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Apple polyphenol phloretin inhibits type II glucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer

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Food science and Human Wellness 2024年

作者： Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Pei-Han Liao Yu-Ching Lee Chi-Tang Ho Min-Hsiung Pan Li-Ching Chen Yuan-Soon Ho department of Biological science & Technology， College of Life sciences， China Medical university Institute of biochemistry and molecular biology， College of Life sciences， China Medical university department of Surgery， School of Medicine， College of Medicine， Taipei Medical university Research center of Cancer Translational Medicine， Taipei Medical university department of Food science， Rutgers university New Jersey， USA Institute of Food sciences and Technology， Taiwan university

This study presents novel findings on the potential of phloretin， an apple polyphenol， to enhance the effectiveness of anti-HER2 antibody therapy in HER2-positive breast cancer patients. Our research reveals that phloretin inhibits type II glucose transporter (GLUT2) activity， significantly reducing cancer cell glucose uptake. We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues， with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients. Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins， attenuate glycolysis， and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells. Furthermore， the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft (CDX) tumor animal model， particularly in suppressing the growth of Trastuzumab-resistant HER2+ breast cancer. These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer， offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.

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Stay in touch with the endoplasmic reticulum

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science China(Life sciences) 2024年第2期67卷 230-257页

作者： Sha Sun Gan Zhao Mingkang Jia Qing Jiang Shulin Li Haibin Wang Wenjing Li Yunyun Wang Xin Bian Yan G.Zhao Xun Huang Ge Yang Huaqing Cai Jose C.Pastor-Pareja Liang Ge Chuanmao Zhang Junjie Hu National Laboratory of Biomacromolecules Institute of BiophysicsUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking UniversityBeijing 100871China State Key Laboratory of Membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Laboratory of Computational biology&Machine Intelligence School of Artificial IntelligenceUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Medicinal Chemical biology College of Life SciencesNankai UniversityTianjin 300071China Brain Research center Department of BiologySchool of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China State Key Laboratory of molecular Developmental biology Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Institute of Neurosciences Consejo Superior de Investigaciones Científicas-Universidad Miguel HernándezSan Juan de Alicante 03550Spain

The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic *** a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling ***,we systematically review recent advances and converging themes on ER-involved organellar *** molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.

关键词： endoplasmic reticulum nuclear envelope mitochondria Golgi apparatus endosome lysosome lipid droplets autophagosome plasma membrane membrane contact site

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

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Signal Transduction and Targeted Therapy 2024年第1期9卷 105-149页

作者： Yumin Wang Jing Hu Shuang Wu Joshua S.Fleishman Yulin Li Yinshi Xu Wailong Zou Jinhua Wang Yukuan Feng Jichao Chen Hongquan Wang department of Respiratory and Critical Care Medicine Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China department of Pathogen biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300060PR China department of Neurology Zhongnan Hospital of Wuhan UniversityWuhan 430000PR China department of Pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA department of Outpatient Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050PR China department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060PR China

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug *** epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and *** studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney *** this review,we first summarize the core molecular mechanisms of ***,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely *** roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in *** the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other *** addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

关键词： diseases epigenetic overcome

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High-Efficiency Photo-Induced Charge Transfer for SERS Sensing in N-Doped 3D-Graphene on Si Heterojunction

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Energy & Environmental Materials 2024年第2期7卷 268-276页

作者： Guanglin Zhang Jie Sun Genwang Wei Shan Zhang Zhengyi He Huijuan Wu Bingkun Wang Siwei Yang Guqiao Ding Zhiduo Liu Zhiwen Jin Caichao Ye Gang Wang department of Microelectronic science and Engineering School of Physical Science and TechnologyNingbo UniversityNingbo 315211China department of biochemistry and molecular biology School of Basic Medical SciencesShenzhen UniversityShenzhen 518071China Academy for Advanced Interdisciplinary Studies&department of Materials science and Engineering Guangdong Provincial Key Laboratory of Computational Science and Material DesignSouthern University of Science and TechnologyShenzhen 518055China State Key Laboratory of Functional Materials for Informatics Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050China Centre for Quantum Physics Key Laboratory of Advanced Optoelectronic Quantum Architecture and Measurement(MOE)School of PhysicsBeijing Institute of TechnologyBeijing 100081China School of Physical science and Technology&Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education Lanzhou UniversityLanzhou 730000China

