The therapeutic potential of G-CSF in pressure overload induced ventricular reconstruction and heart failure in mice

In animal models of clinical entities causative of severe right and left ventricular (LV) pressure overload hypertrophy, increased density of the cellular microtubule network, through viscous loading of active myofilaments, causes contractile dysfunction that is normalized by microtubule depolymerization. In this study, 86 male mice were divided into seven groups. The transverse ascending aorta constriction (TAC) in six groups were performed in order to make heart failure model. Mice in each group were injected with G-CSF or/and telmisartan subcutaneously at different time respectively. Results showed that reduction in left ventricular volume and improved function persisted at 2 week, but recurrent dilatation at 4 weeks was associated with a loss of functional improvement. Compared with PBS group, the expression of VEGF protein and HIF-1 mRNA were significantly higher in mice injected with G-CSF or/and telmisartan (P < 0.05). The expression of p53 mRNA, myocardial fibrosis and mortality were significantly lower in mice injected with G-CSF or/and telmisartan (P < 0.05). It could be concluded that G-CSF can delay the progression of pressure overload induced ventricular reconstruction and heart failure in mice.     

凝溶蛋白对骨骼肌天然细肌丝的作用

凝溶蛋白是Ｆ－肌动蛋白丝的钙依赖性切割性蛋白质．经过焦磷酸溶液选择性抽提和微酸性介质的有效分离,可以得到纯度较高的天然细肌丝．在Ｃａ２＋存在时,凝溶蛋白可以切割天然细肌丝．但是,凝溶蛋白对天然细肌丝的作用时程与其对Ｆ－肌动蛋白丝的作用有着显著差异,提示细肌丝中的非肌动蛋白蛋白质可能影响了凝溶蛋白对天然细肌丝的结合或者切割速率．     

Clinical and molecular findings in osteoporosis-pseudoglioma syndrome

Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) cause autosomal recessive osteoporosis-pseudoglioma syndrome (OPPG). We sequenced the coding exons of LRP5 in 37 probands suspected of having OPPG on the basis of the co-occurrence of severe congenital or childhood-onset visual impairment with bone fragility or osteoporosis recognized by young adulthood. We found two putative mutant alleles in 26 probands, only one mutant allele in 4 probands, and no mutant alleles in 7 probands. Looking for digenic inheritance, we sequenced the genes encoding the functionally related receptor LRP6, an LRP5 coreceptor FZD4, and an LRP5 ligand, NDP, in the four probands with one mutant allele, and, looking for locus heterogeneity, we sequenced FZD4 and NDP in the seven probands with no mutations, but we found no additional mutations. When we compared clinical features between probands with and without LRP5 mutations, we found no difference in the severity of skeletal disease, prevalence of cognitive impairment, or family history of consanguinity. However, four of the seven probands without detectable mutations had eye pathology that differed from pathology previously described for OPPG. Since many LRP5 mutations are missense changes, to differentiate between a disease-causing mutation and a benign variant, we measured the ability of wild-type and mutant LRP5 to transduce Wnt and Norrin signal ex vivo. Each of the seven OPPG mutations tested, had reduced signal transduction compared with wild-type mutations. These results indicate that early bilateral vitreoretinal eye pathology coupled with skeletal fragility is a strong predictor of LRP5 mutation and that mutations in LRP5 cause OPPG by impairing Wnt and Norrin signal transduction.     

豌豆中可与Gro EL抗体发生免疫学反应的热激诱导蛋白

通过Ｗｅｓｔｅｒｎ印渍方法,发现在豌豆（ＰｉｓｕｍｓａｔｉｖｕｍＬ．）叶存在一种高分子量的蛋白可与ＧｒｏＥＬ抗体发生免疫学反应,它含有两种亚基,分子量分别为６０．４ｋＤ（α）和６５．５ｋＤ（β）,具有弱的ＡＴＰａｓｅ活性。热激处理后此蛋白的表达升高３～４倍,但外源ＡＢＡ处理并不增加它的表达。用３５Ｓ标记蛋白和氯霉素抑制实验表明,此蛋白可能是在８０Ｓ核糖体上合成的胞质蛋白。     

Association of B3GNT5 Polymorphisms with Susceptibility to ETEC F4ab/ac in the White Duroc?×?Erhualian Intercross and 15 Outbred Pig Breeds

The B3GNT5 gene is a candidate for the F4ab/ac receptor conferring susceptibility to enterotoxigenic Escherichia coli (ETEC) F4ab/ac in pigs. In this study, we screened mutations in the complete coding region of the porcine B3GNT5 gene and identified four SNPs in the 3' untranslated regions. We genotyped the four SNPs across a large-scale White Duroc × Chinese Erhualian F2 resource population (total F2 = 755) and 292 purebred piglets representing 15 Chinese and Western breeds. We found that the g.1476G→A locus and haplotypes [A;T;G;T] and [A;G;G;T] had significant association with susceptibility to ETEC F4ac in the resource population. None of the B3GNT5 polymorphisms and haplotypes was associated with susceptibility to ETEC F4ab/ac in outbred piglets. This result, together with other reports, supports the conclusion that B3GNT5 is not the responsible gene encoding the ETEC F4ab/ac receptors.     

同型半胱氨酸对大鼠血管平滑肌细胞增殖的作用

血中同型半胱氨酸（ｈｏｍｏｃｙｓｔｅｉｎｅ,ＨＣＹ）浓度的升高已成为动脉粥样硬化发生的一个独立危险因子．为进一步阐明ＨＣＹ促进血管平滑肌细胞（ｖａｓｃｕｌａｒｓｍｏｏｔｈｍｕｓｃｌｅｃｅｌｓ,ＶＳＭＣｓ）增殖,从而引起动脉粥样硬化发生的机理．本实验采用细胞计数、３Ｈ－ＴｄＲ参入、细胞周期分析、Ｎｏｒｔｈｅｒｎ杂交方法证明,一定剂量的ＨＣＹ可促进离体培养的ＷＫＹ大鼠血管平滑肌细胞增殖,使其ＤＮＡ合成增加,细胞周期中Ｓ期细胞所占比例增加４３％,并促进ｃ－ｍｙｃ与ｃ－ｆｏｓ原癌基因ｍＲＮＡ表达增加．提示ＨＣＹ可能通过促进ＶＳＭＣｓ增殖而诱发动脉粥样硬化     

Heparan sulfate proteoglycans and heparin regulate melanoma cell functions

Background

The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi–radial growth phase–vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions.

Scope of review

This review will critically discuss the roles of HSPGs/heparin in melanoma development and progression.

Major conclusions

We have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis.

General significance

The current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.     

Design of a high-power collimating optical system based on Fresnel lenses

In light-emitting diode (LED) illumination (e.g., LED maritime lighting for ships), creating a uniform light environment for optical systems is an important challenge. In this study, we present a high-power collimating system based on Fresnel lenses, which allows high-brightness LED illumination in the earlier-mentioned remote distance. The work presented in this article focuses on improving the power, compacting the optical structure, and promoting the brightness of the spot. To prove the claims, the system with a total power of 1 kW is designed. The system consists of a 27 W LED array, a freeform surface lens array, and a confocal Fresnel lens array. In comparison with the traditional optical system, the optical structure shortens from 390 to 120 mm, and the divergent angle decreases from 3° to 2 $$. Meanwhile, the illuminance of the system is obtained as high as 230 lx at the near field of 200 m and 3.0 lx at the far field of 1.5 nautical miles. This new method provides a practical and effective way to solve the problem of low power, insufficient illuminance, and long optical structure for LED array illumination, which is suitable for remote illumination and guidance of ships.