Serine and arginine rich splicing factor 1:a potential target for neuroprotection and other diseases

Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.

相转移催化法合成α-紫罗兰醇-β-D-葡萄糖苷工艺研究

以α-紫罗兰酮为原料,经选择性还原得到α-紫罗兰醇,α-紫罗兰醇与溴代四乙酰葡萄糖在相转移催化剂四丁基溴化铵(TBAB)作用下进行反应得到α-紫罗兰醇-2,3,4,6-四-O-乙酰基-β-D-葡萄糖苷,最后脱去乙酰基得到目标糖苷.糖苷化反应适宜的反应条件为:以TBAB为相转移催化剂,用量为10%(摩尔百分比);以氯仿-水为反应溶剂;n(溴代四乙酰葡萄糖)∶n(α-紫罗兰醇)=1.6∶1;反应温度60℃;反应时间8 h.该条件下糖苷化反应产率为30%.目标化合物经FT-IR,1H NMR,ESI-MS确证为β-构型.

Group Ⅱ p21-activated kinases as therapeutic targets in gastrointestinal cancer

P21-activated kinases(PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group Ⅰ(PAK1-3) and group Ⅱ(PAK4-6). Focus is currently shifting from group Ⅰ PAKs to group Ⅱ PAKs. Group Ⅱ PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group Ⅱ PAKs have become popular potential drug target candidates. However, few group Ⅱ PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and "drug-like" properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group Ⅱ PAKs, the importance of group Ⅱ PAKs in the development and progression of gastrointestinal cancer, and smallmolecule inhibitors of group Ⅱ PAKs for the treatment of cancer.

The Effects of Ground and Treadmill Running on Energy Metabolism and Muscle Contractile Properties:A Randomized Cross-Over Study

Purpose This study aimed to compare the effects of ground and treadmill running on energy metabolism and muscle con-tractile properties,providing a basis for the general public to choose running venues.Methods Ten male college students(age,20.10±1.53 years;height,176.20±5.49 cm;weight,72.14±8.25 kg;body fat percent,12.41%±4.65%)were recruited in this study.Energy expenditure(EE)was measured using the accelerometer(GT9X)combined with specific estimation equations.Average heart rate(HR)was measured using a heart rate band(Polar).Muscle contractile properties were assessed by measuring muscle displacement(Dm)and contraction velocity(Vc)using tensiomyography(TMG-S1).Blood glucose(Glu)and lactate(Lac)were measured by portable devices(eB-G and Lactate Scout).The running speed was 9 km/h and the duration was 25 min.Two-way ANOVA(protocol×time)was used to analyze the effect of running protocols on energy metabolism and muscle contractile properties.Results EE of treadmill running was significantly higher than EE of ground running(protocol main effect,P<0.001),and HR of treadmill running was significantly higher than that of ground running in the first testing time(protocol simple effect,P=0.026;protocol×time interaction P=0.043).The decrease in Dm of the rectus femoris after treadmill running was significantly higher than that of ground running(protocol main effect,P=0.009).The interaction of different running protocols and testing times on Lac was significant(P=0.025),but all results of the simple effects analysis were not statisti-cally significant(P>0.05).Conclusion Our study found a difference in energy expenditure between treadmill and ground running at 9 km/h with duration of 25 min.In addition,treadmills are more likely to cause a decrease in muscle displacement distance of the rectus femoris measured after exercise than ground running.Future studies are needed to further investigate whether the differences are induced by internal metabolism or the environmental conditions of running.

Using pipette tips to readily generate spheroids comprising single or multiple cell types

Three-dimensional(3D)cell culture methods have been validated that can replicate the tumor environment in vivo to a large extent,providing an effective tool for studying tumors.In this study,we demonstrated the use of standard laboratory pipette tips as micro vessels for generating 3D cell spheroids.No microfabrication or wet-chemistry surface modifications were involved in the procedure.Spheroids consisting of single or multiple cell types were generated within 24 h just by pipetting and incubating a cell suspension in pipette tips.Scanning electron microscope and optical microscope proved that the cells grew together tightly,and suggested that while gravity force might have initiated the sedimentation of cells at the bottom of the tip,the active aggregation of cells to form tight cell-cell interactions drove the formation of spheroids.Using common laboratory micropipettes and pipette tips,the rate of spheroid generation and the generation reproducibility was characterized from five boxes each with 80 tips.The ease of transferring reagents allowed modeling of the growth of microvascular endothelial cells in tumor spheroids.Moreover,the pairing and fusion of tumor spheroids could be manipulated in the pipette tips,suggesting the potential for building and assembling heterogeneous micro-tumor tissues in vitro to mimic solid tumors in vivo.This study demonstrated that spheroids can be readily and cost-effectively generated in standard biological laboratories in a timely manner using pipette tips.

