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Tai, Yu-Tzu,Chang, Betty Y.,Kong, Sun-Young,Fulciniti, Mariateresa,Yang, Guang,Calle, Yolanda,Hu, Yiguo,Lin, Jianhong,Zhao, Jian-Jun,Cagnetta, Antonia,Cea, Michele,Sellitto, Michael A.,Zhong, Mike Y. American Society of Hematology 2012 Blood Vol.120 No.9
<B>Abstract</B><P>Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, whereas its expression in osteoclasts (OCs) further suggests a role in osteoclastogenesis. Here we investigated effects of PCI-32765, an oral and selective Btk inhibitor, on osteoclastogenesis as well as on multiple myeloma (MM) growth within the BM microenvironment. PCI-32765 blocked RANKL/M-CSF-induced phosphorylation of Btk and downstream PLC-γ2 in OCs, resulting in diminished TRAP5b (ED50 = 17nM) and bone resorption activity. PCI-32765 also inhibited secretion of multiple cytokines and chemokines from OC and BM stromal cell cultures from both normal donors (ED50 = 0.5nM) and MM patients. It decreased SDF-1-induced migration of MM cells, and down-regulated MIP1-α/CCL3 in MM cells. It also blocked MM cell growth and survival triggered by IL-6 or coculture with BM stromal cells or OCs in vitro. Importantly, PCI-32765 treatment significantly inhibits in vivo MM cell growth (P < .03) and MM cell-induced osteolysis of implanted human bone chips in SCID mice. Moreover, PCI-32765 prevents in vitro colony formation by stem-like cells from MM patients. Together, these results delineate functional sequelae of Btk activation mediating osteolysis and growth of MM cells, supporting evaluation of PCI-32765 as a novel therapeutic in MM.</P>
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Comparative Study of Two Common In Vitro Models for the Pancreatic Islet with MIN6
Chao Xinxin,Zhao Furong,Hu Jiawei,Yu Yanrong,Xie Renjian,Zhong Jianing,Huang Miao,Zeng Tai,Yang Hui,Luo Dan,Peng Weijie 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.1
BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION: This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.
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De-Jun Cheng,Jie Zhang,Zhong-Tai Hu,Sheng-Hao Xu,Xi-Feng Fang 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.10
This paper aims to propose a digital twin-driven (DTD) approach that consists of the machining data (MD) in twin data (TD), design of MD acquisition methodology, construction of intelligent algorithm, real-virtual data interaction analysis and fusion technology, which improvs the predictability and management of on-line quality control of marine diesel engine (MDE) critical parts. Firstly, this paper introduces the theoretical framework of DTD on-line quality control in machining process. Secondly, we construct the process of DTD on-line quality control and introduce the digital twin model of on-line quality control based on TD-driven; the operation of data-driven quality on-line control based on digital twin including description and modeling of MD; acquisition of MD based on digital twin; TD-driven on-line tool life prediction and data fusion on-line machining parameters optimization methods. Finally, a case study is applied to validate the accuracy and availability of the DTD approach. The proposed approach provides a new way for the on-line quality control of MDE critical parts in machining process.
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