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Tetrandrine targeting SIRT5 exerts anti-melanoma properties via inducing ROS, ER stress, and blocked autophagy

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Journal of Pharmaceutical Analysis 2024年第10期14卷 1468-1483页

作者： Yacong Ji Chongyang Li Sicheng Wan Zhen Dong Chaolong Liu Leiyang Guo Shaomin Shi Mingxin Ci Minghao Xu Qian Li Huanrong Hu Hongjuan Cui Yaling Liu Department of Dermatology The Third Hospital of Hebei Medical UniversityShijiazhuang050051China State Key laboratory of Resource Insects Medical Research InstituteSouthwest UniversityChongqing400715China Department of medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai200433China JinFeng laboratory Chongqing400715China Engineering Research Center for Cancer Biomedical and Translational Medicine Southwest UniversityChongqing400715China

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra ***,has diverse pharmacological ***,its effects on melanoma remain *** prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on *** direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)*** findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)***,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma *** treatment resulted in excessive accumulation of reactive oxygen species(Ros)and simultaneously triggered *** 5(SIRT5)was ultimately found to be a direct target of ***,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome ***5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and ***,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 *** study highlights the potential of TET as an antimelanoma agent that targets *** findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

关键词： Melanoma Tetrandrine Sirtuin 5(SIRT5) Mitophagy Cytoskeletal protein depolymerization Reactive oxygen species(ROS)

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma

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Biomedical and Environmental Sciences 2019年第2期32卷 96-106页

作者： GAI Xiao Yan ZHANG Li Jiao CHANG Chun GUO Cheng Lin ABULIKEMU Mairipaiti LI Wen Xiong WANG Juan YAO Wan Zhen ZHANG Xu Department of Pulmonary and Critical Care Medicine Peking University Third Hospital Tianjin Key laboratory of Metabolic Diseases and Department of Physiology Tianjin Medical University

Objective To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. Methods Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ≥ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ≥ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. Results The serum lysophosphatidylglycerol level was significantly higher in the group with ≥ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ≥ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ≥ 71% and the group with sputum neutrophils < 71%. Conclusion Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

关键词： Eosinophilic asthma Neutrophilic asthma Glycerophospholipids Sputum induction Metabolomics

Wearable and interactive multicolored photochromic fiber display

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Light(Science & Applications) 2024年第3期13卷 454-465页

作者： Pan Li Yuwei Wang Xiaoxian He Yuyang Cui Jingyu Ouyang Ju Ouyang Zicheng He Jiayu Hu Xiaojuan Liu Hang Wei Yu Wang Xiaoling Lu Qian Ji Xinyuan Cai Li Liu Chong Hou Ning Zhou Shaowu Pan Xiangru Wang Huamin Zhou Cheng-Wei Qiu Yan-Qing Lu Guangming Tao State Key laboratory of Material Processing and Die&Mould Technology School of Materials Science and Engineering and Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan 430074China Key laboratory of Vascular Aging(HUST) Ministry of EducationWuhan 430030China School of Optoelectronic Science and Engineering University of Electronic Science and Technology of ChinaChengdu 611731China Department of Electrical and Computer Engineering National University of SingaporeSingapore 117583Singapore National laboratory of Solid State Microstructures Key Laboratory of Intelligent Optical Sensing and ManipulationCollege of Engineering and Applied Sciencesand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210023China School of Performing Arts Wuhan Conservatory of MusicWuhan 430060China School of Mechanical Science and Engineering Huazhong University of Science and TechnologyWuhan 430074China School of Architecture and Urban Planning Huazhong University of Science and TechnologyWuhan 430074China School of Fashion Beijing Institute of Fashion TechnologyBeijing 100029China School of optical and Electronic Information Huazhong University of Science and TechnologyWuhan 430074China Tongji medical College Huazhong University of Science and TechnologyWuhan 430074China State Key laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai 201620China

Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent,wearable interactive ***,significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight ***,we introduce a mass-produced,wearable,and interactive photochromic fiber that provides uniform multicolored light *** designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the *** impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission *** addition,we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single *** prepared fibers on mass-produced kilometer-long using the thermal drawing *** fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as *** work provides a new perspective and inspiration to the existing field of fiber display interaction,paving the way for future human–machine integration.

