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Neil Gerard Quigley Dr. Stefano Tomassi Dr. Francesco Saverio di Leva Dr. Salvatore Di Maro Dr. Frauke Richter Dr. Katja Steiger Prof. Dr. Susanne Kossatz Prof. Dr. Luciana Marinelli Dr. Johannes Notni 《Chembiochem : a European journal of chemical biology》2020,21(19):2836-2843
αvβ6 Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with αvβ6 integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the αvβ6-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH2) to enhance αvβ6 integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)3 showed a 28-fold higher αvβ6 affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC50 of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC50-based selectivity over the related integrin αvβ8 (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)3 holds promise for improved clinical PET diagnostics of carcinomas and fibrosis. 相似文献
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Wei-Jen Ting Wei-Wen Kuo Dennis Jine-Yuan Hsieh Yu-Lan Yeh Cecilia-Hsuan Day Ya-Hui Chen Ray-Jade Chen Viswanadha Vijaya Padma Yi-Hsing Chen Chih-Yang Huang 《International journal of molecular sciences》2015,16(10):25881-25896
Obesity is one of the major risk factors for nonalcoholic fatty liver disease (NAFLD), and NAFLD is highly associated with an increased risk of cardiovascular disease (CVD). Scholars have suggested that certain probiotics may significantly impact cardiovascular health, particularly certain Lactobacillus species, such as Lactobacillus reuteri GMNL-263 (Lr263) probiotics, which have been shown to reduce obesity and arteriosclerosis in vivo. In the present study, we examined the potential of heat-killed bacteria to attenuate high fat diet (HFD)-induced hepatic and cardiac damages and the possible underlying mechanism of the positive effects of heat-killed Lr263 oral supplements. Heat-killed Lr263 treatments (625 and 3125 mg/kg-hamster/day) were provided as a daily supplement by oral gavage to HFD-fed hamsters for eight weeks. The results show that heat-killed Lr263 treatments reduce fatty liver syndrome. Moreover, heat-killed Lactobacillus reuteri GMNL-263 supplementation in HFD hamsters also reduced fibrosis in the liver and heart by reducing transforming growth factor β (TGF-β) expression levels. In conclusion, heat-killed Lr263 can reduce lipid metabolic stress in HFD hamsters and decrease the risk of fatty liver and cardiovascular disease. 相似文献
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开发更高性能的钢铁材料是促进“双碳”目标达成的有效途径之一。引入碳扩散是制备超高强度-高塑性复合钢的有效方法。在课题组前期研究基础上,利用真空热轧的方式制备不同层数的复合钢。通过增加层数,减小了复合钢内各层的厚度,复合钢在1 150 ℃热轧复合后继续保温过程,实现碳元素从高碳层向低碳层的扩散。利用扫描电子显微镜、FEI-透射电子显微镜及X射线衍射仪对组织及相组成进行了分析,利用电子探针显微分析仪测量了元素分配情况,并进行了硬度和拉伸性能测试。结果表明,随着层数的增加,复合钢内碳元素分布发生了明显的变化,马氏体层内部的碳含量逐渐升高,奥氏体层内部的碳含量逐渐降低,碳元素浓度差逐渐降低。同时,复合钢的屈服强度、抗拉强度和总伸长率呈现出先增加后降低的趋势。当复合钢内层数为9、11层时,其强度和塑性均超过单层马氏体钢;均匀伸长率随复合钢层数的增加而逐渐提高,15层复合钢取得了最大值(约10.1%)。9层复合钢获得了最佳的强度和塑性组合,与单层马氏体钢相比,抗拉强度(1 733 MPa)和伸长率(23.6%)分别提高了60 MPa和7.1%;同时其塑性也超过了单层奥氏体钢。此外,随着层数的增加,也导致奥氏体层比例逐渐提高,导致15层复合钢的强度低于单层马氏体钢的强度。 相似文献
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CGCS2000坐标系是我国目前精度最高的坐标系,其推广使用具有重大意义。文中在安装并学习美国高精度GPS基线处理软件GAMIT软件基础上,以4个无坐标信息观测墩为例,进行观测数据采集与数据处理方案的设计,以期获取4个观测墩的CGCS2000坐标。最终结果表明,各质量指标均满足限差要求,且平差后最弱边中误差满足《工程测量规范》(GB50026-2007)三等工程控制网的要求。 相似文献
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Silvia Claros Gustavo A. Rico-Llanos José Becerra José A. Andrades 《International journal of molecular sciences》2014,15(7):11255-11274
Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF (recombinant human TGF)-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein)-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo. 相似文献
9.
Zhenghong Li Lu Zhang Weiming He Changle Zhu Jinsong Yang Meixiao Sheng 《International journal of molecular sciences》2014,15(7):12959-12971
Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson’s staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF. 相似文献
10.
Maria Ariza-Avidad Alejandra Nieto Alfonso Salinas-Castillo Luis F Capitan-Vallvey Gordon M Miskelly Michael J Sailor 《Nanoscale research letters》2014,9(1):410
We report the monitoring of porous silicon (pSi) degradation in aqueous solutions using a consumer-grade digital camera. To facilitate optical monitoring, the pSi samples were prepared as one-dimensional photonic crystals (rugate filters) by electrochemical etching of highly doped p-type Si wafers using a periodic etch waveform. Two pSi formulations, representing chemistries relevant for self-reporting drug delivery applications, were tested: freshly etched pSi (fpSi) and fpSi coated with the biodegradable polymer chitosan (pSi-ch). Accelerated degradation of the samples in an ethanol-containing pH 10 aqueous basic buffer was monitored in situ by digital imaging with a consumer-grade digital camera with simultaneous optical reflectance spectrophotometric point measurements. As the nanostructured porous silicon matrix dissolved, a hypsochromic shift in the wavelength of the rugate reflectance peak resulted in visible color changes from red to green. While the H coordinate in the hue, saturation, and value (HSV) color space calculated using the as-acquired photographs was a good monitor of degradation at short times (t < 100 min), it was not a useful monitor of sample degradation at longer times since it was influenced by reflections of the broad spectral output of the lamp as well as from the narrow rugate reflectance band. A monotonic relationship was observed between the wavelength of the rugate reflectance peak and an H parameter value calculated from the average red-green-blue (RGB) values of each image by first independently normalizing each channel (R, G, and B) using their maximum and minimum value over the time course of the degradation process. Spectrophotometric measurements and digital image analysis using this H parameter gave consistent relative stabilities of the samples as fpSi > pSi-ch. 相似文献