| 1. |
- Li, Yang, et al.
(författare)
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VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats.
- 2008
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 118:3, s. 913-923
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Tidskriftsartikel (refereegranskat)abstract
- Despite its early discovery and high sequence homology to the other VEGF family members, the biological functions of VEGF-B remain poorly understood. We revealed here a novel function for VEGF-B as a potent inhibitor of apoptosis. Using gene expression profiling of mouse primary aortic smooth muscle cells, and confirming the results by real-time PCR using mouse and rat cell lines, we showed that VEGF-B inhibited the expression of genes encoding the proapoptotic BH3-only proteins and other apoptosis- and cell death-related proteins, including p53 and members of the caspase family, via activation of VEGFR-1. Consistent with this, VEGF-B treatment rescued neurons from apoptosis in the retina and brain in mouse models of ocular neurodegenerative disorders and stroke, respectively. Interestingly, VEGF-B treatment at the dose effective for neuronal survival did not cause retinal neovascularization, suggesting that VEGF-B is the first member of the VEGF family that has a potent antiapoptotic effect while lacking a general angiogenic activity. These findings indicate that VEGF-B may potentially offer a new therapeutic option for the treatment of neurodegenerative diseases.
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| 2. |
- Tian, Yu-Peng, et al.
(författare)
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Investigations and facile synthesis of a series of novel multi-functional two-photon absorption materials
- 2007
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 17:34, s. 3646-3654
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Tidskriftsartikel (refereegranskat)abstract
- Six centrosymmetric D-(pi-A)(3) structural triphenylamine derivatives that can be used as two- photon photopolymerization and optical data storage chromophores, tris[ 4-( 4- pyridylethenyl) phenyl] amine ( 1), tris[ 4-( 2- pyridylethenyl) phenyl] amine ( 2), tris( 4- cyanoethenylphenyl) amine ( 3), tris[ 4- butylacrylatephenyl] amine ( 4), tris[ 4- methylacrylatephenyl] amine ( 5) and tris[ 4- acrylicethenylphenyl] amine ( 6), have been successfully synthesized via a triple palladium-catalyzed Heck coupling reaction, and the novel chromophores were fully characterized by elemental analysis, IR, (1)H-NMR and ESIMS. The structure for 3 was determined by single crystal X-ray diffraction study. One- and two-photon absorption and fluorescence in various solvents were experimentally investigated. Two-photon initiated polymerization microfabrication and optical data recording experiments were carried out under 780 nm laser radiation, and the possible polymerization mechanism is discussed based on theoretical calculations. All the six chromophores have relatively large two-photon absorption crosssections, and exhibit optical memory and highly efficient two-photon initiated polymerization abilities.
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| 3. |
- Zhang, Fan, et al.
(författare)
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VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:15, s. 6152-6157
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Tidskriftsartikel (refereegranskat)abstract
- VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
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| 4. |
- Zhu, Li-Hua, et al.
(författare)
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Can Arabidopsis AP1 Gene Shorten the Juvenility of Apple?
- 2009
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Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; 829, s. 259-264
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Konferensbidrag (refereegranskat)abstract
- Shortening of the juvenile phase is of great importance for apple breeding. Compared to conventional breeding methods, gene technology is more straightforward in reducing juvenility, as it can directly regulate expression of flowering-time genes. In model plant Arabidopsis, a number of flowering-time genes have been identified and characterised. Some of them have also been isolated from other species. Regulation of these genes has been proved to promote early flowering in a number of plant species. In this study, we have introduced the Arabidopsis APETALA1 (AP1) gene into the apple rootstock M26. The transgenic plants have been grown in the greenhouse for two years; however, no early flowering has been observed, although the AP1 gene is constitutively expressed in the transgenic clones, confirmed by RT-PCR analysis.
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| 5. |
- Zhu, Li-Hua, et al.
