EUROPEAN JOURNAL OF PHARMACOLOGY
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2018
·
IF 3.04
Qi Wan,Hui Chen,Xiaolei Li,Lianqi Yan,Yu Sun,Jingcheng Wang
Fibroblast proliferation is considered to be a major cause in the process of epidural fibrosis formation. Autophagy is a tightly-regulated catabolic process in charge of degrading intracellular components. Although autophagy has been associated with fibrosis of different tissues, the effect of autophagy on epidural fibrosis is still unknown. The aim of this study was to investigate the function and mechanism of autophagy induced by Artesunate (ART), a classical antimalarial agent extracted from the Chinese medicinal herb. In vitro, the effect of ART on inducing fibroblast autophagy was evaluated via LC3 immunofluorescent staining , Transmission Electron Microscopy (TEM) and western blotting analysis. Moreover, the effect of ART on inhibiting fibroblast proliferation was investigated by CCK-8 assay, EdU incorporation assay, flow cytometry and western blotting analysis. Results indicated that ART could induce autophagy and inhibit proliferation in fibroblasts. The inhibitory effect of ART on fibroblast proliferation was associated with the upregulation of p53 and p21 waf1/cip1 proteins. Intriguingly, 3-MA, a classical autophagy inhibitor, attenuated ART-induced p53/p21 waf1/cip1 pathway activation and fibroblast proliferation inhibition. In vivo, the effect of ART on reducing epidural fibrosis was detected by histological macroscopic assessment, hydroxyproline content analysis, histological and immunohistochemical staining. The results revealed that ART had significant suppressive effects on epidural fibrosis following laminectomy in rats. In conclusion, this research demonstrated that ART could inhibit fibroblast proliferation and reduce epidural fibrosis formation after laminectomy, and the potential mechanism might through autophagy cascade-mediated p53/p21 waf1/cip1 pathway. It might provide a novel reagent for reducing epidural fibrosis after spinal laminectomy surgery.
研究领域:
药理学
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神经外科
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Microbial Cell Factories
·
2021
·Vol. 20
·期 1
·1-12
·
IF 5.328
Jia Hexue,Sun Wan,Li Xuezhi,Zhao Jian
Background Trichoderma reesei is currently the main strain for the commercial production of cellulase. Cellulose induced protein 1 (Cip1) is one of the most abundant proteins in extracellular proteins of T. reesei. Reported literatures about Cip1 mainly focused on the regulation of Cip1 and its possible enzyme activities, but the effect of Cip1 on the enzymatic hydrolysis of lignocellulose and possible mechanism have not still been reported.Results In this study, Cip1 from T. reesei was cloned, expressed and purified, and its effects on enzymatic hydrolysis of several different pretreated lignocellulose were investigated. It was found that Cip1 could promote the enzymatic hydrolysis of pretreated lignocellulose, and the promoting effect was significantly better than that of bovine serum albumin (BSA). And especially for the lignocellulosic substrate with high lignin content such as liquid hot water pretreated corn stover and corncob residue, the promoting effect of Cip1 was even better than that of the commercial cellulase when adding equal amount protein. It was also showed that the metal ions Zn2+ and Cu2+ influenced the promoting effect on enzymatic hydrolysis. The Cip1 protein had no lyase activity, but it could destroy the crystal structure of cellulose and reduce the non-productive adsorption of cellulase on lignin, which partly interpreted the promoting effect of Cip1 on enzymatic hydrolysis of lignocellulose.Conclusion The Cip1 from T. reesei could significantly promote the enzymatic hydrolysis of pretreated lignocellulose, and the promotion of Cip1 was even higher than that of commercial cellulase in the enzymatic hydrolysis of the substrates with high lignin content. This study will help us to better optimize cellulase to improve its ability to degrade lignocellulose, thereby reducing the cost of enzymes required for enzymatic hydrolysis.
研究领域:
生物化学
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生物技术
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微生物学
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酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2025
·
IF 3.5
Zhen Yang,Feng Yan,Jiangwei Yuan,Manjun Yang,Jinyu Wang,Changqiao You,Kaiqun Ren
Background Cellular senescence refers to a condition where cells permanently cease division while maintaining metabolic activity. Doxorubicin (Dox) is known as an agent of induction of cellular senescence. This study aimed to explore the potential role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) in mitigating Dox induced senescent. Method NIH3T3 cells were treated by various concentrations of Dox with or without hucMSC-Exo, cell morphology, viability, migration, senescence-associated SA-β-Gal staining were monitored. Cellular senescence was induced in C57BL/6J mice via administration of 5 mg/kg Doxorubicin, followed by treatment with hucMSC-Exo or metformin. Assessments included body weight, liver and kidney weight, colon length, SA-β-Gal staining of kidney and skin, molecular biomarkers of aging such as p16 INK4A , p53, and p21 Waf1/Clip1 to evaluate senescence status. Result We found that after the treatment of exosomes or metformin improved several aging-related phenotypes in both mouse and cellular models, including increases in body weight, liver and kidney weights, and the reduction of SA-β-Gal positive cells in kidney and skin tissues as well as cell models. At the molecular level, hucMSC-Exo resulted in the downregulation of inflammatory factors and senescence markers in liver and kidney tissues as well as cell models. Conclusion Our study demonstrates hucMSC-Exo may ameliorate Dox induced senescence either in NIH3T3 cells or in mice.
研究领域:
干细胞研究
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药理学
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细胞生物学
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老年医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2021
·Vol. 35
·期 10
·e21923
·
IF 5.192
Peiling Wang,Xiangmei Hua,Yang Sun,Hongyu Li,Yuge Han Bryner,Richard P. Hsung,Jun Dai
Our recent studies have shown that haspin, a protein kinase imperative for mitosis, is engaged in the interphase progression of HeLa and U2OS cancer cells. In this investigation, we employed the Fucci reporter system and time-lapse imaging to examine the impact of haspin gene silencing on cell cycle progressions at a single-cell level. We found that the loss of haspin induced multiple cell cycle defects. Specifically, the S/G2 duration was greatly prolonged by haspin gene depletion or inhibition in synchronous HeLa cells. Haspin gene depletion in asynchronous HeLa and U2OS cells led to a similarly protracted S/G2 phase, followed by mitotic cell death or postmitotic G1 arrest. In addition, haspin deficiency resulted in robust induction of the p21 CIP1/WAF1 checkpoint protein, a target of the p53 activation. Also, co-depleting haspin with either p21 or p53 could rescue U2OS cells from postmitotic G1 arrest and partially restore their proliferation. These results substantiate the haspin's capacity to regulate interphase and mitotic progression, offering a broader antiproliferative potential of haspin loss in cancer cells.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）