关键词： fiber interactive colored

Characterization of Acidic Glycosphingolipid Changes in C6 Glioma Rats Treated With Temozolomide Using Ultra-High-Performance Liquid Chromatography Coupled With Quadrupole Time-of-Flight mass spectrometry

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Journal of Analysis and Testing 2020年第3期4卷 217-225页

作者： Tian-Kun Ren Meng-Lin Li Hao Zheng Zhe Wang Jin-Lan Zhang State Key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050People’s Republic of China

Ganglioside and sulfatide are primary components of acidic glycosphingolipids(AGSLs),which are abundant in the brain *** are potential tumor *** this paper,we use ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry to generate a first-ever comprehensive profile of AGSLs in brain and plasma of C6 glioma rats treated with temozolomide(TMZ).The AGSLs detected consisted mainly of C18-/C20-sphingosine.12,20,19,14 and 12 species were identified in GM1,GD1a,GD1b,GM3 and GT1b ganglioside groups which were abundant in rat brain,*** five groups accounted for 88-89%of total ganglioside ***,no AGSLs were detected in rat *** biomarkers for abnormal changes in the glioma model and the protective effect of TMZ were mainly found in these ganglioside groups and *** main lipid component of central and peripheral nervous system myelin sheathes is sulfatide,which is upregulated in many *** properties of TMZ are due to modulation of sulfatide levels in tumor tissues.

关键词： Acidic glycosphingolipids Temozolomide C6 glioma UPLC-QTOF-MS

Serum vitamin D_3 does not correlate with liver fibrosis in chronic hepatitis C

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World Journal of Gastroenterology 2015年第39期21卷 11152-11159页

作者： Yan Ren Mei Liu Jing Zhao Feng Ren Yu Chen Jun-Feng Li Jing-Yun Zhang Feng Qu Jin-Lan Zhang Zhong-Ping Duan Su-Jun Zheng Artificial Liver Center Beijing You An Hospital Capital Medical University Institute of Liver Diseases Beijing YouA n Hospital Capital Medical University State Key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

AIM: To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C(CHC).METHODS: From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxicity, Gansu Province, China. The patients were infected with Hepatitis C virus(HCV) during blood cell retransfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholineste rase, prothrom binactivity, albumin, γ-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry.R E S U LT S : Serumlevels of 2 5(OH) D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation ***: We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chi

关键词： Hepatitis C virus 25-Hydroxyvitamin D3 24,25-Dihyd

Yemazhui(Herba Eupatorii Lindleyani)ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flor

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Journal of Traditional Chinese Medicine 2024年第2期44卷 303-314页

作者： REN Li HAI Yang YANG Xue LUO Xianqin Chongqing Key laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases College of Traditional Chinese MedicineChongqing Medical UniversityChongqing 400016China College of Basic Medicine Chongqing Medical UniversityChongqing 400016China

OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in ***:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry ***,HEL was found to suppress LPS-induced ALI in ***-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)*** model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI *** counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and ***,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal ***:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora *** study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung *** addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturban

关键词： Yemazhui(Herba Eupatorii Lindleyani) acute lung injury anti-inflammation toll-like receptor 4 nuclear factor kappa-B nod-like receptor family pyrin domain-containing 3 protein signal transduction gastrointestinal microbiome

Protein expression profile in the differentiation of rat bone marrow stromal cells into Schwann cell-like cells

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Science China(Life Sciences) 2009年第3期52卷 267-277页

作者： LI WenTing1,SUN HuaLin2,XU ZengLu1,DING Fei2 & GU XiaoSong2 1 Department of Anatomy,Histology and Embryology,Peking Union medical College,Institute of Basic medical Science,Chinese Academy of medical Sciences,Beijing 100005,China 2 Jiangsu Key laboratory of Neuroregeneration,Nantong University,Nantong 226001,China 1. Department of Anatomy Histology and Embryology Peking Union Medical College Institute of Basic Medical Science Chinese Academy of Medical Sciences Beijing 100005 China 2. Jiangsu Key laboratory of Neuroregeneration Nantong University Nantong 226001 China

