细胞钙超载时,部分心室肌细胞产生可传播的钙波,白藜芦醇(60 μmol/L)可降低钙波的传播速度和持续时间,最终阻断钙波.结果提示,白藜芦醇能够降低心室肌细胞内游离钙浓度,此作用可能与其抑制电压依赖性Ca2+通道、酩氨酸激酶和肌浆网内钙释放有关.     

可视化动缘探测系统检测心肌细胞舒缩功能

目的:分离成年大鼠心室肌细胞,利用可视化动缘探测系统检测其收缩/舒张功能.方法:常规酶解法分离制备钙耐受心肌细胞;用Ca2 荧光探剂fura-2/AM(0.5μmol/L)负载心肌细胞30 min(25℃)后,以含氧台氏液灌流并予电场刺激(0.5 Hz,5 ms),采用动缘探测系统检测心肌细胞收缩/舒张功能及细胞内荧光信号变化.结果:可视化动缘探测系统可实时同步观察和记录心肌细胞机械功能和细胞内钙瞬变变化,并可计算得到细胞收缩/舒张和钙瞬变的变化幅度、时程及速率等一系列指标,从而直接反映细胞水平的心肌功能改变.结论:可视化动缘探测系统为人们提供了一个在单心肌细胞水平探讨心肌肌源性功能及其改变的新方法,是当今心血管研究的一项重要技术.     

白细胞介素-2对大鼠心肌收缩功能的影响涉及一氧化氮机制

为深入研究细胞因子白细胞介素-2(interleukin-2,IL-2)对心肌收缩功能的影响及其可能机制,本实验采用酶解分离成年大鼠心室肌细胞模型,用视频跟踪计算机系统记录测定单个心室肌细胞收缩反应并用双波长荧光系统检测细胞[Ca2+]i.心肌细胞收缩参数包括最大收缩幅度(dL)、细胞最大收缩速度(+dL/dtmax)、细胞最大舒张速度(-dL/dtmax)和舒张末期细胞长度.结果显示,IL-2(2-1000U/ml)浓度依赖性地抑制心肌细胞dL、±dL/dtmax和舒张末期细胞长度;用一氧化氮(ni-tric oxide,NO)合酶抑制剂L-NAME(100mmol/L)和可溶性鸟苷酸环化酶(sGC)抑制剂ODQ(10mmol/L)可减弱IL-2对心肌细胞收缩的抑制作用,iNOS抑制剂Aminoguanidine(100mmol/L)对IL-2的作用则无明显影响.200 U/ml的IL-2可降低单个心室肌细胞电刺激诱导的钙瞬变幅度;ODQ(10mmol/L)可明显抑制IL-2对心肌细胞钙瞬变的作用.以上结果提示IL-2对大鼠心肌细胞收缩功能具有直接抑制作用,其机制可能通过刺激NOS活性,增加NO的生成,激活可溶性鸟苷酸环化酶(sGC)从而导致细胞内Ca2+含量降低所致.     

氨甲酰胆碱通过M2毒蕈碱受体增加豚鼠心肌细胞钠钙交换电流

本文旨在研究氨甲酰胆碱(carbachol, CCh)对豚鼠心肌的正性变力性机制。用Axon200A膜片钳放大器观察CCh 对电压钳制下的豚鼠心肌细胞L-型钙电流(ICa)和钠钙交换电流(INa/Ca)的效应。结果表明, CCh(100 μmol/L)分别使正向INa/Ca从对照组的(1.2 ± 0.1) pA/pF 增加到(2.0 ± 0.3) pA/pF,使反向 INa/Ca 从对照组的(1.3 ± 0.5) pA/pF 增加到(2.1 ± 0.8) pA/pF (P<0.01)。CCh对ICa无影响。CCh 对INa/Ca的激动作用可被阿托品和methoctramine所阻断。以上结果提示, CCh 对豚鼠心脏的正性变力作用是通过激动了钠钙交换,而且是 M2 毒蕈碱受体所介导的。     

