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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt Hans Zempel Institute of human genetics University Hospital CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

Surfing the nano-wave:Emerging trends in cancer diagnostics and therapy

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Nano Research 2025年第1期18卷 520-544页

作者： Genping Fu Yuting Weng Yunfan Li Carl Ho Yiyu Fu Wenxuan Wang Songbin Fu Wenjing Sun Jie Lin Xiaoyu Fan Binbin Jia Mengdi Cai Linlin Li laboratory of Medical genetics Harbin Medical UniversityHarbin 150081China Key laboratory of Preservation of human genetics Resources and Disease Control in China(Harbin Medical University) Ministry of EducationHarbin 150081China Beijing Key laboratory for Optical Materials and Photonic Devices Department of ChemistryCapital Normal UniversityBeijing 100048China College of Materials and Chemical Engineering Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion MaterialsChina Three Gorges UniversityYichang 443002China Washington University School of Medicine in St.Louis St.LouisMO 63110USA Ningbo Institute of Materials Technology and Engineering Chinese Academy of SciencesNingbo 315201China Aix-Marseille College Wuhan University of TechnologyWuhan 430070China

Facing the growing global challenge posed by cancer,the quest for more accurate and potent cancer diagnostic and therapeutic strategies continues to require a multidisciplinary integration *** review firstly summarizes various types of nanoparticles in cancer ***,it offers a comprehensive overview of signalenhancing techniques for visualizing in situ tumors,along with multimodal diagnostic methods for detecting *** for tumor therapy,cutting-edge drug delivery methods that can cross biological barriers and the pinpoint targeting of tumor lesions for precise medical intervention are *** the domain of therapeutic diagnostics,we elucidate the theoretical underpinnings and structural paradigms that underlie a spectrum of advanced diagnostic and therapeutic ***,we present a compendium of publications delineating the clinical applications of each nano-based theragnostic integration ***,this comprehensive review discusses the safety concerns pertaining to the clinical application of nanoparticles and proposes some strategic recommendations to enhance the precision and safety of theragnostic-guided,nanotechnology-based clinical practices.A deeper understanding of nanomaterials,together with intimate interdisciplinary collaborations,nano-wave will most probably guide human beings to win the battle against cancers.

关键词： nanoparticles drug delivery gastric cancer glioma glioblastoma

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International human Phenome Institutes(Shanghai) ShanghaiChina human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of human genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

sFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma

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Hepatobiliary & Pancreatic diseases International 2015年第2期14卷 164-170页

作者： Cheng Xu Xiang-Hua Zeng Li Wang Shi-Qi Tao Quan-Xin Wu Peng Zhu Guo-Hong Deng Yu-Ming Wang Institute of infectious diseases Southwest HospitalThird Military Medical University Chongqing Key laboratory for Research of infectious diseases

BACKGROUND：The current methods used for diagnosing hepatocellular carcinoma（HCC）are ***,we assessed the serum levels of secreted frizzled related protein 4（s FRP-4）for diagnosing HCC in patients infected with chronic hepatitis B（CHB）.METHODS：In 272 patients with CHB enrolled,142 were pa tients with ***-three healthy subjects were recruited as healthy *** CHB patients were assigned to a test group or a validation group based on the time of enrollment. human antibody arrays were used to screen 15 patients （8 CHB-related HCC patients, 7 CHB patients） for serum mark- ers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. RESULTS： human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients （P〈0,05）. Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group （79.7 vs 41.3 ng/mL; P〈0.001） and validation group （89.0 vs 39.0 ng/mL; P〈0.001）. Areas under the Receiver Operating Charac- teristic curves （AUCs） for alpha-fetoprotein （AFP） and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 （a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL） and AFP （a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL） showed better performance for diagnosing HCC （a sensitivity of 79.2% and a specificity of 95.3%）. The AUC for combined sFRP-4 and AFP increased to 0.941 （95% CI： 0.908-0.975）, and similar results were seen in the validation group. CONCLUSION： sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.