During the last decade,increasing evidence suggested that bone marrow stromal cells(MSCs) have the potential to differentiate into neural *** studies have reported that MSCs showed morphological changes and expressed a limited number of neural proteins under experimental ***,no proteomic studies on MSCs differentiated into Schwann cell-like cells have been *** this study,we isolated MSCs from adult Sprague-Dawley rat femur and tibia bone marrows and induced the cells in vitro under specific *** using two-dimensional gel electrophoresis(2-DE),we compared the protein profiles of MSCs before and after induced *** obtained 792 protein spots in the protein profile by 2-DE,and found that 74 spots changed significantly before and after the differentiation using PDQuest software,with 43 up-regulated and 31 *** analyzed these 74 spots by a matrix assisted laser desorption ionization-time of flight mass spectrometry(MALDI-TOF-MS) and by database searching,and found that they could be grouped into various classes,including cytoskeleton and structure proteins,growth factors,metabolic proteins,chaperone proteins,receptor proteins,cell cycle proteins,calcium binding proteins,and other *** proteins also include neural and glial proteins,such as BDNF,CNTF and *** results may provide valuable proteomic information about the differentiation of MSCs into Schwann cell-like cells.

关键词： one marrow stromal cells(MSCs) differentiation Schwann cell-like cells proteomics

Association of altered serum acylcarnitine levels in early pregnancy and risk of gestational diabetes mellitus

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Science China Chemistry 2020年第1期63卷 126-134页

作者： Hongzhi Zhao Han Li Yuanyuan Zheng Lin Zhu Jing Fang Li Xiang Shunqing Xu Yanqiu Zhou Hemi Luan Wei Xia Zongwei Cai State Key laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong KongChina Key laboratory of Environment and Health Ministry of Education&Ministry of Environmental ProtectionState Key Laboratory of Environmental Health(Incubation)School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430074China

Gestational diabetes mellitus(GDM)is a high-prevalence disease and diagnosed in middle *** are a series of fatty acid esters of carnitine and play important roles in fatty acid and carbohydrate ***,the role of acylcarnitine on the development of GDM remains *** case-control study involving 214 study participants(107 GDM cases and 107 matched controls)was conducted in a cohort,in China,from 2013 to *** levels of carnitine and 36 acylcarnitines in serum samples collected at the early stage of pregnancy were determined by using ultra-high performance liquid chromatography coupled with tandem mass *** associations of the levels of the 37 targeted compounds with GDM risk were investigated by using binary conditional logistic regression *** in acylcarnitine levels were observed 9–17 weeks before GDM *** increases in levels of propionyl-carnitine,malonyl-carnitine,isovaleryl-carnitine,palmitoyl-carnitine and linoleoyl-carnitine were associated with GDM risk with odds ratios(ORs)per standard deviation(SD)increment greater than 1(pmass index and parity).On the contrary,the increases of decanoyl-carnitine,decenoyl-carnitine,tetradecenoyl-carnitine,tetradecandienoylcarnitine levels were associated with the reduced risk for GDM(ORs per SD<1,p<0.05).To our knowledge,the present study is the largest case-control study to investigate the association between early-pregnancy acylcarnitine levels in serum and GDM *** findings add to the evidence for the association between acylcarnitine levels and GDM risk.

关键词： acylcarnitines gestational diabetes mellitus epidemiology targeted metabolomics ultra-high performance liquid chromatography coupled with tandem mass spectrometry

The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

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Genes & Diseases 2024年第3期11卷 452-467页

作者： Min Wang Yixue Gu Qiubo Li Bangzhe Feng Xinke Lv Hao Zhang Qingxia Kong Zhifang Dong Xin Tian Yanke Zhang Department of Neurology Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China Department of Pediatrics Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Neurosurgery Affliated Hospital of Jining Medical UniversityJiningShandong 272000China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent *** lobe epilepsy(TLE)is one of the most common medically intractable seizure ***2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains *** this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of ***(Co-IP)/mass spectrometry(MS)was used to identify the potential *** Co-IP,we detected and confirmed the main potential TNIK *** fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)*** found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with ***-0846 delayed kindling progression and decreased seizure ***-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably ***-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and *** addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ *** results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

关键词： Epilepsy NCB-0846 Rat TLE TNIK Traf2-and NcK-interacting kinase