胍丁胺对大鼠心室肌细胞内游离钙浓度的影响

本研究旨在观察胍丁胺 (agmatine ,Agm)对分离大鼠心室肌细胞内游离钙浓度 ( [Ca2 +]i)的影响。用酶解方法分离大鼠心室肌细胞 ,用Fluo 3 AM负载 ,然后用激光共聚焦法测定单个心室肌细胞 [Ca2 +]i 的荧光强度 (fluorescenceintensity ,FI) ,结果以FI或相对荧光强度 (F/F0 % )表示。实验结果表明 ,在正常台氏液 (含钙 1 0mmol/L)和无钙台氏液中 ,单个大鼠心室肌细胞的荧光密度分别为 12 8 8± 13 8和 119 6± 13 6,两者无差异。Agm 0 1、1和 10mmol/L浓度依赖性地显著降低细胞的钙浓度 ;在正常台氏液中加入EGTA 3mmol/L ,Agm同样降低细胞的钙浓度。KCl 60mmol/L ,PE 3 0 μmol/L ,和Bay K 864 410 μmol/L均升高心室肌细胞的[Ca2 +]i。Agm同样降低高浓度KCl、Bay K 864 4和PE诱发的心室肌细胞 [Ca2 +]i 升高。当细胞外液钙浓度由 1mmol/L增加到 10mmol/L时 ,诱发心室肌细胞钙超载 ,同时部分心室肌细胞产生可传播的钙波 (Ca2 +wave) ,Agm 1mmol/L降低钙波的传播速度和持续时间 ,最终阻断钙波。以上结果提示 ,Agm对心室肌细胞的胞浆[Ca2 +]i具有抑制作用 ,此作用通过阻断电压依赖性钙通道而实现 ;并可能与抑制大鼠心室肌细胞内钙释放有关     

DMA增加正常大鼠心肌细胞钙瞬变和收缩

实验观察了钠氢交换或钠钙交换抑制剂 5 (N ,N 二甲基 )氨氯吡咪 (DMA)对正常和心肌肥厚大鼠分离心室肌细胞钙瞬变和细胞收缩的影响。通过负载荧光染料Fura 2 /Am ,应用离子影像分析系统 (IonImagingSystem)同步测定离体大鼠心肌细胞钙瞬变和细胞长度。结果表明 :DMA 10 μmol/L分别使钙瞬变和细胞缩短从对照组的 2 0 9.6 0± 5 4.96和 3.0 7± 0 .97μm增加到 2 38.5 0± 80 .41和 4.0 7± 1.0 2 μm (P <0 .0 5 ,n =7)。应用特异性反向钠钙交换阻断剂KB R7943可完全阻断DMA的激动作用。DMA还可使尼卡地平抑制L 型钙通道后的钙瞬变和细胞收缩增加。在肥厚心肌细胞 ,DMA表现出相同的药理作用 ,但对钙瞬变和细胞缩短的刺激作用更强。结果表明 :DMA可通过反向钠钙交换途径增加正常和肥厚大鼠心肌细胞钙瞬变和细胞收缩 ,且对肥厚心肌细胞的影响比对正常心肌细胞大。     

血管紧张素Ⅱ对模拟缺血心室肌细胞L-型钙通道的影响

实验研究了血管紧张素II（AngⅡ)对模拟缺血心室肌细胞L－型钙离子通道的作用,用胶原酶酶解法急性分离豚鼠心室肌细胞,以全细胞膜片钳方法记录心室肌细胞的L－型钙电流（ICa L.)。采用低氧,无糖,高乳酸和酸中毒综合方式模拟缺血液灌流,造成心室肌细胞的模拟缺血,并在缺血的基础上继续用含100mmol/A AngⅡ灌流细胞,观察AngⅡ对模拟缺血心室肌细胞钙离子通道的影响,实验结果显示,模拟缺血时ICa.L峰值电流明显减小,最大激活电压为0mV,AngⅡ能抵抗模拟缺血对ICa,L的抑制效应,使ICa,L峰值电流增大,并使最大激活电压左移至－10mV。     

腺苷抗豚鼠室性心律失常的电生理研究

实验用全细胞膜片钳技术在单个豚鼠心室肌细胞上研究了腺苷 (Ado)对正常及异丙肾上腺素 (Iso)致豚鼠心室肌细胞动作电位、迟后除极 (DAD)、L 型钙电流 (ICa.L)和短暂内向电流 (Iti)的作用。结果表明 :(1)Ado在2 0～ 10 0 μmol/L时对豚鼠心室肌细胞动作电位和ICa .L无明显直接作用 ,但却可明显降低Iso所致的动作电位时程(APD)延长和ICa .L峰值增大 ,Iso (10nmol/L)使细胞APD50 从 3 40± 2 1ms延长到 486± 2 8ms (P <0 0 1) ,APD90从 3 61± 17ms延长至 5 0 1± 2 9ms (P <0 0 1) ;ICa .L峰值从 - 6 5 3± 1 4pA/pF增大到 - 18 2 8± 2 4pA/pF (P <0 0 1) ,电流电压曲线明显左移和下移 ;Ado (5 0 μmol/L)使APD50 和APD90 降至 40 3± 19ms和 419± 2 6ms ,但并不影响动作电位其它参数 ,使ICa.L峰值降低至 - 10 2± 1 5pA/pF (P <0 0 1)。 (2 )Iso (3 0nmol/L)可诱发心室肌细胞产生DADs,其发生率为 10 0 % ;Ado (5 0 μmol/L)可完全抑制Iso引发DADs;细胞经 - 40～ +2 0mV、时程 2s的除极电压 ,Iso (3 0nmol/L)诱导出Iti,其发生率为 10 0 % ;Ado (5 0 μmol/L)可明显抑制Iso致Iti的发生 ,其发生率降为 14 3 %。研究结果提示 ,Ado对豚鼠心室肌细胞动作电位和ICa.L无明显直接作用 ,但却可显著降低Is     