Carbon sequestration benefits of the grain for Green Program in the hilly red soil region of southern China

Soil erosion disturbs not only the global carbon cycle,but it is a complex environmental problem.Revegetation could reduce carbon emission by controlling soil erosion and increase carbon sequestration and accumulation by fixing carbon in vegetation and soil.The Grain for Green Program(GFGP)of China is the largest ecological restoration program in the world closely related to land-use/land-cover change(LUCC).Systematically assessing the carbon sequestration benefit of GFGP is crucial for a better understanding of the effects of implementing GFGP and providing reasonable vegetation management.Therefore,we selected the hilly red soil region(HRSR)of southern China as a study area,which is one of the main ecologically vulnerable areas in China.We assessed the carbon sequestration in the GFGP area of the HRSR using the InVEST(Integrated Valuation of Environmental Services and Tradeoffs)model based on land-use/land-cover datasets during 2000e2015.Our results show that implementing GFGP is conducive to the enhancement of carbon sequestration services.Total carbon sequestration showed an increasing trend at a rate of 15.43%from 2000 to 2015.The most significant change mainly happened in Hunan Province with the shortest implementation time.The carbon sequestration of each carbon pool(namely aboveground biomass,belowground biomass,soil,and dead organic matter)also increased slightly.Additionally,for carbon sequestration,unused land converted to forest land is the most effective LUCC.This study can provide scientific support for the management and implementation of GFGP in the HRSR of China.

巨噬细胞参与反复潜水引起的肺损伤

目的:探索反复潜水引起肺损伤的炎症机制以及吸入高浓度氢气(HCH)对这种损伤的治疗作用。创新点:本研究首次在小鼠体内建立并评估减压诱导肺损伤(DILI)模型;首次探索巨噬细胞在DILI中的作用;首次探索呼吸HCH对于DILI的治疗作用。方法:将雄性C57小鼠随机分为对照组、DILI组和HCH组。DILI组于600 k Pa压力下暴露60 min,连续3d。HCH组在减压处理后吸入HCH(66.7%H2+33.3%O2)干预。减压操作6 h后检测小鼠肺功能和小鼠肺干湿比,取小鼠肺组织固定进行苏木精-伊红染色,并取小鼠全血进行血细胞计数实验。取小鼠肺组织提取蛋白并提取血清,采用酶联免疫吸附测定(ELISA)检测炎症因子与趋化因子,并使用蛋白质免疫印迹(western blotting)试验测定小鼠肺内小鼠含生长因子样模体粘液样激素样受体(F4/80)、巨噬细胞甘露糖受体(CD206)和诱导型一氧化氮合酶(i NOS)的表达量。使用免疫组化检测小鼠肺组织切片内F4/80、CD206和i NOS的阳性细胞的比例。提取小鼠肺组织内总信使核糖核酸(m RNA),使用荧光实时定量聚合酶链反应测定极化标记蛋白CD206和i NOS以及炎症因子TNF-α和IL-10的基因表达量。结论:多次减压可导致肺水肿、组织结构破坏和肺功能下降,病变程度和减压次数有关,证明模型建立成功。DILI可以诱导肺内和循环炎症反应的激活,巨噬细胞可能向肺内迁移趋化并向不同亚型极化,极化后的巨噬细胞M1与M2分别参与炎症激活与炎症抑制的过程。吸入HCH可以显著改善小鼠肺损伤,降低肺内炎症反应,抑制巨噬细胞向M1亚型极化并促进其向M2亚型极化,从而证明吸入HCH对于DILI具有治疗作用。

甲烷治疗疾病效应及其机制

甲烷是最简单的有机烃类,由1个碳原子和4个氢原子组成。甲烷在沼气、家畜反刍和可燃冰中含量丰富。甲烷在疾病治疗中的作用还未被大家熟悉。最近的研究表明甲烷可以治疗多种疾病,包括缺血再灌注损伤和炎症疾病。甲烷治疗疾病的机制可能包括抗氧化、抗炎症和抗凋亡。本文将描述甲烷对不同疾病的治疗效应,总结甲烷治疗效应的可能作用机制,并讨论甲烷在低氧环境下产生的目的。最后,我们也将提出甲烷研究的前景及探索方向。

Phosphatase and tensin homologue:a therapeutic target for SMA

Spinal muscular atrophy(SMA)is one of the most common juvenile neurodegenerative diseases,which can be associated with child mortality.SMA is caused by a mutation of ubiquitously expressed gene,Survival Motor Neuron1(SMN1),leading to reduced SMN protein and the motor neuron death.The disease is incurable and the only therapeutic strategy to follow is to improve the expression of SMN protein levels in motor neurons.Significant numbers of motor neurons in SMA mice and SMA cultures are caspase positive with condensed nuclei,suggesting that these cells are prone to a process of cell death called apoptosis.Searching for other potential molecules or signaling pathways that are neuroprotective for central nervous system(CNS)insults is essential for widening the scope of developmental medicine.PTEN,a Phosphatase and Tensin homologue,is a tumor suppressor,which is widely expressed in CNS.PTEN depletion activates anti-apoptotic factors and it is evident that the pathway plays an important protective role in many neurodegenerative disorders.It functions as a negative regulator of PIP3/AKT pathway and thereby modulates its downstream cellular functions through lipid phosphatase activity.Moreover,previous reports from our group demonstrated that,PTEN depletion using viral vector delivery system in SMN delta7 mice reduces disease pathology,with significant rescue on survival rate and the body weight of the SMA mice.Thus knockdown/depletion/mutation of PTEN and manipulation of PTEN medicated Akt/PKB signaling pathway may represent an important therapeutic strategy to promote motor neuron survival in SMA.