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931.
Rongkun Li Li Weng Bingyan Liu Lili Zhu Xiaoxin Zhang Guangang Tian Lipeng Hu Qing Li Shuheng Jiang Mingyi Shang 《Journal of cellular biochemistry》2020,121(2):1986-1997
Aberrant expression of the tripartite motif containing 59 (TRIM59) has been reported to participate in the development and progression of various human cancers. However, its expression pattern and cellular roles in pancreatic cancer (PC) remains unclear. In our study, we found that TRIM59 expression was significantly increased in PC tissues and was positively correlated with several malignant behaviors and poor overall survival of PC patients based on bioinformatics analysis and immunohistochemistry staining. Functionally, small interfering RNA–mediated TRIM59 depletion inhibited cell proliferation and migration in vitro, while TRIM59 overexpression promoted cell proliferation and migration in vitro and drove tumor growth and liver metastasis in vivo. Mechanically, TRIM59 was found to enhance glycolysis through activating the PI3K/AKT/mTOR pathway, ultimately contributing to PC progression. Taken together, our results demonstrate that TRIM59 may be a potential predictor for PC and promotes PC progression via the PI3K/AKT/mTOR-glycolysis signaling pathway, which establishes the rationale for targeting the TRIM59-related pathways to treat PC. 相似文献
932.
Gao Pan Gao Jingjing Dou Xianming Peng Dangwei Zhang Yao Li Hu Zhu Tianle Jiang Hui Zhang Xiansheng 《Molecular biology reports》2020,47(5):3605-3613
Molecular Biology Reports - This study is to explore the relationship between vascular endothelial growth factor (VEGF) and pathological changes in cryptorchidism by using murine model of... 相似文献
933.
Li-Min Lu Hai-Hua Hu Dan-Xiao Peng Bing Liu Jian-Fei Ye Tuo Yang Hong-Lei Li Miao Sun Stephen A. Smith Pamela S. Soltis Douglas E. Soltis Zhi-Duan Chen 《Journal of Biogeography》2020,47(10):2286-2291
In response to our paper on the evolutionary history of the Chinese flora, Qian suggests that certain features of the divergence time estimation employed might have led to biased conclusions in Lu et al (2018). Here, we consider Qian's specific criticisms, explore the extent of uncertainty in the data and demonstrate that (i) no systematic bias toward dates that are too young or too old is detected in Lu et al.; (ii) constraint of the crown age of angiosperms does not bias the generic ages estimated by Lu et al.; and (iii) ages derived from the Chinese regional phylogeny do not bias the conclusions reported by Lu et al. All these analyses confirm that the conclusions reported previously are robust. We argue that, like many large-scale biodiversity analyses, sources of noise in divergence time estimation are to be expected, but these should not be confused with bias. 相似文献
934.
Li Wanting Ye Anqi Ao Luyao Zhou Lin Yan Yunyi Hu Yahui Fang Weirong Li Yunman 《Neurochemical research》2020,45(10):2258-2277
Neurochemical Research - Stroke is the fifth leading cause of death worldwide and is a main cause of disability in adults. Neither currently marketed drugs nor commonly used treatments can promote... 相似文献
935.
936.
937.
Zhenghua Gong Jiayu Lin Jie Zheng Liya Wei Li Liu Yanzhong Peng Weicheng Liang Guoxin Hu 《Journal of cellular biochemistry》2020,121(2):1431-1440
It is well characterized that activated hepatic stellate cells (HSCs) exert critical functions in accelerating the progression of liver fibrosis. Previous studies have indicated that Dahuang Zhechong pill (DHZCP), a traditional Chinese herbal medicine, is capable of inactivating HSCs and thus attenuate the formation of liver fibrosis in rats. However, pharmacological mechanisms of DHZCP in alleviating liver fibrosis remain unclear. This study aims to investigate the antifibrotic role of DHZCP through inhibiting the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway. DHZCP was found to significantly suppresses extracellular matrix formation and immune cell infiltration, thus alleviating liver fibrosis symptoms in the in vivo model. Moreover, DHZCP reduced serum levels of transforming growth factor β1 and tumor necrosis factor-α in rats with liver fibrosis. DHZCP treatment remarkably downregulated protein levels of PI3K and phosphorylated Akt, as well as fibrosis markers. In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury. 相似文献
938.
939.
In this paper, we propose a Bayesian design framework for a biosimilars clinical program that entails conducting concurrent trials in multiple therapeutic indications to establish equivalent efficacy for a proposed biologic compared to a reference biologic in each indication to support approval of the proposed biologic as a biosimilar. Our method facilitates information borrowing across indications through the use of a multivariate normal correlated parameter prior (CPP), which is constructed from easily interpretable hyperparameters that represent direct statements about the equivalence hypotheses to be tested. The CPP accommodates different endpoints and data types across indications (eg, binary and continuous) and can, therefore, be used in a wide context of models without having to modify the data (eg, rescaling) to provide reasonable information-borrowing properties. We illustrate how one can evaluate the design using Bayesian versions of the type I error rate and power with the objective of determining the sample size required for each indication such that the design has high power to demonstrate equivalent efficacy in each indication, reasonably high power to demonstrate equivalent efficacy simultaneously in all indications (ie, globally), and reasonable type I error control from a Bayesian perspective. We illustrate the method with several examples, including designing biosimilars trials for follicular lymphoma and rheumatoid arthritis using binary and continuous endpoints, respectively. 相似文献