铜、镉对三种豆科植物生长及氮磷钾含量的影响

为了解豆科植物在Cu、Cd单一污染土壤中的生长状况及对土壤养分的吸收利用特点,采用盆栽实验研究了Cu~(2+)、Cd~(2+)单一污染下紫花苜蓿、红三叶、沙打旺3种豆科植物的株高、根长、生物量和叶、茎部N、P、K、Cu和Cd含量的变化情况.Cu~(2+)、Cd~(2+)处理浓度分别为:0、400、800、1200 mg·kg~(-1)和0、1、10、20 mg·kg~(-1).结果表明,3种豆科植物对Cu和Cd均有较强的吸收能力,除红三叶叶片中Cu含量外,3种豆科植物根、茎、叶中Cd和Cu的含量均与土壤中重金属添加量呈显著正相关.3种豆科植物在严重Cd~(2+)污染的土壤中均能正常生长.在Cu~(2+)添加量≤1200 mg·kg~(-1)时,红三叶能正常生长,而紫花苜蓿的生长则受到显著抑制作用,沙打旺在Cu~(2+)添加量≥800 mg·kg~(-1)时生长受到抑制.土壤Cu~(2+)添加量≤1200 mg·kg~(-1)时,能促进紫花苜蓿对N、P、K的吸收;Cu~(2+)添加量≤800 mg·kg~(-1)时,对红三叶N、P、K含量没有明显影响;Cu~(2+)添加量≤400 mg·kg~(-1)时,可提高沙打旺中N、P、K含量,但当Cu~(2+)添加量≥800 mg·kg~(-1)时则显著降低.土壤Cd~(2+)添加量≤20 mg·kg~(-1)时,对紫花苜蓿和红三叶茎叶以及沙打旺茎部的N、P、K含量有促进作用,但对沙打旺叶片的N、P、K含量起抑制作用.总体来看,3种豆科植物对Cu~(2+)和Cd~(2+)均有一定的耐性,红三叶对Cu~(2+)的耐性较好,紫花苜蓿对Cd~(2+)的耐性较好.

Abstract：

Aimed to understand the growth status and nutrient uptake of leguminous plants under soil copper-or cadmium contamination, a pot experiment with Medicago sativa, Trifolium pre-tense, and Astragalus adsurgens was conducted, with their plant height, root length, plant bio-mass, and N, P, K, Cu and Cd contents in leaf and stem measured. The application amounts of Cu~(2+) and Cd~(2+) were 0,400, 800, and 1200 mg·kg~(-1), and 0, 1, 10, and 20 mg·kg~(-1), re-spectively. All the test three leguminous plants had strong capability of absorbing Cu and Cd.The Cu and Cd contents in their roots, stems, and leaves, except the Cu content in T. Pratease leaf, were significantly positively correlated with the application amounts of Cu~(2+) and Cd~(2+). Un-der the application of Cd~(2+), all the three leguminous plants grew normally. When the application amount of Cu~(2+) was≤1200 mg·kgM-1, T. Pratense grew normally, while the growth of M. Sativa was significantly inhibited. The growth of A. Adsurgens was inhibited when the application amount of Cu~(2+) was≥800 mg·kg~(-1). An apphcation amount of≤1200 mg·kg~(-1) of Cu~(2+) pro-moted the N, P and K absorption of M. Sativa, but applying≤800 mg·kg~(-1) of Cu~(2+) had little effects on the N, P and K absorption of T. Pretense. The N, P and K contents of A. Adsurgens in-creased when the application amount of Cu~(2+) was ≤400 mg·kg~(-1), but decreased significantly when the Cu~(2+) application amount was≥800 mg·kg~(-1). When the application amount of Cd~(2+)was≤20 mg·kg~(-1) , the N, P and K contents in M. Sativa and T. Pratense stems and leaves and in A. Adsurgens stem increased, while those in A. Adsurgens leaf decreased. As a whole, the three leguminous plants all had certain tolerance to Cu~(2+) and Cd~(2+) stresses, especially T. Prat-ease to Cu~(2+) and M. Sativa to Cd~(2+).     

