Redirecting Killer T Cells through Incorporation of Azido Sugars for Tethering Ligands

The genetic expression of chimeric antigen receptors (CARs) on the surfaces of T cells enables the redirection of T cell specificity. To enhance the versatility of T cells as tumor-specific killers, we developed a nongenetic approach by which azide-containing sialic acids were metabolically incorporated into T cells to modify cellular sialyl glycans. After successful display of these moieties on the T cells, small-molecule ligands such as RGD and folate (as proof-of-concept, rather than supersized antibodies) were clicked orthogonally, leading to highly selective time- and dose-dependent cytotoxicity to integrin α_vβ₃- and folate-receptor-positive cells, respectively. This chemical approach provides a facile platform for rational design of tumor-specific cytotoxic T cells for targeted immunotherapy.     

H‐B‐E (hexanol‐butanol‐ethanol) fermentation for the production of higher alcohols from syngas/waste gas

CO, H₂, and CO₂ are major components of syngas and some industrial CO‐rich waste gases (e.g. waste gases from steel industries), besides some additional minor compounds. It was recently shown that those gases can be bioconverted, by acetogenic/solventogenic bacteria, into ethanol and higher alcohols such as butanol, but also hexanol, through the so‐called HBE fermentation. That process presents some advantages over existing chemical conversion processes. This paper reviews HBE fermentation from C1‐gases after briefly describing the more conventional ABE (acetone‐butanol‐ethanol) fermentation from carbohydrates by Clostridium acetobutylicum, in order to allow for comparison of both processes. Although acetone may appear in carbohydrate fermentation, alcohols are the only major end‐metabolites in the HBE process with Clostridium carboxidivorans. The few acetogenic bacteria known to metabolize C1‐gases and produce butanol or higher alcohols are described. Clostridium carboxidivorans has been used in most cases. Bioconversion of the gaseous substrates takes place in two stages, namely acidogenesis (production of acids) followed by solventogenesis (production of alcohols), characterized by different optimal fermentation conditions. Major parameters affecting each bioconversion stage as well as the overall fermentation process are analyzed. Although it has been claimed that acidification is required in ABE fermentation to initiate the solventogenic stage, strong acidification seems to some extent not to be a prerequisite for solventogenesis in the HBE process. Bioreactors potentially suitable for this type of bioconversion process are described as well. © 2017 Society of Chemical Industry     

Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction. The morphology of the mitochondria changed, clearly showing the damage induced by oxidative stress and the decreased membrane potential associated with the alterations of the mitochondrial function. The co-administration of geranylgeraniol (GGOH) reduced the inflammatory marker and the damage of the mitochondria, maintaining its shape and components. Our data allow us to speculate about the mechanism by which isoprenoids are able to rescue the inflammatory marker in neuronal cells, independently from the block of the mevalonate pathway, and about the fact that cell death is mitochondria-related.     

植物花青素通过JNK信号通路抗肿瘤机制研究进展

文章综述了JNK信号通路的组成及活化机制,总结了植物花青素通过该信号通路抑制乳腺癌、前列腺癌、肝癌等恶性肿瘤发生、增殖、侵袭和凋亡的能力,以期为植物花青素应用于功能食品和药品的开发提供依据。     

Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system.     

