Therapeutic Role of Fibroblast Growth Factor 21 (FGF21) in the Amelioration of Chronic Diseases

International Journal of Peptide Research and Therapeutics - Fibroblast growth factor-21 (FGF21) is a member of the family of fibroblast growth factors (FGFs). FGF21 (synthesized by many organs)...     

9R穿膜肽可增强P53抗肿瘤效果

为解决P53蛋白难以进入细胞内部发挥治疗作用的瓶颈难题.将p53基因融合插入带有9个精氨酸作为穿膜肽的表达载体中表达融合蛋白CPPs-P53,并与没有穿膜肽的P53蛋白进行比较,利用Western blotting方法检测蛋白的表达情况,MTT及Annexin V/PI双染法检测细胞生长抑制率及细胞凋亡率.Western blotting检测表明已成功在原核表达系统中表达融合蛋白CPPs-P53和P53蛋白,且蛋白纯度均已达到90％以上;MTT检测表明,P53蛋白对肿瘤细胞的生长虽有一定的抑制作用,但融合蛋白CPPs-P53与之相比,对肿瘤细胞生长的抑制效果显著增强,细胞生长抑制率有明显的提升,并且细胞生长抑制率呈现剂量依赖性;Annexin V/PI双染检测细胞凋亡情况也表明P53虽可以在一定程度上诱导肿瘤细胞的凋亡,但与P53蛋白相比较,融合蛋白CPPs-P53诱导的凋亡细胞明显增加,凋亡率是P53蛋白的2～3倍.由此说明在抑制肿瘤细胞的生长和诱导细胞凋亡方面,CPPs-P53比没有穿膜肽的P53蛋白的效果更显著.     

荚蒾属植物花期物候及生长对引种地年际气候波动的响应

专属引种植物的物候及生长研究能够掌握特定物候相在专属水平上的阈值,并为评估引种专属的适应潜力提供参考。通过对中国科学院植物研究所北京植物园内引种多年的9种荚蒾（Viburnum）的花期及2种荚蒾的生长动态进行观测,分析讨论了花期对冬春两季异常低温的响应及营养与生殖生长的关联机制。结果表明：2009–2010年冬春异常低温后,荚蒾始花期的整体延迟是由春季环境热量供应不及时所致,种间延迟程度的差异则与原产地的气候有紧密联系：分布于寒温带地区的欧洲绣球（V.opulus）和修枝荚蒾（V.burejaeticum）延迟天数最少（分别为10和12天）,分布于我国亚热带的琼花（V.macrocephalum）和桦叶荚蒾（V.betulifolium）延迟天数最多（分别为21和26天）。荚蒾花前有效积温介于39–368°C之间。经历异常低温后,花前有效积温呈上升和下降两种格局,与物种冷量和热量的内在需求有关。荚蒾属植物的生殖与营养生长呈现两种关联方式,早花种类开花座果伴随着营养生长的竞争,晚花种类花后即出现营养生长的支持,对果实发育的保障性较强。     

Polycyclic aromatic hydrocarbon o-quinones inhibit the activity of the catalytic fragment of protein kinase C

