EUROPEAN JOURNAL OF PHARMACOLOGY
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2022
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IF 5.195
Ying Wang,Qiong Cheng,Qina Su,Xuesong Yu,Tianqi Shen,Xiaoling Yang,Weizhang Jia
Aesculin , a coumarin compound, is one of the major active ingredients of traditional Chinese herbal medicine Qinpi (Cortex Fraxini), which has been reported to exhibit antioxidative, anti-inflammatory and neuroprotective properties against oxidative stress and cellular apoptosis . However, the regulatory mechanisms remain poorly characterized in vivo . This research was performed to explore the underlying molecular mechanisms behind aesculin response conferring oxidative stress resistance, and the protective effects on amyloid-β (Aβ)-mediated neurotoxicity in Caenorhabditis elegans . Study indicated that aesculin plays the protective roles for C. elegans against oxidative stress and Aβ-mediated neurotoxicity and reduces the elevated ROS and MDA contents through enhancement of antioxidant defenses. The KEGG pathway analysis suggested that the differentially expressed genes are mainly involved in longevity regulating pathway, and the nuclear translocation of DAF-16 and the RNAi of daf-16 and hsf-1 indicated that DAF-16 and HSF-1 play critical roles in integrating upstream signals and inducing the expressions of stress resistance-related genes. Furthermore, the up-regulated expressions of their target genes such as sod-3 and hsp-16.2 were confirmed in transgenic GFP reporter strains CF1553 and CL2070, respectively. These results indicated that the regulators DAF-16 and HSF-1 elevate the stress resistance of C. elegans by modulating stress-responsive genes. Further experiments revealed that aesculin is capable of suppressing Aβ-induced oxidative stress and apoptosis and improves chemosensory behavior dysfunction in Aβ-transgenic nematodes. In summary, this study suggested that aesculin offers increased resistance against oxidative stress and protective effects against Aβ-induced neurotoxicity through activation of stress regulators DAF-16 and HSF-1 in nematodes .
研究领域:
分子生物学
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神经科学
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药理学
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遗传学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
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2021
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IF 5.75
Bai Shuju,Wang Wenbo,Zhang Zhiwei,Li Mengyao,Chen Zehan,Wang Jiuqiao,Zhao Yanlin,An Lu,Wang Yuxiang,Xing Shu,Fu Xueqi,Ma Junfeng
Amyloid-β, a hallmark of Alzheimer’s disease, forms toxic intracellular oligomers and extracellular senile plaques resulting in neuronal toxicity. Ethanol is widely consumed worldwide. Moderate ethanol consumption has numerous benefits in humans. We found that ethanol could significantly extend the lifespan of Caenorhabiditis elegans in a previous study. Based on that study, we tested the effect of ethanol on Alzheimer’s disease transgenic Caenorhabiditis elegans strain CL4176, which expresses amyloid-β1-42 peptide in body wall muscle cells. Ethanol delayed paralysis and reduced amyloid-β oligomers in Caenorhabiditis elegans worms of the CL4176 strain. Moreover, ethanol could induce the nuclear translocation of DAF-16 in the nematodes. However, in worms that were fed daf-16 RNAi bacteria, ethanol no longer delayed the paralysis. The qPCR assays showed that ethanol increases the expression of daf-16, hsf-1 and their common target genes- small heat shock protein genes. In addition, we also found that ethanol could increase lysosome mass in the CL4176 worms. In summary, our study indicated that ethanol attenuated amyloid-β toxicity in the Alzheimer’s disease model of Caenorhabiditis elegans via increasing the level of lysosomes to promote amyloid-β degradation and upregulating the levels of small heat shock protein genes to reduce amyloid-β aggregation.
研究领域:
神经科学
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分子生物学
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衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Huamei He,Lanlan Liu,Shengping Zhang,Mingbin Zheng,Aiqing Ma,Ze Chen,Hong Pan,Haimei Zhou,Ruijing Liang,Lintao Cai
Chemotherapy is an important modality available for cancer treatment. However, the present chemotherapy is still far from being satisfactory mainly owing to the severe side effects of the chemotherapeutic agents and drug resistance of cancer cells. Thus, reversing drug resistance by constructing an ideal chemotherapeutic strategy with the least side effects and the best efficacy is greatly needed. Here, we designed a smart nanosystem of thermo-sensitive liposome coated gold nanocages with doxorubicin (DOX) loading (LAD) for near-infrared (NIR)-triggered drug release and chemo-photothermal combination therapy. The biocompatible liposomes coating facilitated the cellular uptake of LAD and meanwhile avoided drug leakage during the circulation. More importantly, LAD exhibited controllable photothermal conversion property and produced mild heat under NIR irradiation, which not only triggered DOX release and transferred DOX from lysosome to nucleus, but also elicited the mild heat cell killing effect to improve the curative efficiency. Further mechanism study revealed that mild heat could reverse drug resistance by down-regulation of the chemoresistance-related markers ( e.g. , HSF-1, p53, P-gp), and inhibited DOX export and increased drug sensitiveness, thereby prominently increased the anticancer efficiency. This versatile nanoplatform with enhanced curative efficacy and lower side effect is promising to apply in the field of drug controlled release and combination tumor therapy.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Qianzi Chen,Xuekui Nie,Wangxiang Huang,Chen Wang,Ren Lai,Qiumin Lu,Qiyi He,Xiaodong Yu
Chicken meat processing generates a substantial number of byproducts, which are either underutilized or improperly disposed. In this study, we employed in silico approaches to identify antioxidant peptides in chicken liver byproducts. Notably, the peptide WYR exhibited remarkable 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity with an IC 50 of 0.13 ± 0.01 mg/mL and demonstrated stability under various conditions, including thermal, pH, NaCl, and simulated gastrointestinal digestion. Molecular docking analysis revealed significant hydrogen bonding interactions, while molecular dynamics showed differential stability with ABTS and 2,2-Diphenyl-1-picrylhydrazyl (DPPH). WYR exhibited improved stress resistance, decreased levels of reactive oxygen species (ROS), elevated the activities of superoxide dismutase (SOD) and catalase (CAT), and modulated the expression of crucial genes through the insulin/insulin-like growth factor (IIS) signaling pathway, mitogen-activated protein kinase (MAPK), and heat shock transcription factor-1 (HSF-1) pathways. These effects collectively contributed to the extension of Caenorhabditis elegans ' lifespan. This study not only provides an effective method for antioxidant peptide analysis but also highlights the potential for enhancing the utilization of poultry byproducts.
研究领域:
食品科学
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生物技术
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分子生物学
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衰老研究
✓ 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）