天麻素联合地塞米松保护缺糖缺氧诱导的H9C2细胞损伤

目的：探讨天麻素（gastrodin, GAS）联合地塞米松（dexamethasone, DEX）在缺糖缺氧诱导心肌细胞损伤中的作用及可能机制。方法：建立缺糖缺氧细胞（oxygen-glucose deprivation, OGD）模型,细胞分为5组,即正常对照组（normal group）,缺糖缺氧组（OGD group）,DEX组,GAS组,DEX+GAS组。利用CCK-8实验检测各组心肌细胞活性,利用比色法检测乳酸脱氢酶（LDH）的活性;利用TUNEL法检测各组心肌细胞的凋亡情况;利用ELISA实验检测各组心肌细胞培养液中炎性因子;利用Western blot检测各组心肌细胞中Notch1、Bax、Bcl-2及Beclin1的表达情况。结果：结果显示GAS与DEX联合使用可显著提高损伤心肌细胞的活性,减少心肌细胞的凋亡;降低促炎因子TNF-α、IL-6和IL-1β的产生及促进抑炎因子IL-10的产生,降低LDH的释放;Western blot结果显示GAS与DEX联合使用可促进Notch信号通路中Notch1的表达,显著降低受损心肌细胞中促凋亡蛋白Bax的表达,促进抑凋亡蛋白Bcl-2的表达,促进自噬相关基因Beclin1的表达。 结论：GAS与DEX联合使用,可能通过促进Notch信号通路的激活,促进其自噬,提高细胞的活性,抑制心肌细胞的凋亡,减轻炎症反应,从而减轻OGD诱导的心肌细胞损伤。     

滑动弧放电等离子体-溶液系统协同零价铁降解酸性橙Ⅱ

为探究等离子体-溶液系统联合零价铁(ZVI)Fenton反应对酸性橙Ⅱ(AOⅡ)的降解效果,考察ZVI对降解过程的促进作用及降解机理,建立了滑动弧等离子-溶液系统进行了实验研究。以质量浓度200 mg/L的AOⅡ为例,改变ZVI投加量分别为0、4、7、10、13 g。结果显示ZVI投加量为10 g时,AOⅡ的降解程度最高,为97.8%。等离子体-溶液系统中滑动弧放电产生的H2O2与加入的ZVI结合发生Fenton反应,AOⅡ降解过程遵守一级动力学规律。对比不加入ZVI时的AOⅡ反应速率常数,加入10 g ZVI后初始质量浓度为100、150、200、250、300 mg/L的AOⅡ反应速率常数分别提高了12.9%、31.0%、39.4%、44.3%、47.8%。溶液化学需氧量(COD)去除率也表明了在降解过程中加入ZVI能够有效地提高降解率。运用色谱-质谱联用仪(GC-MS)测定了AOⅡ的降解机理,认为*OH攻击AOⅡ分子上与萘环相连的—N N—键,导致—N N—键的断裂,并经过一系列的氧化过程后形成无机小分子物质。     

重组人促红细胞生成素对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制研究

目的 探讨重组人促红细胞生成素（recombinant human erythropoietin,rh-EPO）对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制.方法 将人乳腺癌 MDA-MB-231 细胞进行培养.传至5～6代,细胞生长状态稳定后,收集人乳腺癌 MDA-MB-231细胞用于MTT实验.采用MTT法检测 5 组（阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组）MDA-MB-231细胞增殖的情况.用10 μmol·L-1p38MAPK抑制剂SB203580、ERK抑制剂U0126、JNK抑制剂SP600125和NF-κB 抑制剂PDTC预处理人乳腺癌 MDA-MB-231 细胞后,用MTT法检测经100、200、300和400 U·mL-1的rh-EPO（PDTC＋EPO 组、SB203580＋EPO 组、SP600125＋EPO组和U0126＋EPO组）诱导后细胞增殖的情况.结果 阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72 h PI值分别为：1.000 0±1.000 0、1.231 8±0.133 0、1.323 9±0.136 0、1.351 7±0.146 0和1.423 1±0.084 0;96 h PI值分别为：1.000 0±1.000 0、1.352 5±0.036 0、1.359 7±0.112 0、1.387 2±0.063 0和1.410 8±0.060 0.rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72、96 h PI值与阴性对照组比较差异均有统计学意义（均P＜0.05）.PDTC＋EPO 组、SB203580＋EPO 组72、96 h PI值均较EPO组明显降低（均P＜0.05）,SP600125＋EPO组、U0126＋EPO组72、96 h PI值与EPO组比较差异均无统计学意义（均P＞0.05）.结论 rh-EPO可能是通过NF-κB、MAPK传导通路发挥效应,促进人乳腺癌MDA-MB-231细胞增殖.