Cell Death & Disease
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2020
·Vol. 11
·期 5
·1-12
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IF 6.304
Ye Shuangyan,Xu Pengfei,Huang Mengqiu,Chen Xi,Zeng Sisi,Wang Qianli,Chen Jianping,Li Keyi,Gao Wenwen,Liu Ruiyuan,Liu Jingxian,Shao Yihao,Zhang Hui,Xu Yang,Zhang Qianbing,Zhong Zhuo,Wei Zibo,Wang Jiale,Hao Bingtao,Huang Wenhua,Liu Qiuzhen
Tempol (4-hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, TPL), a nitroxide compound, inhibits proliferation and increases the vulnerability of cancer cells to apoptosis induced by cytotoxic agents. However, the molecular mechanism of TPL inhibiting cancer cell proliferation has not been fully understood. In this study, we evaluated the metabolic effect of TPL on cancer cells and explored its cancer therapeutic potential. Extracellular flow assays showed that TPL inhibited cellular basal and maximal oxygen consumption rates of mitochondrial. 13 C metabolic flux analysis showed that TPL treatment had minimal effect on glycolysis. However, we found that TPL inhibits glutamine metabolism by interfering with the oxidative tricarboxylic acid cycle (TCA) process and reductive glutamine process. We found that the inhibitory effect of TPL on metabolism occurs mainly on the step from citrate to α-ketoglutarate or vice versa. We also found that activity of isocitrate dehydrogenase IDH1 and IDH2, the key enzymes in TCA, were inhibited by TPL treatment. In xenograft mouse model, TPL treatment reduced tumor growth by inhibiting cellular proliferation of xenograft tumors. Thus, we provided a mechanism of TPL inhibiting cancer cell proliferation by interfering with glutamine utilization that is important for survival and proliferation of cancer cells. The study may help the development of a therapeutic strategy of TPL combined with other anticancer medicines.
研究领域:
癌症生物学
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代谢生物学
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药理学
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PubMed
高影响因子
Bioactive Materials
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2022
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IF 16.874
Rui Wang,Jian Lu,Jiasheng Yin,Han Chen,Hongmei Liu,Fei Xu,Tongtong Zang,Rende Xu,Chenguang Li,Yizhe Wu,Qilin Wu,Xiang Fei,Meifang Zhu,Li Shen,Junbo Ge
An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.
研究领域:
生物医学工程
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药学
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心脏病学
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材料科学
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PubMed
高影响因子
Journal of Energy Storage
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2023
·
IF 9.4
Qinzheng Hu,Shuzhen Cui,Kanjun Sun,Xiuting Shi,Wenxing Miao,Xiangbing Wang,Hui Peng,Guofu Ma
In recent years, the research focus of flexible supercapacitor is to improve its energy density . The recently reported improved energy storage method is to introducing suitable redox-additive in gel electrolytes to enhance their redox-activity. Herein, a novel stretchable, redox-active and double-network 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxy-containing polyacrylamide/alginate/H 2 SO 4 (PAM/SA/H 2 SO 4 /TEMPOL) hydrogel electrolyte is prepared by radical cross-linking polymerization and solvent displacement process. The PAM/SA/H 2 SO 4 /TEMPOL hydrogel possesses superior stretchability (750 %) because of the electrostatic interactions between the -NH 3+ groups of the PAM and the -COO − groups of SA . In addition, the introduction of the TEMPOL additive into PAM/SA/H 2 SO 4 /TEMPOL hydrogel electrolyte of flexible EDLC can gain a high specific capacitance (386 F g −1 ) and high energy density of 24.5 Wh kg −1 , which is due to dual redox reactions both positive/negative electrode. This study provides a new strategy for designing a multifunctional redox hydrogel electrolyte.
