Carbon Nanotubes Promote the Development of Intestinal Organoids through Regulating Extracellular Matrix Viscoelasticity and Intracellular Energy Metabolism

ACS Nano ◽  
2021 ◽  
Author(s):  
Lin Bao ◽  
Xuejing Cui ◽  
Xiaoyu Wang ◽  
Junguang Wu ◽  
Mengyu Guo ◽  
...  
Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 6-8
Author(s):  
Takeshi Yamada ◽  
Yuya Arakawa

Adoptive immunotherapy can be used to treat intractable cancers but this involves taking T cells from a patient and growing them in a laboratory and, once outside the body, the T cells can fall into a state of exhaustion. This is a barrier that Professor Takeshi Yamada, Department of Medical Technology, Immunology, Ehime Prefectural University of Health Sciences, Japan, is seeking to overcome. His work involves establishing a better understanding of the mechanisms of T cell exhaustion, which are currently not well known. Yamada and his team are focusing on intracellular energy metabolism and epigenetic control in mouse models with a view to finding a way to inhibit T cell exhaustion. The researchers are developing protocols to improve T cell function for immunotherapy by controlling epigenetic changes involved in glutamine metabolism, which induces T cell exhaustion. As previous research has focused on activating and proliferating tumour-specific T cells, Yamada's approach, with a focus on epigenetic control, is novel. The team is interested in T cell differentiation and its links to T cell exhaustion and so they are exploring the mechanism of T cell differentiation via intracellular energy metabolism and epigenetic changes and how this can impact on exhaustion. The researchers previously clarified that the enhancement of glutamine metabolism that occurs during the activation of T cell cultures causes epigenetic changes that induce T cell exhaustion and are expanding on this finding in order to develop a method to suppress T cell exhaustion via epigenetic control.


1976 ◽  
Vol 101 (1) ◽  
pp. 47-54 ◽  
Author(s):  
E. Kohen ◽  
Cahide Kohen ◽  
B. Thorell

2020 ◽  
Vol 9 (8) ◽  
pp. 2070022
Author(s):  
Ella A. Hushka ◽  
F. Max Yavitt ◽  
Tobin E. Brown ◽  
Peter J. Dempsey ◽  
Kristi S. Anseth

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Liang Ji ◽  
Xiaoyu Guo ◽  
Jiachen Lv ◽  
Fan Xiao ◽  
Wangjun Zhang ◽  
...  

The present study was conducted to investigate the effect and potential mechanism of hypoxia-inducible factor-1α (HIF-1α) genetic inhibition plus glutamine (Gln) supplementation on necrosis-apoptosis imbalance during acute pancreatitis (AP), with a specific focus on the regulations of intracellular energy metabolism status. Wistar rats and AR42J cells were used to establish AP models. When indicated, a HIF-1α knockdown with or without a Gln supplementation was administered. In vivo, local and systemic inflammatory injuries were assessed by serum cytokine measurement, H&E staining, and transmission electron microscope (TEM) observation of pancreatic tissue. In vitro, intracellular energy metabolism status was evaluated by measuring the intracellular adenosine triphosphate (ATP), lactic acid, and Ca2+ concentrations and the mitochondrial potential. In addition, changes in the apoptotic activity were analyzed using TUNEL staining in vivo and an apoptosis assay in vitro. HIF-1α knockdown alleviated AP-related inflammatory injury as indicated by the measurements of serum cytokines and examinations of TEM and H&E staining of pancreatic tissues. HIF-1α knockdown played an antioxidative role against AP-related injuries by preventing the increase in the intracellular Ca2+ concentration and the decrease in the mitochondrial membrane potential and subsequently by suppressing the glycolysis pathway and increasing energy anabolism in AR42J cells after AP induction. Apoptosis was significantly upregulated when HIF-1α was knocked down before AP induction due to an attenuation of the translocation of nuclear factor-kappa B to the nuclei. Furthermore, these merits of HIF-1α knockdown in the relief of the metabolic stress and upregulation of apoptosis were more significant when Gln was administered concomitantly. In conclusion, Gln-supplemented HIF-1α knockdown might be promising for the future management of AP by relieving the intracellular energy stress, thereby attenuating the predominance of necrosis over apoptosis.


2020 ◽  
Vol 9 (8) ◽  
pp. 1901214 ◽  
Author(s):  
Ella A. Hushka ◽  
F. Max Yavitt ◽  
Tobin E. Brown ◽  
Peter J. Dempsey ◽  
Kristi S. Anseth

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rui Bai ◽  
Jianfeng Liu ◽  
Jiao Zhang ◽  
Jinmiao Shi ◽  
Zhigeng Jin ◽  
...  

Abstract Background The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair. Results In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair. Conclusions The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair. Graphic abstract


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