(författare)
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Plant Size Control in Apple through Genetic Engineering
- 2009
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Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; 839, s. 689-694
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Konferensbidrag (refereegranskat)abstract
- Tree size control is essential for modern apple production. Chemical controls and different managements have been practically used in commercial production of apple rootstocks and cultivars in order to generate dwarf trees. However, these practices are either inefficient or unfriendly to human health and environment. In contrast, genetic engineering offers a better possibility to improve plant properties. By introducing well-characterised genes that control the growth vigour, it is possible to dwarf an existing genotype without disturbing its main genetic background. Up to now, some genes have been introduced into different plant species and proved to be effective in reducing plant size. Among the genes tested, the rolC, gai and GA oxidase have shown to be able to reduce plant size in most cases. In our previous studies, we have introduced the rolC and gai genes into apple rootstocks and cultivars. Both in vitro and grown analysis in greenhouse have shown that transgenic plants with one of these genes did display reduced plant height in most cases. Since plant height is mainly controlled by gibberellins, regulation of GA biosynthesis would be a better way to control plant size in the future.
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| 6. |
- Clarke, David, et al.
(författare)
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Addressing the challenge of legitimate international comparisons of classroom practice
- 2007
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Ingår i: International Journal of Educational Research. - : Elsevier BV. - 0883-0355 .- 1873-538X. ; 46:5, s. 280-293
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we address the choice of suitable instructional units that might serve as the basis for cross-cultural analyses of classroom practice. Our argument draws on analyses undertaken as part of the Learner's Perspective Study (LPS). The database comprised a three-camera video record of sequences of 10 consecutive lessons in each classroom, supplemented by post-lesson video-stimulated interviews with teachers and students: a total of over 180 videotaped lessons, over 50 teacher interviews and almost 400 student interviews. The results of these analyses challenge the suitability of the lesson as the unit of comparative analysis. In particular, the location of the lesson in the topic sequence is seen to be a key influence on the lesson's structure, critically affecting the teacher's deployment of the constituent activities that we have called ‘lesson events.' The lesson event is proposed as an alternative unit of international comparative analysis of classroom practice.
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| 7. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 8. |
- Guo, Xiao-Hua, et al.
(författare)
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Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells
- 2006
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 114:12, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.
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| 9. |
- Hua, Dong, et al.
(författare)
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Small interfering RNA-directed targeting of toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity
- 2009
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 46:15, s. 2876-2884
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Tidskriftsartikel (refereegranskat)abstract
- A major cause of tumor treatment failure is cancer cell metastasis. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we investigated the biological roles of TLR4 in prostate metastatic cell invasion and survival, and the potential of gene silencing of TLR4 using small interfering RNA (siRNA) for treatment of cancer. In cultured human prostate cancer cell lines, TLR4 were higher PC3 and DU145 as compared with the poorly metastatic LNCaP indicating that up-regulation of TLR4 was positively correlated with metastasis of tumor cell. In the highly metastatic cancer cell PC3, gene silencing of TLR4 using siRNA significantly inhibited TLR4 mRNA expression and protein level. Knockdown of TLR4 in PC3 cells resulted in a dramatic reduction of tumor cell migration and invasion as indicated by a Matrigel invasion assay. Furthermore, TLR4 siRNA suppressed cell viability and ultimately caused the induction of apoptotic cell death. The effects were associated with abrogating TLR4-mediated signaling to downstream target molecules such as myeloid differentiation factor 88 (MyD88), adaptor-inducing IFN-beta (TRIF), and interferon regulatory factor-1 (IRF-1). In a mouse prostate cancer model, administration with the plasmid construct expressing siRNA for TLR4 obviously inhibited established tumor growth and survival. These studies revealed evidence of a multifaceted signaling network operating downstream of TLR4-mediated tumor cell invasion, proliferation, and survival. Thus, RNA interference-directed targeting of TLR4 may raise the potential of its application for cancer therapy.
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| 10. |
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