scholarly journals Circular RNAs associated with a mouse model of concanavalin A‐induced autoimmune hepatitis: preliminary screening and comprehensive functional analysis

FEBS Open Bio ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2350-2362
Author(s):  
Yang Liu ◽  
Zhencheng Li ◽  
Jianheng Hao ◽  
Hao Chen ◽  
Tiezheng Hou ◽  
...  
Author(s):  
Jiawei Zhao ◽  
Yue Li ◽  
Rongrong Jia ◽  
Jinghui Wang ◽  
Min Shi ◽  
...  

Exosomes (Exos) are nanosized vesicles (around 100 nm) that recently serve as a promising drug carrier with high biocompatibility and low immunogenicity. Previous studies showed that Exos secreted from mesenchymal stem cells (MSCs) provide protection for concanavalin A (Con A)-induced liver injury. In this study, the protective effect of Exos is confirmed, and dexamethasone (DEX)-incorporated Exos named Exo@DEX are prepared. It is then investigated whether Exo@DEX can function more efficiently compared to free drugs and naive Exos in a Con A-induced autoimmune hepatitis (AIH) mouse model. The results show that Exo@DEX efficiently improves the accumulation of DEX in AIH in the liver. These data suggest that Exo@DEX is a promising drug carrier for AIH and could have applications in other diseases.


2019 ◽  
Vol 4 (5) ◽  
pp. 227–236
Author(s):  
WenQian Dong ◽  
Peng Luo ◽  
DaPeng Lu ◽  
Hao Wang ◽  
BaoLong Wang

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 597
Author(s):  
Artur Świerczek ◽  
Hanna Plutecka ◽  
Marietta Ślusarczyk ◽  
Grażyna Chłoń-Rzepa ◽  
Elżbieta Wyska

This study aimed to assess the efficacy and explore the mechanisms of action of a potent phosphodiesterase (PDE)7A and a moderate PDE4B inhibitor GRMS-55 in a mouse model of autoimmune hepatitis (AIH). The concentrations of GRMS-55 and relevant biomarkers were measured in the serum of BALB/c mice with concanavalin A (ConA)-induced hepatitis administered with GRMS-55 at two dose levels. A semi-mechanistic PK/PD/disease progression model describing the time courses of measured biomarkers was developed. The emetogenicity as a potential side effect of the studied compound was evaluated in the α2-adrenoceptor agonist-induced anesthesia model. The results indicate that liver damage observed in mice challenged with ConA was mainly mediated by TNF-α and IFN-γ. GRMS-55 decreased the levels of pro-inflammatory mediators and the transaminase activities in the serum of mice with AIH. The anti-inflammatory properties of GRMS-55, resulting mainly from PDE7A inhibition, led to a high hepatoprotective activity in mice with AIH, which was mediated by an inhibition of pro-inflammatory signaling. GRMS-55 did not induce the emetic-like behavior. The developed PK/PD/disease progression model may be used in future studies to assess the potency and explore the mechanisms of action of new investigational compounds for the treatment of AIH.


Hepatology ◽  
1985 ◽  
Vol 5 (5) ◽  
pp. 770-777 ◽  
Author(s):  
Teruo Mori ◽  
Yoshio Mori ◽  
Hiromichi Yoshida ◽  
Shiro Ueda ◽  
Makoto Ogawa ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiying Chen ◽  
Jiahui Wei ◽  
Min Li ◽  
Yongjuan Zhao

Abstract Background This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Methods The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed. Results A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. Conclusion Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.


2006 ◽  
Vol 44 ◽  
pp. S240
Author(s):  
K. Presser ◽  
K. Reifenberge ◽  
T. Bauer ◽  
T. Longerich ◽  
A. Quaas ◽  
...  

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