A review on the hybrids of hydroxycinnamic acid as multi-target-directed ligands against Alzheimer’s disease

Alzheimer’s disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD.     

The regulation of necroptosis by ubiquitylation

Necroptosis is a programmed necrosis that is mediated by receptor-interacting protein kinases RIPK1, RIPK3 and the mixed lineage kinase domain-like protein, MLKL. Necroptosis must be strictly regulated to maintain normal tissue homeostasis, and dysregulation of necroptosis leads to the development of various inflammatory, infectious, and degenerative diseases. Ubiquitylation is a widespread post-translational modification that is essential for balancing numerous physiological processes. Over the past decade, considerable progress has been made in the understanding of the role of ubiquitylation in regulating necroptosis. Here, we will discuss the regulatory functions of ubiquitylation in necroptosis signaling pathway. An enhanced understanding of the ubiquitylation enzymes and regulatory proteins in necroptotic signaling pathway will be exploited for the development of new therapeutic strategies for necroptosis-related diseases.

     

微乳体系中11β-羟基甲羟孕酮的C1,2生物脱氢

为改善过程传质,提高甾类药物中间体11β-羟基甲羟孕酮C1,2生物脱氢转化率,采用简单节杆菌Arthrobacter simplex UR016菌株在Tween-80/乙醇/食油/水构成的微乳体系中进行生物脱氢,并考察了微乳体系组成、转化温度、投料浓度对脱氢反应的影响。结果表明:以菌体培养液作为水相,食油作为油相构建微乳体系,食油最适加量为10g/L,表面活性剂Tween-80加量为4g/L;底物经醇溶后水析投料,乙醇最适加量为发酵液体积的7%(V/V);最适转化温度为33oC;当底物浓度为4g/L时,在构建的微乳体系中转化46h,脱氢转化率达88.6%,与水相转化工艺相比提高了66.2%。在该体系中疏水性11β-羟基甲羟孕酮底物得到了有效的增溶和扩散,生物脱氢转化率明显提高。     

海南红厚壳花香气成分采集和TCT-GC-MS分析

用鲜花循环式动态顶空技术采集红厚壳鲜花的香气成分,TCT-GC-MS联用技术分析鉴定。4-羟基-2-丁酮,双烯酮,1、2-环氧-2-甲基丁烷,1、2-环氧-3-甲基丁烷,2-乙基戊烷,3-己醇,甲基环戊烷,2-丁醇等24个成分被检测出,占总离子流出峰面积的90.28%。并对结果进行了分析讨论。     

Effects of Apolipoprotein E Genotype on the Off-Line Memory Consolidation

Spontaneous brain activity or off-line activity after memory encoding is associated with memory consolidation. A few recent resting-state functional magnetic resonance imaging (RS-fMRI) studies indicate that the RS-fMRI could map off-line memory consolidation effects. However, the gene effects on memory consolidation process remain largely unknown. Here we collected two RS-fMRI sessions, one before and another after an episodic memory encoding task, from two groups of healthy young adults, one with apolipoprotein E (APOE) ε2/ε3 and the other with APOE ε3/ε4. The ratio of regional homogeneity (ReHo), a measure of local synchronization of spontaneous RS-fMRI signal, of the two sessions was used as an index of memory-consolidation. APOE ε3/ε4 group showed greater ReHo ratio within the medial temporal lobe (MTL). The ReHo ratio in MTL was significantly correlated with the recognition memory performance in the APOE ε3/ε4 group but not in ε2/ε3 group. Additionally, APOE ε3/ε4 group showed lower ReHo ratio in the occipital and parietal picture-encoding areas. Our results indicate that APOE ε3/ε4 group may have a different off-line memory consolidation process compared to ε2/ε3 group. These results may help generate future hypotheses that the off-line memory consolidation might be impaired in Alzheimer’s disease.     

Thf1 interacts with PS I and stabilizes the PS I complex in Synechococcus sp. PCC7942

Thylakoid formation1 protein (Thf1) is a multifunctional protein that is conserved in all photosynthetic organisms. In this study, we used the model cyanobacterium Synechococcus sp. PCC7942 (hereafter Synechococcus) to show that the level of Thf1 is altered in response to various stress conditions. Although this protein has been reported to be involved in thylakoid formation, the thylakoid membrane in the thf1 deletion strain (ΔThf1) was not affected. Compared with the WT, ΔThf1 showed reduced PS II activity, with increased levels of D1 under high light (HL) conditions, which was resulted from blocked D1 degradation by the FtsH protease and thus inhibits PS II repair. PS I was found to be more seriously affected than PS II in ΔThf1, even under low light conditions, suggesting that PS I damage could be the primary effect of thf1 deletion in Synechococcus. Further analysis revealed that the ΔThf1 mutant had a lower PS I subunit content and lower PS I stability under HL conditions. Further sucrose gradient fractionation of the membrane protein complexes and crosslinking and immunoblot analysis indicated that Thf1 interacts with PS I. Together, our results reveal that Thf1 interacts with PS I and thereby stabilizes PS I in Synechococcus.     

iQPR法处理水对SD鼠生物安全性的研究

iQPR技术处理污水是一项新型尖端的技术,此技术可以成功降低污水乃至受到污染的地下水中的各种污染指标。但是,iQPR技术处理污水尤其是地下水是否存在潜在的生物安全性问题有待于进一步研究。因此,为评估iQPR技术对生物安全性的影响,本研究首先分析了三种不同iQPR法处理水的水质成分;其次系统研究了iQPR水对SD鼠在个体水平、组织水平和病理形态学损伤的研究。研究表明:iQPR处理的水质成分较对照组普通饮用水好,在个体组织水平检测未见异常,尽管其中一组iQPR处理水造成了SD鼠的脾小体增大,但是可能的原因是水处理环节存在微生物污染现象,因此,初步认定此技术未造成SD大鼠的个体损伤。本研究为揭示iQPR处理的水对生物体的安全性评价提供一个理论依据。