Polycyclic aromatic hydrocarbons (PAHs) require metabolic activation to exert their carcinogenic effects. PAH trans-dihydrodiol proximate carcinogens are oxidized by aldo-keto reductases (AKRs) to their corresponding reactive and redox-active o-quinones which may have the properties of initiators and promoters. To determine whether these o-quinones target protein kinase C (PKC), their effects on human recombinant PKCalpha and PKCdelta and the catalytic fragment of rat brain PKC were determined. Naphthalene-1,2-dione (NP-1,2-dione), benzo[a]pyrene-7,8-dione (BP-7,8-dione), and 7,12-dimethylbenz[a]anthracene-3,4-dione (DMBA-3,4-dione) potently inhibited (IC(50) values 3-5 microM) the basal and stimulated activity of the holoenzymes PKCalpha and PKCdelta in a dose-dependent manner. Inhibition of PKC by BP-7,8-dione was observed irrespective of whether PKCalpha activity was stimulated with phorbol 12-myristate 13-acetate (PMA), phosphatidylserine (PS), or Ca(2+) or whether PKCdelta was stimulated with phorbol 12-myristate 13-acetate (PMA) or phosphatidylserine (PS), suggesting that the inhibition was not cofactor-specific. All three quinones inhibited the catalytic fragment of PKC in vitro, yielding identical IC(50) values (3-5 microM), indicating that they interact with the catalytic domain of PKC rather than the cofactor/activator sites. In contrast, no effect on either the holoenzyme or the catalytic fragment was observed with the corresponding PAH trans-dihydrodiols, indicating that inhibition was o-quinone-specific. Irreversible inhibition of the catalytic fragment of PKC was observed since activity could not be restored by dialysis, suggesting that arylation of the fragment had occurred. NP-1,2-dione and BP-7,8-dione also suppressed PKC activity in human breast cancer MCF-7 cell lysates which express PKCalpha, -beta, -delta, -epsilon, -iota, and -lambda isozymes. These data suggest that PAH o-quinones, generated by AKRs, may affect cellular signaling through suppression of the activity of PKC isoforms.     

FGF21 treatment ameliorates alcoholic fatty liver through activation of AMPK-SIRT1 pathway

Fibroblast growth factor 21 （FGF21）, a recently identified member of the FGF superfamily, is mainly secreted from the liver and adipose tissues and plays an important role in improving metabolic syndrome and homeostasis. The aim of this study is to evaluate the role of FGF21 in alcoholic fatty liver disease （AFLD） and to determine if it has a therapeutic effect on AFLD. In this paper, we tested the effect of FGF21 on alcohol-induced liver injury in a murine model of chronic ethanol gavage and alcohol-treated HepG2 cells. Male KM mice received single dose of 5 g/kg ethanol gavage every day for 6 weeks, which induced sig- nificant fatty liver and liver injury. The alcohol-induced fatty liver cell model was achieved by adding ethanol into the medium of HepG2 cell cultures at a final concentration of 75 mM for 9 days. Results showed that treatment with recombinant FGF21 ameliorated alcoholic fatty liver and liver injury both in a murine model of chronic ethanol gavage and alcohol-treated HepG2 cells. In addition, FGF21 treatment down-regulated the hepatic expression of fatty acid synthetic key enzyme, activated hepatic AMPK- SIRT1 pathway and significantly down-regulated hepatic oxidative stress protein. Taken together, FGF21 corrects multiple metabolic parameters of AFLD in vitro and in vivo by activation of the AMPK-SIRT1 pathway.     

Early priority effects of occupying a nutrient patch do not influence final maize growth in intensive cropping systems

Plant and Soil - Priority effects can be caused by an individual plant within a population that is the first to occupy and explore nutrient patches. However, the magnitude of priority effects of...     

Hydatid disease in China

Hydatid disease is one of the world's most geographically widespread zoonoses. It is present on all inhabited continents and occurs in tropical, subtropical, temperate, sub-arctic and arctic regions. The two countries with the greatest areas over which transmission occurs are almost certainly the Soviet Union and China. Until recently, however, very little information about hydatidosis in China was available outside the country(1). Since the 'open-door' policy over the past few years the great importance of hydatid disease in north and western China is gradually being realized.     

Reconstruction of Microbial Haplotypes by Integration of Statistical and Physical Linkage in Scaffolding

DNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or “haplotypes.” However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics, and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here, we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis.     

FGF21 ameliorates hepatic fibrosis by multiple mechanisms

Molecular Biology Reports - Previous study reports that fibroblast growth factor 21 (FGF21) could ameliorate hepatic fibrosis, but its mechanisms have not been fully investigated. In this study,...