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基于多组学探讨川陈皮素调控脂质合成氧化逆转胃癌顺铂耐药的机制
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作者 申隽于 李怀志 +5 位作者 陈梦麟 郑姗姗 张粲粲 韩博 吴坚 孙庆敏 《中草药》 CAS CSCD 北大核心 2023年第21期7066-7077,共12页
目的运用脂质代谢组学和网络药理学寻找川陈皮素对胃癌顺铂耐药细胞(AGS-DDP)的核心靶点,并结合细胞实验进一步探究川陈皮素逆转胃癌顺铂耐药的机制。方法采用UPLC-Orbitrap质谱系统进行非靶向脂质组学分析。利用GENE Card、TCMSP数据... 目的运用脂质代谢组学和网络药理学寻找川陈皮素对胃癌顺铂耐药细胞(AGS-DDP)的核心靶点,并结合细胞实验进一步探究川陈皮素逆转胃癌顺铂耐药的机制。方法采用UPLC-Orbitrap质谱系统进行非靶向脂质组学分析。利用GENE Card、TCMSP数据库挖掘川陈皮素和甘油磷脂代谢通路的潜在靶点,通过微生信在线作图工具平台整合二者的交集靶点,并进行基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,通过STRING数据库绘制蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,运用Cytoscape软件将川陈皮素的核心靶点可视化。川陈皮素给药后,通过CCK-8法检测AGS和AGS-DDP细胞的存活率;流式细胞术检测AGS-DDP细胞的凋亡情况;划痕实验检测AGS-DDP细胞的迁移能力;Western blotting检测AGS-DDP细胞的B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、E-cadherin、N-cadherin、Vimentin、过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptorγ,PPARγ)和三磷酸腺苷柠檬酸裂解酶(adenosine triphosphate citrate lyase,ACLY)蛋白表达。结果AGS和AGS-DDP细胞通过脂质组学分析检测得到31个亚类中的1450个差异的脂质化合物,主要富集在甘油磷脂代谢通路,对川陈皮素潜在靶点进行KEGG富集分析结果显示川陈皮素具有逆转铂类耐药的潜力。细胞实验结果显示,与对照组比较,川陈皮素剂量相关性地抑制AGS-DDP细胞的存活率(P<0.05、0.01),增加AGS-DDP细胞对顺铂的敏感性(P<0.05),且能诱导AGS-DDP细胞凋亡并抑制其迁移能力(P<0.05、0.01)。Western blotting实验结果显示川陈皮素组Bax、E-cadherin蛋白表达水平显著升高(P<0.05、0.01),Bcl-2、N-cadherin、Vimentin、ACLY和PPARγ蛋白表达水平均显著降低(P<0.05、0.01)。结论AGS和AGS-DDP细胞的差异脂质代谢产物主要富集在甘油磷脂代谢通路,川陈皮素通过调控脂质合成氧化关键基因抑制AGS-DDP细胞增殖、迁移,最终逆转胃癌顺铂耐药。 展开更多
关键词 胃癌 川陈皮素 网络药理学 顺铂耐药 脂质合成氧化 氧化物酶体增殖物激活受体Γ
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Use of Natural Antioxidants in Meat and Meat Products 被引量:8
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作者 M. Karakaya E. Bayrak K. Ulusoy 《Journal of Food Science and Engineering》 2011年第1期1-10,共10页
Antioxidants are used to minimize lipid oxidation. Antioxidants can act as metal chelators and free radical or oxygen scavengers, which can slow the progression of lipid oxidation. Lipid oxidation may have negative ef... Antioxidants are used to minimize lipid oxidation. Antioxidants can act as metal chelators and free radical or oxygen scavengers, which can slow the progression of lipid oxidation. Lipid oxidation may have negative effects on the quality of meat and meat products, causing changes in sensory attributes such as color, texture, odor and flavor, and nutritional quality. Several synthetic antioxidants have been used to successfully prevent lipid oxidation in the meat industry, but consumers are concerned about the health risks related to consumption of some synthetic antioxidants. Therefore, there has been a growing interest in natural antioxidants. Nowadays, compounds obtained from natural sources such as grains, oilseeds, spices, fruit and vegetables have been investigated to decrease the lipid oxidation. In this review, the potential effects of natural antioxidants were evaluated that are widely used in meat and meat products. 展开更多
关键词 Natural antioxidants HERBS SPICES TEAS FRUITS VEGETABLES meat products
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The Potential Application of Plant Essential Oils/Extracts as Natural Preservatives in Oils during Processing: A Review 被引量:1
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作者 Tugba lnanc Medeni Maskan 《Journal of Food Science and Engineering》 2012年第1期1-9,共9页
The present work summarizes recent investigations carried out about the usage of natural antioxidants in lipid-rich food during processing. Synthetic antioxidants have been used as food additives to retard lipid oxida... The present work summarizes recent investigations carried out about the usage of natural antioxidants in lipid-rich food during processing. Synthetic antioxidants have been used as food additives to retard lipid oxidation and development of off-flavor for over 50 years. However, the literature has expressed safety concerns and health risks (toxic and carcinogenic effects) associated with the use of synthetic antioxidants recently. Natural antioxidative substances from the polyphenols of edible plants are believed to be safer and may provide with additional health benefits and more effective compared to synthetic antioxidants. Due to the fact that natural antioxidants are additives that people mixed with food and consumed for centuries, they are known to be safe by the consumer. Therefore, it is an area worth to investigate due to consumer concerns about health. In the literature, there are many studies showing that the natural antioxidants have important antioxidant effect. Plants (oil seeds, cereals, vegetables, fruits, herb and spices), compounds from animal source (peptides and amino acids), enzymes and some microorganisms are important natural antioxidants. Plant extracts have been widely used to retard lipid oxidation in foods during frying and accelerated storage processes. They were found as strong antioxidant sources due to their high contents of phenolic compounds. There are countless studies about natural antioxidants. However, they have not been investigated completely by means of toxicology. 展开更多
关键词 FRYING OIL STORAGE stability natural antioxidants synthetic antioxidants.