Synthesis of [2S-2-H]- and [2R-2-H]hexadecanoic acids

[2S-2-²H]- and [2R-2-²H]hexadecanoic acids were synthesized in overall yields of 59–67%. Methyl(2R)-2-hydroxyhexadecanoate, from the acid produced by Hansenula sydowiorum, was converted to the p-toluenesulphonate, reduced to trideutero alcohol with lithium aluminium deuteride and oxidized to [2S-2-²H]hexadecanoic acid. Methyl (2S)-2-chlorohexadecanoate, which was a by-product of tosylation and was also prepared by chlorinatioon of the hydroxy ester with thionyl chloride, on reduction and oxidation as before gave [2R-2-²H]-hexadecanoic acid. Intermediates were fully characterized, isotopic purity was 97% and optical purity was maintained throughout the syntheses. Attempts to reduce the tosyl or chloro groups, only, with sodium borodeuteride gave low yields probably due to preferential reduction of the ester group; 1,2-epoxyhexadecane was obtained from the tosylate and 2-chlorohexadecan-1-ol from the chloro ester.     

玉米O2/o2近等基因系胚乳中基因表达差异分析

对玉米Hz85(O2/O2)和 Hz85(o2/o2)以及S7913(O2/O2)和 S7913 (o2/o2)两种不同核背景下的近等基因系(NIL),采用cDNA芯片杂交技术研究玉米o2突变基因及赖氨酸形成和胚乳发生相关基因在RNA水平上的表达差异。在两套NILs中检测到共同的表达差异克隆87个,对其序列分析得到26个TUGs（tentative unique genes）、11个未命名蛋白和6个新序列。这些TUGs分别参与了生长发育、胁迫响应、物质运输、信号转导、电子传递链、细胞防御、代谢等细胞过程,以及作为细胞组分和贮存蛋白。基于O2/o2 NILs间胚乳发育中基因表达的差异,讨论了o2籽粒中的不透明粉质胚乳形成的分子机制。     

Determination of the extraction kinetics for the quantification of polyhydroxyalkanoate monomers in mixed microbial systems

For the first time, a systematic approach was conducted to determine the key factors influencing the kinetics of hydroxyalkanote (HA) extraction in biological systems. Six mixed microbial systems where polyhydroxyalkanoate (PHA) is produced were evaluated. Experiments were carried out for full-scale and lab-scale activated sludge systems using different configurations (containing floccular or granular sludge), as well as specific PHA accumulating cultures that contain high or low intracellular PHA fractions. The overall reaction was limited by the kinetics of the PHA hydrolysis in floccular cultures, whereas in granular cultures, it was limited by the cell lysis step. The monomeric composition of the polymer also had an impact on the HA extraction rate: higher acid concentration and a longer digestion time should be employed when cells accumulate monomers with more substituents, such as hydroxy-2-methylbutyrate (H2MB) and hydroxy-2-methylvalerate (H2MV). This study optimised the method for HA extraction, which impacts the assessment of the quantity and quality of PHA biopolymers.     

Activation of the UPR Protects against Cigarette Smoke-induced RPE Apoptosis through Up-Regulation of Nrf2

Recent studies have revealed a role of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) in the regulation of RPE cell activity and survival. Herein, we examined the mechanisms by which the UPR modulates apoptotic signaling in human RPE cells challenged with cigarette smoking extract (CSE). Our results show that CSE exposure induced a dose- and time-dependent increase in ER stress markers, enhanced reactive oxygen species (ROS), mitochondrial fragmentation, and apoptosis of RPE cells. These changes were prevented by the anti-oxidant NAC or chemical chaperone TMAO, suggesting a close interaction between oxidative and ER stress in CSE-induced apoptosis. To decipher the role of the UPR, overexpression or down-regulation of XBP1 and CHOP genes was manipulated by adenovirus or siRNA. Overexpressing XBP1 protected against CSE-induced apoptosis by reducing CHOP, p-p38, and caspase-3 activation. In contrast, XBP1 knockdown sensitized the cells to CSE-induced apoptosis, which is likely through a CHOP-independent pathway. Surprisingly, knockdown of CHOP reduced p-eIF2α and Nrf2 resulting in a marked increase in caspase-3 activation and apoptosis. Furthermore, Nrf2 inhibition increased ER stress and exacerbated cell apoptosis, while Nrf2 overexpression reduced CHOP and protected RPE cells. Our data suggest that although CHOP may function as a pro-apoptotic gene during ER stress, it is also required for Nrf2 up-regulation and RPE cell survival. In addition, enhancing Nrf2 and XBP1 activity may help reduce oxidative and ER stress and protect RPE cells from cigarette smoke-induced damage.     

