Induction of favism-like symptoms in the rat: Effects of vicine and divicine in normal and buthionine sulphoximine-treated rats

Rats were fed an adequate or a deficient diet and offered water or buthionine sulphoximine (BSO) solution for 2 weeks, and then the same diets with vicine for another week in experiment 1. BSO in combination with the deficient diet caused a marked decrease in blood glutathione (GSH) and growth retardation but failed to show any effects resulting from supplementation with vicine. In experiment 2 the rats were given an adequate diet and BSO as before, and injected intravenously with divicine (DV). Here again, BSO depressed rat growth, and so did DV. Each of the insults also caused haematological changes, especially a fall in GSH, but the most severe changes appeared in the group treated with both BSO and DV. A decrease in haematocrit and increases in adrenal and spleen weight were also noted. In experiment 3 the rats were injected with different doses of DV, without pretreatment with BSO. The main effect was a drop in blood GSH and haematocrit, and an increase in adrenal and spleen weights, all of which were dose-related. Administration of the higher doses of DV resulted in a severe cyanosis followed by death within a relatively short period of time.     

Multimer formation as a consequence of separate homodimerization domains: the human c-Jun leucine zipper is a transplantable dimerization module

Human c-Jun and c-Fos leucine zipper domains were examined fortheir ability to serve as autonomous dimerization domains aspart of a heterologous protein construct. Schistosoma japonicumglutathione S-transferase (GST) was fused to recombinant Junleucine zipper (rJunLZ) and Fos leucine zipper (rFosLZ) domains.SDS–PAGE ‘snapshot’ analyses based on disulphidelinkage of monomers demonstrated the ability of rJunLZ to functionas a dimerization motif in a foreign protein environment. Sterichindrance prevented formation of rJunLZ–GST::rFosLZ–GSTheterodimers whereas rJunLZ–GST::rFosLZ and rJunLZ::rFosLZ–GSTformed readily. Furthermore, rJunLZ–GST generated homodimerssuggesting fusion protein heterodimers interact differentlyto homodimers. Gel filtration chromatography confirmed thatGST is a dimer in solution and that attachment of a leucinezipper domain allows further interactions to take place. Sedimentationequilibrium analyses showed that GST is a stable dimer (K_a >10⁶ M^-1) with no higher multimeric forms. rFosLZ–GST weaklyassociates beyond a dimer (K_a {small tilde}4x10⁵ M^-1) and rJunLZ–GSTassociates indefinitely (K_a {small tilde}4x10⁶ M^-1), consistentwith an isodesmic model of association. The interaction of theseleucine zippers independently of GST association demonstratestheir utility in the modification of proteins when multimerformation is desired.     

邻苯二甲醛同步荧光衍生化法测定微量指血中还原型谷胱甘肽

采用微升（μL）级微量指血为检测样品,在未对样品去蛋白的条件下,用邻苯二甲醛（OPA）荧光衍生化法测定了微量静脉血中还原型谷胱甘肽（GSH）的含量.利用标准曲线法和标准加入法进行3次测定的均值分别为4.415μmol/L和5.417 5μmol/L,加标回收率为95.28%～97.18%,检测限为3.6×10-8 mol/L,可基本满足微量成分分析所要求的准确度.本研究为灵敏、简便和快速测定微量血样中GSH的含量提供了实验和方法学的依据.     

还原型谷胱甘肽提取方法初探

还原型谷胱甘肽(GSH)是一种天然的活性短肽，具有清理体内自由基等生理功能。为了寻找适合实验室应用的简便、易行的提取GSH的方法，以安琪活性干酵母为研究对象，以相似相容原理为理论依据，用热水抽提、甲酸抽提、乙醇抽提、低温抽提方法提取GSH，分析比较不同提取方法的提取效果。结果表明，热水抽提是一种比较理想的从酵母中提取谷胱甘肽的方法，其特点是耗时少、仪器简单、抽提液中GSH质量浓度高、经济且无污染。     

Water-gated phthalocyanine transistors: Operation and transduction of the peptide–enzyme interaction

The use of aqueous solutions as the gate medium is an attractive strategy to obtain high charge carrier density (10¹² cm⁻²) and low operational voltages (<1 V) in organic transistors. Additionally, it provides a simple and favorable architecture to couple both ionic and electronic domains in a single device, which is crucial for the development of novel technologies in bioelectronics. Here, we demonstrate the operation of transistors containing copper phthalocyanine (CuPc) thin-films gated with water and discuss the charge dynamics at the CuPc/water interface. Without the need for complex multilayer patterning, or the use of surface treatments, water-gated CuPc transistors exhibited low threshold (100 ± 20 mV) and working voltages (<1 V) compared to conventional CuPc transistors, along with similar charge carrier mobilities (1.2 ± 0.2) x 10⁻³ cm² V⁻¹ s⁻¹. Several device characteristics such as moderate switching speeds and hysteresis, associated with high capacitances at low frequencies upon bias application (3.4–12 μF cm⁻²), indicate the occurrence of interfacial ion doping. Finally, water-gated CuPc OTFTs were employed in the transduction of the biospecific interaction between tripeptide reduced glutathione (GSH) and glutathione S-transferase (GST) enzyme, taking advantage of the device sensitivity and multiparametricity.     

铁死亡的机制及其在淋巴瘤中的研究进展

淋巴瘤是常见的血液系统恶性肿瘤，对人类健康造成极大的威胁。目前淋巴瘤的治疗方法包括化疗、分子靶向治疗、造血干细胞移植等，但耐药和复发难治仍是待解决的问题。铁死亡是新发现的一种细胞死亡模式，与铁依赖性的脂质过氧化损伤相关。靶向铁死亡为抑制淋巴瘤进展提供了新思路。本文从铁死亡的起始信号、中间事件、效应阶段、防御机制来阐述铁死亡的机制并回顾了铁死亡在淋巴瘤中的研究进展，为铁死亡在淋巴瘤治疗方法的应用方面提供新的思路。     

15‐Methylene‐Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia

Recent studies suggest that leukemia stem cells (LSCs) play a critical role in the initiation, propagation, and relapse of leukemia. Herein we show that (?)‐15‐methylene‐eburnamonine, a derivative of the alkaloid (?)‐eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also decreases primary LSC frequency in vitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells. By the use of a novel humanized bone marrow murine model of leukemia (huBM/NSG), it was found to decrease progenitor cell engraftment.