研究领域:
材料科学
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电化学
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能源存储
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DOI
高影响因子
VETERINARY MICROBIOLOGY
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2026
·
IF 2.8
Leyu Hu,Lexi Gao,Xingwei Fu,Zesheng Rong,Yue Cheng,Yuhan Hou,Lu Han,Xin Ran,Guiwen Guan,Ting Zhou,Lingling Chang,Xiaomin Zhao,Qian Du,Yong Huang,Dewen Tong,Mingjun Zhu
PEDV infection induces intracellular iron accumulation in host cells. • Iron promotes CoV replication by enhancing Fe-S cluster-dependent RdRp activity. • TEMPOL suppresses CoV replication by disrupting viral Fe-S cluster integrity. • TEMPOL exhibits broad-spectrum anti-CoV activity in vitro and in vivo. • TEMPOL effectively counteracts iron-exacerbated viral pathogenesis in vivo. Coronaviruses (CoVs) can cause severe respiratory and enteric diseases, posing major threats to human health and the livestock industry. However, the host metabolic mechanisms underlying viral replication remain unclear. Using porcine epidemic diarrhea virus (PEDV) as the primary model, this study investigated the role of iron metabolism in CoV replication and its mechanisms. Our results showed that PEDV infection markedly induced intracellular iron accumulation, while exogenous iron supplementation enhanced viral replication and iron chelation suppressed it. Mechanistically, iron enhances viral replication by promoting the formation of iron-sulfur (Fe-S) clusters, essential cofactors for the viral RNA-dependent RNA polymerase (RdRp). Based on these findings, we further evaluated the antiviral activity of TEMPOL, a small molecule targeting viral Fe-S clusters. TEMPOL reduced RdRp activity and effectively inhibited PEDV replication. Moreover, TEMPOL exhibited broad-spectrum antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infectious bronchitis virus (IBV), and porcine deltacoronavirus (PDCoV). Importantly, TEMPOL effectively reversed FAC-promoted viral pathogenesis, alleviating tissue lesions and clinical symptoms across multiple CoV animal models. Collectively, this study reveals a key role of iron metabolism in CoV replication and suggests that targeting viral Fe-S clusters may provide a novel strategy for anti-CoV therapy against diverse CoVs.
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高影响因子
RSC Advances
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2023
·Vol. 13
·期 24
·16211-16221
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IF 3.9
Chunxiao Wang,Ruifu Zhao,Zhen Wang,Tingting Xu,Peng Huang
Atherosclerosis (AS), a chronic inflammatory disease, is the leading cause of death worldwide. Anti-oxidative therapy has been developed for AS therapy in light of the critical role of ROS in pathogenesis of AS, but current anti-oxidants have exhibited limited outcomes in the clinic. Herein, new ROS-eliminating liposome-like NPs (Tempol-Lips) were assembled from synthetic lipids that covalently conjugated two Tempol molecules with phosphatidylcholine by esterification reaction. The obtained Tempol-Lips can be efficiently internalized into inflammatory macrophages and attenuated inflammation via scavenging overproduced intracellular ROS. After i.v. administration, Tempol-Lips with nanoscale character accumulated in the plaques of ApoE−/− mice through passive targeting and significantly inhibited the pathogenesis of AS, compared with those treated with control drugs. The therapeutic benefits of Tempol-Lips primarily are ascribed to the reduced local and systematic oxidative stress and inflammation. Preliminary studies in vivo further demonstrated Tempol-Lips were safe and biocompatible after long-term i.v. injection. Conclusively, Tempol-Lips can be developed as a novel anti-AS nanotherapy with potential translation in the clinic.
研究领域:
心血管疾病
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纳米医学
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药学
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分子生物学
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PubMed
高影响因子
TOXICOLOGY LETTERS
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2019
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IF 3.499
Lingmin Zhang,Qingqing Xia,Yingying Zhou,Jie Li
Excessive accumulation of cadmium (Cd) in retina plays an important role in tobacco smoking-associated age-related macular degeneration (AMD). Plenty of evidence has revealed that the retinal pigment epithelium (RPE) is the primary site of pathology in AMD. Our current study demonstrated that Cd induced apoptosis in a human RPE cell line ARPE-19 cells, as it dose-dependently caused cell viability loss and activated caspase-3. The reactive oxygen species (ROS) were confirmed to be important mediators for Cd-triggered cell death in ARPE-19 cells. We found that endoplasmic reticulum (ER) stress was activated as its marker BiP was remarkably upregulated by Cd-exposure. Whereas the antioxidants N-acetylcysteine (NAC) and Tempol significantly suppressed the expression of BiP and CHOP, suggesting that ROS generation is an early trigger of Cd-activated ER stress. Furthermore, we found that Cd-induced oxidative stress significantly increased autophagic flux and p62 expression. A temporal impact of Cd exposure is possibly existed in p62 expression in ARPE-19 cells. Moreover, an ER stress inhibitor salubrinal diminished Cd-induced LC3BII expression and attenuated cytotoxicity, indicating that ER stress mediates autophagy and was implicated in apoptosis of Cd-exposed ARPE-19 cells. However, CHOP expression may not exert impact on the regulation of Cd-caused autophagy. Additionally, inhibition of autophagy with si-Beclin 1 and 3-Methyladenine significantly ameliorated Cd-induced CHOP expression and cytotoxicity, indicating that autophagy was detrimental in Cd-accumulated ARPE-19 cells, and a positive feedback regulation mechanism may exist between Cd-triggered ER stress and autophagy. Taken together, these results suggest that Cd-caused ER stress and autophagy are implicated in RPE cell death associated retinopathies especially related to smoking.
研究领域:
毒理学
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眼科学
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细胞生物学
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分子生物学
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高影响因子
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