大鼠心肌肌浆网的纯化及其性质研究

 用超声波破碎心肌细胞,差速离心法纯化大鼠心肌肌浆网(CSR)。SDS-聚丙烯酰胺凝胶电泳测得Ca~(2+)-ATPase分子量为98kD;电镜观察膜制备为完整的CSR微囊;标志酶哇巴因敏感型Na~(+),K~(+)-ATPase和叠氮化钠敏感型Mg~(2+)-ATPase活性表明膜制备中肌膜含量很低,但仍有线粒体污染。 用~(45)Ca~(2+)示踪微孔滤膜法研究Ca~(2+)跨膜转运,CSRCa~(2+)蓄集最大值为57nmol/mg蛋白。CSR Ca~(2+)-ATPase在4℃—21℃和21℃—49℃两区间反应活化能不同,前者大于后者。酶的最适pH为7.4。以ATP为底物,该酶有两个表观Km值:Km_1为3.7μmol/LKm_2为713μmol/L。     

Regulation of erythroid differentiation by miR-376a and its targets

Lineage differentiation is a continuous process during which fated progenitor cells execute specific programs to produce mature counterparts. This lineage-restricted pathway can be controlled by particular regulators, which are usually exclusively expressed in certain cell types or at specific differentiation stages. Here we report that miR-376a participates in the regulation of the early stages of human erythropoiesis by targeting cyclin-dependent kinase 2 (CDK2) and Argonaute 2 (Ago2). Among various human leukemia cell lines, miR-376a was only detected in K562 cells which originated from a progenitor common to the erythroid and megakaryotic lineages. Enforced expression of miR-376a or silencing of CDK2 and Ago2 by RNAi inhibits erythroid differentiation of K562 cells. Hematopoietic progenitor cells transduced with miR-376a showed a significant reduction of their erythroid clonogenic capacity. MiR-376a is relatively abundant in erythroid progenitor cells, where it reduces expression of CDK2 and maintains a low level of differentiation due to cell cycle arrest and decreased cell growth. Following erythroid induction, miR-376a is significantly down-regulated and CDK2 is released from miR-376a inhibition, thereby facilitating the escape of progenitor cells from the quiescent state into erythroid differentiation. Moreover, our results establish a functional link between miR-376a and Ago2, a key factor in miRNA biogenesis and silencing pathways with novel roles in human hematopoiesis.     

Direct regulation of IL-2 by curcumin

Interleukin-2 (IL-2) is a crucial growth factor for both regulatory and effector T cells. Thus, IL-2 plays a critical role in the stimulation and suppression of immune responses. Recently, anti-IL-2 antibodies (Abs) have been shown to possess strong IL-2 modulatory activities by affecting the interaction between IL-2 and IL-2 receptors. In this study, we screened an herbal library to identify a compound that regulates IL-2, which resulted in the identification of curcumin as a direct binder and inhibitor of IL-2. Curcumin is a phytochemical with well-known anti-cancer properties. In this study, curcumin mimicked or altered the binding pattern of anti-IL-2 Abs against IL-2 and remarkably inhibited the interaction of recombinant IL-2 with the IL-2 receptor α, CD25. Interestingly, curcumin neutralized the biological activities of IL-2 both in vitro and in vivo. In this report, we elucidated the unsolved mechanism of the anti-cancer effect of curcumin by identifying IL-2 as a direct molecular target. Curcumin, as a small molecule IL-2 modulator, has the potential to be used to treat IL-2 related pathologic conditions.     

Isolation and identification of urinary metabolites of AF-2 (3-(5-nitro-2-furyl)-2-(2-furyl)acrylamide) in rabbits

After oral administration of AF-2 (3-(5-nitro-2-furyl)-2-(2-furyl)acrylamide) to rabbits, the two unique metabolites, M-I and M-II, were isolated from the urine. M-I, yellow needles of mp 117°, was identified as a new type metabolite of nitrofuran derivative, 2-(β-carboxypropionyl)-3-(5-methylthio-2-furyl) acrylamide by its mass, ir and nmr spectrometries. M-II, yellow solid, appears to be cis-trans isomer of M-I considering from its uv and mass spectral data, and the behavior on tlc.