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| 1 | Melatonin enhances radiofrequency-induced NK antitumor immunity,causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development显示文摘Surgery is the comm on treatme nt for early lung cancer with multiple pulm onary no dules,but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas.In this study,we found that a combined treatment of local rad iofreq ue ncy ablati on(RFA)and melatonin(MLT)greatly improved clinical outcomes for early lung cancer patie nts with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas.Mechanically,as demonstrated in an associated mouse lung tumor model,RFA not only effectively remove treated tumors but also stimulate antitumor immunity,which could inhibit tumor growth in non-ablated areas.MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA.Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment,which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT.Analysis of residual tumor further revealed the depressed activity of MAPK,NF-kappa B,Wnt,and Hedgehog pathways and upregulated P53 pathway in tumors,which was in line with the inhibited tumor growth.Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy.These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules.Trial registration:www.chictr.org.cn,identifier ChiCTR2100042695,http://gffzz62a03ee25e6f4a77hn9fokqx50nxp690c.ffgz.tsg.suse.edu.cn/showproj.aspx?proj=120931. | Ming Li Bingjie Hao Menghuan Zhang Russel J.Reiter Shumeng Lin Tiansheng Zheng Xiangyun Chen Yanbei Ren Liduo Yue Baigenzhin Abay Guojie Chen Xiao Xu Yufeng Shi Lihong Fan | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 6 |
| 2 | Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis显示文摘 | Lin He Xinhua Liu Jianguo Yang Wanjin Li Shumeng Liu Xujun Liu Ziran Yang Jie Ren Yue Wang Lin Shan Chengjian Guan Fei Pei Liandi Lei Yu Zhang Xia Yi Xiaohan Yang Jing Liang Rong Liu Luyang Sun Yongfeng Shang | 2018 | Cell Research2018，28，9： | 5 |
| 3 | The existence of a nonclassical TCA cycle in the nucleus that wires the metabolic-epigenetic circuitry显示文摘The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid(TCA)cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus.We report here the identification of a nonclassical TCA cycle in the nucleus(nTCA cycle).We found that all the TCA cycle-associated enzymes including citrate synthase(CS),aconitase 2(ACO2),isocitrate dehydrogenase 3(IDH3),oxoglutarate dehydrogenase(OGDH),succinyl-CoA synthetase(SCS),fumarate hydratase(FH),and malate dehydrogenase 2(MDH2),except for succinate dehydrogenase(SDH),a component of electron transport chain for generating ATP,exist in the nucleus.We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria.We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates,not for energy production.We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation.Together,our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation. | Xujun Liu Wenzhe Si Lin He Jianguo Yang Yani Peng Jie Ren Xiaoping Liu Tong Jin Huajing Yu Zihan Zhang Xiao Cheng Wenting Zhang Lu Xia Yunchao Huang Yue Wang Shumeng Liu Lin Shan Yu Zhang Xiaohan Yang Haixia Li Jing Liang Luyang Sun Yongfeng Shang | 2021 | Signal Transduction and Targeted Therapy2021，6，12： | 0 |
| 4 | Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection显示文摘Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities.Methods: The AlCl3colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti-oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18column(2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase(PDB ID: 2CDU) by molecular docking.Results: Combined with the results of activity screening in vitro, the anti-oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatographymass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile.Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin. | Xiajing Xu Yongli Guo Menglin Chen Ning Li Yi Sun Shumeng Ren Jiao Xiao Dongmei Wang Xiaoqiu Liu Yingni Pan | 2024 | Chinese Herbal Medicines2024，16，1： | 0 |
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