关键词： chronic hepatitis B hepatocellular carcinoma s FRP-4 serum marker

Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

Kaposi’s sarcoma manifested as lower gastrointestinal bleeding in a HIV/HBV-co-infected liver cirrhosis patient: A case report

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World Journal of Clinical Cases 2019年第19期7卷 3090-3097页

作者： Qi-Hui Zhou Yong-Zheng Guo Xia-Hong Dai Biao Zhu The Department of infectious diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital College of Medicine Zhejiang University

BACKGROUND Kaposi’s sarcoma(KS)is one of the most common cancers in human immunodeficiency virus(HIV)-positive patients and leads to a high prevalence of morbidity and *** usually appears as cutaneous or mucous *** with visceral KS are asymptomatic and clinically *** the disease advances,patients may progress from a normal condition to exhibiting severe *** SUMMARY A 27-year-old man presented with a 2-mo history of fever,bearing-down pain,and rectal *** hepatitis B virus DNA level was 2.7×107 IU/*** computed tomography(CT)indicated liver *** he was admitted to our hospital,he was diagnosed with HIV *** CD4 count was 24 cells/μ*** cavity CT suggested a thickened rectum wall accompanied by multiple enlarged lymph *** patient was initially treated as having haemorrhoidal varices with bleeding,telbivudine for anti-hepatitis B virus treatment,and antibiotics for *** half a month of treatment,the patient felt that his lower lumbus ache and bearing-down pain had not improved,and a colonoscopy was *** result revealed a rectal mass that was histologically confirmed as KS with rectal spindle cells that were positive for cluster of differentiation 117(CD117),CD34,human herpes virus 8,and *** was administered systemic chemotherapy with 36 mg/d liposomal doxorubicin six *** patient experienced no sign of lower gastrointestinal bleeding *** This case highlights the diagnosis of primary KS with lower gastrointestinal bleeding in HIV-positive patients,which means visceral KS could not be *** gold standard relies on colonoscopy and biopsy findings.

关键词： human immunodeficiency virus/hepatitis B virus co-infection Kaposi’s Sarcoma Lower gastrointestinal bleeding Colonoscopy Immunohistochemistry Case report

Refrigeration temperature enhanced synergistic interaction of curcumin and 460 nm light-emitting diode against Staphylococcus saprophyticus at neutral pH

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Food Quality and Safety 2021年第1期5卷 15-21页

作者： Ziyuan Wang Lin Han Jie Liu Mingfei Yao Beijing Advanced Innovation Center for Food Nutrition and human Health Beijing Technology and Business UniversityBeijingChina State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina

Objectives:As considered highly resistant to antibiotics like mecillinam,the rise of Staphylococcus saprophyticus(***)contamination of fresh foods and food processing environments necessitates the development of a new antimicrobial approach for food safety *** study aimed to investigate the synergistic effect of food-grade curcumin(CUR)and blue light-emitting diode(LED)on *** and Methods:***/ciys was subjected to the synergistic treatment at 4℃ and 25℃.The influence of parameters,including CUR concentration,light dose,and pH incubation time on the inactivation of *** vjqs characterized through plate counting ***:The combined treatment of CUR and blue light irradiation significantly(P<0.05)reduced bacterial counts and the antimicrobial effect was in a CUR concentration and light dose-dependent ***,refrigeration temperature(4℃)significantly(P<0.05)enhanced the antibacterial effect at neutral pH condition(6.2-72),resulting in approximately 6.0 log *** acidic condition(pH 2.2-5.2),there was no significant difference in bacterial population reduction between treatments at both ***:These findings proposed that synergistic interaction of CUR and 460 nm LED under refrigerated temperature could enhance the inactivation of *** at neutral pH condition.

关键词： curcumin light-emitting diode pH refrigeration temperature Staphylococcus saprophyticus

Role of main RNA modifications in cancer:N^(6)-methyladenosine,5-methylcytosine,and pseudouridine

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1555-1585页

作者： Chen Xue Qingfei Chu Qiuxian Zheng Shiman Jiang Zhengyi Bao Yuanshuai Su Juan Lu Lanjuan Li State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China

Cancer is one of the major diseases threatening human life and health *** modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic *** modifications regulate many biological processes,such as growth,aging,and various diseases,including *** the advancement of next-generation sequencing technology,the role of RNA modifications in cancer progression has become increasingly prominent and is a hot spot in scientific *** review studied several common RNA modifications.

关键词： diseases cancer Cancer