Nitrogen-doped three-dimensional graphene(N-doped 3D-graphene)is a graphene derivative with excellent adsorption capacity,large specific surface area,high porosity,and optoelectronic ***,N-doped 3D-graphene/Si heterojunctions were grown in situ directly on silicon(Si)substrates via plasma-assisted chemical vapor deposition(PACVD),which is promising for surface-enhanced Raman scattering(SERS)substrates *** analyses of theoretical simulation,incorporating N atoms in 3D-graphene are beneficial to increase the electronic state density of the system and enhance the charge transfer between the substrate and the target *** enhancement of the optical and electric fields benefits from the stronger light-matter interaction improved by the natural nano-resonator structure of N-doped *** as-prepared SERS substrates based on N-doped 3D-graphene/Si heterojunctions achieve ultra-low detection for various molecules:10^(-8)M for methylene blue(MB)and 10^(-9)M for crystal violet(CRV)with rhodamine(R6G)of 10^(10)*** practical detected,10^(-8)M thiram was precisely detected in apple peel *** results indicate that N-doped 3D-graphene/Si heterojunctions based-SERS substrates have promising applications in low-concentration molecular detection and food safety.

关键词： charge transfer DFT simulation N-doped 3D-graphene SERS Thiram detection

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Tau truncation in the pathogenesis of Alzheimer's disease:a narrative review

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Neural Regeneration Research 2024年第6期19卷 1221-1232页

作者： Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsCoinnovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina department of biochemistry and molecular biology School of MedicineNantong UniversityNantongJiangsu ProvinceChina department of Clinical Pharmacy Affiliated Maternity and Child Health Care Hospital of Nantong UniversityNantong UniversityNantongJiangsu ProvinceChina Laboratory of Animal center Nantong UniversityNantongJiangsu ProvinceChina department of Neurochemistry Inge Grundke-Iqbal Research FloorNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandNYUSA

Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau *** studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease *** physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like *** addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent *** review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.

关键词： Alzheimer's disease cleavage site diagnosis marker neurofibrillary tangles phosphorylation Tau Tau aggregation therapy truncation

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FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury

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Military Medical Research 2024年第4期11卷 521-542页

作者： Mi Zhou Yang-Wu-Yue Liu Yu-Hang He Jing-Yu Zhang Hao Guo Hao Wang Jia-Kui Ren Yi-Xun Su Teng Yang Jia-Bo Li Wen-Hui He Peng-Jiao Ma Man-Tian Mi Shuang-Shuang Dai department of biochemistry and molecular biology School of Basic MedicineArmy Medical UniversityChongqing 400038China Research center for Nutrition and Food Safety Chongqing Key Laboratory of Nutrition and HealthInstitute of Military Preventive MedicineArmy Medical UniversityChongqing 400038China department of Neurosurgery Daping HospitalArmy Medical UniversityChongqing 400042China department of Trauma and Emergency Southwest HospitalArmy Medical UniversityChongqing 400038China department of Histology and Embryology Chongqing Key Laboratory of NeurobiologyBrain and Intelligence Research Key Suyixun Laboratory of Chongqing Education CommissionArmy Medical UniversityChongqing 400038China Research center Seventh Affiliated Hospital of Sun Yat-Sen UniversityShenzhen 518107GuangdongChina

Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly ***:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral *** also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout ***:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse *** of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced *** the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high *** the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression afte

关键词： Traumatic brain injury(TBI) Neutrophil Forkhead box protein O1(FOXO1) Acute stage Chronic stage

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Manipulating guest-responsive spin transition to achieve switchable fluorescence in a Hofmann-type framework

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science China Chemistry 2024年第10期67卷 3339-3346页

作者： Xue-Ru Wu Shu-Qi Wu Zhi-Kun Liu Ming-Xing Chen Jun Tao Osamu Sato Hui-Zhong Kou Engineering Research center of Advanced Rare Earth Materials(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing 100084China Institute for Materials Chemistry and Engineering&IRCCS Kyushu University744 MotookaNishi-kuFukuoka 819-0395Japan Key Laboratory of Cluster science of Ministry of Education School of Chemistry and Chemical EngineeringLiangxiang CampusBeijing Institute of TechnologyBeijing 102488China Analytical Instrumentation center College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

