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A systematic review of salivary biomarkers in Parkinson's disease

Neural Regeneration research 2024年第12期19卷 2613-2625页

作者： