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111.
Peng Zhou Xinyu Zhang Mengqi Guo Rong Guo Lei Wang Zihao Zhang Zongwei Lin Mei Dong Hongyan Dai Xiaoping Ji Huixia Lu 《Journal of cellular and molecular medicine》2019,23(10):7088-7098
Vascular calcification (VC) is a pathological process underpinning major cardiovascular conditions and has attracted public attention due to its high morbidity and mortality. Chronic kidney disease (CKD) is a common disease related to VC. Ginsenoside Rb1 (Rb1) has been reported to protect the cardiovascular system against vascular diseases, yet its role in VC and the underlying mechanisms remain unclear. In this study, we established a CKD‐associated VC rat model and a β‐glycerophosphate (β‐GP)‐induced vascular smooth muscle cell (VSMC) calcification model to investigate the effects of Rb1 on VC. Our results demonstrated that Rb1 ameliorated calcium deposition and VSMC osteogenic transdifferentiation both in vivo and in vitro. Rb1 treatment inhibited the Wnt/β‐catenin pathway by activating peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), and confocal microscopy was used to show that Rb1 inhibited β‐catenin nuclear translocation in VSMCs. Furthermore, SKL2001, an agonist of the Wnt/β‐catenin pathway, compromised the vascular protective effect of Rb1. GW9662, a PPAR‐γ antagonist, reversed Rb1's inhibitory effect on β‐catenin. These results indicate that Rb1 exerted anticalcific properties through PPAR‐γ/Wnt/β‐catenin axis, which provides new insights into the potential theraputics of VC. 相似文献
112.
Claudia Karnthaler‐Benbakka Bettina Koblmüller Marlene Mathuber Katharina Holste Walter Berger Petra Heffeter Christian R. Kowol Bernhard K. Keppler 《化学与生物多样性》2019,16(1)
Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small‐molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B‐cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non‐cathepsin B‐cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B‐expressing cell lines Caki‐1 and RU‐MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B‐cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer. 相似文献
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Jinge Yang Guang Zhang Man Wu Qiquan Shang Lin Huang Huabei Jiang 《Journal of biophotonics》2019,12(6)
Monitoring the blood supply in the lower extremities is critical for individuals who are vulnerable to vascular dysfunction. Current clinical approaches are ineffective in observing hemodynamic changes in peripheral vessels. In this paper, we investigate the potential of photoacoustic tomography (PAT) as an alternative way to in vivo monitor hemodynamic changes in foot vessels. High spatial and temporal resolution maps of hemoglobin in major arteries and veins are shown. Results from twelve human subjects are presented here to visualize vascular perfusion of healthy volunteers in two age groups (young vs aged). Significant differences between the two groups are observed and verify the declining in vascular function with aging, highlighting the potential of PAT as a new tool to evaluate vascular function in the lower extremities. 相似文献
117.
Simon M. Smart Susan G. Jarvis Toshie Mizunuma Cristina Herrero‐Juregui Zhou Fang Adam Butler Jamie Alison Mike Wilson Robert H. Marrs 《Ecology and evolution》2019,9(22):12858-12868
Quantitative models play an increasing role in exploring the impact of global change on biodiversity. To win credibility and trust, they need validating. We show how expert knowledge can be used to assess a large number of empirical species niche models constructed for the British vascular plant and bryophyte flora. Key outcomes were (a) scored assessments of each modeled species and niche axis combination, (b) guidance on models needing further development, (c) exploration of the trade‐off between presenting more complex model summaries, which could lead to more thorough validation, versus the longer time these take to evaluate, (d) quantification of the internal consistency of expert opinion based on comparison of assessment scores made on a random subset of models evaluated by both experts. Overall, the experts assessed 39% of species and niche axis combinations to be “poor” and 61% to show a degree of reliability split between “moderate” (30%), “good” (25%), and “excellent” (6%). The two experts agreed in only 43% of cases, reaching greater consensus about poorer models and disagreeing most about models rated as better by either expert. This low agreement rate suggests that a greater number of experts is required to produce reliable assessments and to more fully understand the reasons underlying lack of consensus. While area under curve (AUC) statistics showed generally very good ability of the models to predict random hold‐out samples of the data, there was no correspondence between these and the scores given by the experts and no apparent correlation between AUC and species prevalence. Crowd‐sourcing further assessments by allowing web‐based access to model fits is an obvious next step. To this end, we developed an online application for inspecting and evaluating the fit of each niche surface to its training data. 相似文献
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Qi Tang Xian-Sheng Zhao Ao Guo Ruo-Tong Cui Huai-Le Song Zi-Yang Qi Yi Pan Yue Yang Fang-Fang Zhang Liang Jin 《World journal of stem cells》2022,14(10):744-755
Osteoarthritis (OA) is considered to be a highly heterogeneous disease with progressive cartilage loss, subchondral bone remodeling, and low-grade inflammation. It is one of the world's leading causes of disability. Most conventional clinical treatments for OA are palliative drugs, which cannot fundamentally cure this disease. The stromal vascular fraction (SVF) from adipose tissues is a heterogeneous cell population. According to previous studies, it contains a large number of mesenchymal stem cells, which have been used to treat OA with good therapeutic results. This safe, simple, and effective therapy is expected to be applied and promoted in the future. In this paper, the detailed pathogenesis, diagnosis, and current clinical treatments for OA are introduced. Then, clinical studies and the therapeutic mechanism of SVF for the treatment of OA are summarized. 相似文献
119.
《IRBM》2022,43(6):561-572
ObjectivesCerebrovascular disease is a serious threat to human health. Because of its high mortality and disability rate, early diagnosis and prevention are very important. The performance of existing cerebrovascular segmentation methods based on deep learning depends on the integrity of labels. However, manual labels are usually of low quality and poor connectivity at small blood vessels, which directly affects the cerebrovascular segmentation results.Material and methodIn this paper, we propose a new segmentation network to segment cerebral vessels from MRA images by using sparse labels. The long-distance dependence between vascular structures is captured by the global vascular context module, and the topology is constrained by the hybrid loss function to segment the cerebral vessels with good connectivity.ResultExperiments show that our method performed with a sensitivity, precision, dice similarity coefficient, intersection over union and centerline dice similarity coefficient of 61.24%, 75.58%, 67.66%, 51.13% and 83.79% respectively.ConclusionThe obtained results reveal that the proposed cerebrovascular segmentation network has better segmentation performance for cerebrovascular segmentation under sparse labels, and can suppress the noise of background to a certain extent. 相似文献
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