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Dihydromyricetin improves liver fat deposition in high-fat diet-induced obese mice
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作者 Huijie Lv Tuo Xv +6 位作者 Jun Peng Gang Luo Jianqin He Sisi Yang Tiancheng Zhang Shuidong Feng Hongyan Ling 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2022年第11期824-839,共16页
It has been reported that the histone/protein deacetylase SIRT1-AMP-activated protein kinase(SIRT1-AMPK)signaling pathway may play a role in the effects of dihydromyricetin(DHM)on improving triglyceride(TG)accumulatio... It has been reported that the histone/protein deacetylase SIRT1-AMP-activated protein kinase(SIRT1-AMPK)signaling pathway may play a role in the effects of dihydromyricetin(DHM)on improving triglyceride(TG)accumulation and insulin resistance in liver cells.Therefore,we aimed to further observe the effect of DHM on liver fat deposition in high-fat diet(HFD)-induced obese mice and explore its possible mechanism.C57BL/6J mice were fed with a normal diet(ND)and HFD and were treated with or without low-dose(125 mg/kg)or high-dose(250 mg/kg)DHM for 16 weeks,respectively.During the experiment,body weight was checked every 2 weeks.After 16 weeks,the orbital vein was bled,the animals were sacrificed,and the subscapular,epididymal,and inguinal fat were collected and weighed with an electronic scale.An automatic biochemical analyzer was used to determine the levels of serum triglyceride(TG),serum total cholesterol(TC),serum high-density lipoprotein(HDL),and serum low-density lipoprotein(LDL).The livers were stained with hematoxylin-eosin staining(H&E)and Oil Red O to detect liver fat deposition.A colorimetric method was used to detect liver MDA and SOD contents.Quantitative real-time PCR(q RT-PCR)was used to detect the gene expressions of related indicators,such as interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),acetyl-Co A carboxyl acetyl-Co A carboxylase(ACC),sterol regulatory element-binding protein-1c(SREBP-1),fatty acid synthetase(FAS),peroxisome proliferator activation receptor alpha(peroxisome proliferator-activated receptor-alpha,PPARα),palmitoyltransferase 1(carnitine palmitoyltransferase 1,CPT1),SIRT1,and AMPK.Western blotting analysis was used to detect the protein expression levels of SIRT1,AMPK,SIRT1-AMPK,ACC,SREBP-1,FAS,PPARα,and CPT1.Results showed that compared with the ND group,the weight and body fat of the mice in the HFD group were increased significantly.The levels of TG,TC,and LDL were increased,the level of HDL was decreased,the volume of hepatocytes was increased,the number of lipid droplets,fat deposition,MDA,IL-6,IL-8,TNF-α,SREBP-1c,FAS,ACC1,SIRT1,and AMPK protein levels were significantly increased,and the SOD activity,PPARα,CPT1,SIRT1 m RNA,AMPK m RNA,PPARα,CPT1 levels were significantly decreased.DHM could significantly reverse the changes of the above indexes in HFD mice,while DHM had no significant effect on the above indexes in ND mice.Collectively,our findings revealed that DHM improved liver fat deposition in HFD-induced obese mice,and the mechanism might be related to inhibition of oxidative stress,inflammation,lipid synthesis,and promotion of lipid decomposition. 展开更多
关键词 DIHYDROMYRICETIN Obese mice Hepatic fat deposition Oxidative stress Inflammation Lipid synthesis Lipid breakdown
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