The change of fluorescence emission manipulated by spin state transition attracts considerable attention owing to its potential applications in magneto-optical switching ***,we report two two-dimensional(2D)Hofmann-type spin crossover(SCO)metal-organic frameworks(MOFs)[Fe^(Ⅱ)(PNI)_(2){Ag^(Ⅰ)(CN)_(2)}_(2)]·CHCl_(3)(3Ag·CHCl_(3))and[FeⅡ(PNI)_(2){AuⅠ(CN)_(2)}_(2)]·CHCl_(3)(3Au·CHCl_(3))based on the fluorescent ligand N-(4-pyridylmethyl)-1,8-naphthalimide(PNI).Both complexes exhibit interesting SCO behaviors switched by guest solvent molecules,namely three-step transitions for the solvated complexes and complete onestep hysteretic SCO for the desolvated ones,verified by temperature-dependent magnetic susceptibility measurements,Mossbauer spectra,structural analyses,and differential scanning calorimetry ***,temperature-dependent fluorescence spectra exhibit double peaks(monomer and excimer emission)with both emission peaks change consistent with the change in SCO properties during the solvent molecule *** this study,we integrated guest-responsive SCO behavior into MOFs to manipulate the multistability of spin state and fluorescence switching,providing a rational strategy for the development of stimuli-responsive multifunctional materials.

关键词： spin crossover fluorescence multifunctional materials metal-organic frameworks Hofmann-type

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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DNA methylation drives a new path in gastric cancer early detection:Current impact and prospects

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Genes & Diseases 2024年第2期11卷 847-860页

作者： Xinhui Wang Yaqi Dong Hong Zhang Yinghui Zhao Tianshu Miao Ghazal Mohseni Lutao Du Chuanxin Wang department of Clinical Laboratory The Second Hospital of Shandong UniversityJinanShandong 250033China department of Clinical Laboratory Fuling HospitalChongqing UniversityChongqing 402774China Suzhou Research Institute of Shandong university SuzhouJiangsu 215123China department of biochemistry and molecular biology Shandong University School of Basic Medical SciencesJinanShandong 250012China Shandong Engineering & Technology Research center for Tumor Marker Detection JinanShandong 250033China Shandong Provincial Clinical Medicine Research center for Clinical Laboratory JinanShandong 250033China

Gastric cancer(GC)is one of the most common and deadly cancers *** detection offers the best chance for curative treatment and reducing its ***,the optimal population-based early screening for GC remains *** DNA methylation occurs in the early stage of GC,exhibiting cancer-specific genetic and epigenetic changes,and can be detected in the media such as blood,gastric juice,and feces,constituting a valuable biomarker for cancer early ***,DNA methylation is a stable epigenetic alteration,and many innovative methods have been developed to quantify it rapidly and ***,large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking,precluding their implementation in clinical *** conclusion,after a critical analysis of the recent existing literature,we summarized the evolving roles of DNA methylation during GC occurrence,expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC,and discussed its challenges and prospects in clinical applications.

关键词： Biomarkers DNA methylation Early detection Gastric cancer Translation

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BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/ Stat3 pathway in mesenchymal stem cells

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Genes & Diseases 2024年第3期11卷 468-483页

作者： Jie Zhang Jinhai Jiang Hang Liu Shiyu Wang Kaixin Ke Siyuan Liu Yue Jiang Lu Liu Xiang Gao Baicheng He Yuxi Su department of Pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Key Laboratory of biochemistry and molecular Pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China department of Orthopedics Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China orthopedics department Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International science and Technology Cooperation Base of Child Development and Critical Disorders Jiangxi Hospital Affiliated Children's Hospital of Chongqing Medical UniversityJiangxi 330000China National Clinical Research center for Child health and Disorders China

Bone defects and non-union are prevalent in clinical orthopedy,and the outcomes of current treatments are often *** tissue engineering offers a promising approach to treating these conditions *** morphogenetic protein 9(BMP9)can commit mesenchymal stem cells to osteogenic lineage,and a knowledge of the underlying mechanisms may help advance the field of bone tissue ***-rich repeats con-taining G protein-coupled receptor 4(LGR4),a member of G protein-coupled receptors,is essential for modulating bone *** study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying *** marrow stromal cells from BMp9-knockout mice exhibited diminished LGR4 expression,and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal ***,LGR4 expression was increased by BMP9 in C3H10T1/2 ***4 augmented the benefits of BMP9-induced osteogenic markers and bone formation,whereas LGR4 inhibition restricted these ***,the BMP9-induced li-pogenic markers were increased by LGR4 *** protein levels of Raptor and p-Stat3 were elevated by *** knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by ***4 significantly reversed the blocking ef-fect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic *** interacts with p-Stat3,and p-Stat3 activates the LGR4 promoter *** conclusion,LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells,and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词： BMP9 LGR4 mTORC1 Osteogenic differentiation Stat3

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