scholarly journals Microphysiological systems meet hiPSC technology – New tools for disease modeling of liver infections in basic research and drug development

2019 ◽  
Vol 140 ◽  
pp. 51-67 ◽  
Author(s):  
Martin Raasch ◽  
Enrico Fritsche ◽  
Andreas Kurtz ◽  
Michael Bauer ◽  
Alexander S. Mosig
Lab on a Chip ◽  
2017 ◽  
Vol 17 (18) ◽  
pp. 3026-3036 ◽  
Author(s):  
L. A. Low ◽  
D. A. Tagle

The high rate of failure during drug development is well-known, however recent advances in tissue engineering and microfabrication have contributed to the development of microphysiological systems (MPS), or ‘organs-on-chips’ that recapitulate the function of human organs.


2019 ◽  
Vol 15 (5) ◽  
pp. 472-485 ◽  
Author(s):  
Kuo-Chen Chou ◽  
Xiang Cheng ◽  
Xuan Xiao

<P>Background/Objective: Information of protein subcellular localization is crucially important for both basic research and drug development. With the explosive growth of protein sequences discovered in the post-genomic age, it is highly demanded to develop powerful bioinformatics tools for timely and effectively identifying their subcellular localization purely based on the sequence information alone. Recently, a predictor called “pLoc-mEuk” was developed for identifying the subcellular localization of eukaryotic proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems where many proteins, called “multiplex proteins”, may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mEuk was trained by an extremely skewed dataset where some subset was about 200 times the size of the other subsets. Accordingly, it cannot avoid the biased consequence caused by such an uneven training dataset. </P><P> Methods: To alleviate such bias, we have developed a new predictor called pLoc_bal-mEuk by quasi-balancing the training dataset. Cross-validation tests on exactly the same experimentconfirmed dataset have indicated that the proposed new predictor is remarkably superior to pLocmEuk, the existing state-of-the-art predictor in identifying the subcellular localization of eukaryotic proteins. It has not escaped our notice that the quasi-balancing treatment can also be used to deal with many other biological systems. </P><P> Results: To maximize the convenience for most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mEuk/. </P><P> Conclusion: It is anticipated that the pLoc_bal-Euk predictor holds very high potential to become a useful high throughput tool in identifying the subcellular localization of eukaryotic proteins, particularly for finding multi-target drugs that is currently a very hot trend trend in drug development.</P>


2018 ◽  
pp. 189-201
Author(s):  
Toshiyuki Araki ◽  
Masayoshi Kamon ◽  
Hidetoshi Sakurai

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 161
Author(s):  
Alexandra Gatzios ◽  
Matthias Rombaut ◽  
Karolien Buyl ◽  
Joery De Kock ◽  
Robim M. Rodrigues ◽  
...  

Although most same-stage non-alcoholic fatty liver disease (NAFLD) patients exhibit similar histologic sequelae, the underlying mechanisms appear to be highly heterogeneous. Therefore, it was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. As human-based in vitro research fulfils an irrefutable step in drug development, action should be taken as well in this stadium of the translational path. Indeed, most established in vitro NAFLD models rely on short-term exposure to fatty acids and use lipid accumulation as a phenotypic benchmark. This general approach to a seemingly ambiguous disease such as NAFLD therefore no longer seems applicable. Human-based in vitro models that accurately reflect distinct disease subgroups of MAFLD should thus be adopted in early preclinical disease modeling and drug testing. In this review article, we outline considerations for setting up translational in vitro experiments in the MAFLD era and allude to potential strategies to implement MAFLD heterogeneity into an in vitro setting so as to better align early drug development with future clinical trial designs.


2019 ◽  
Vol 117 ◽  
pp. 186-199 ◽  
Author(s):  
Huaying Chen ◽  
Zhihang Yu ◽  
Siwei Bai ◽  
Huaxiu Lu ◽  
Dong Xu ◽  
...  

2014 ◽  
Vol 14 (9) ◽  
pp. 1233-1240 ◽  
Author(s):  
Vinicius Rosa ◽  
Wei Seong Toh ◽  
Tong Cao ◽  
Winston Shim

2009 ◽  
Vol 69 (7) ◽  
pp. 2714-2719 ◽  
Author(s):  
Alan Serrels ◽  
Paul Timpson ◽  
Marta Canel ◽  
Juliane P. Schwarz ◽  
Neil O. Carragher ◽  
...  

2015 ◽  
Vol 7 (4) ◽  
pp. 383-391 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Michael L. Shuler

Advances in maintaining multiple human tissues on microfluidic platforms has led to a growing interest in the development of microphysiological systems for drug development studies.


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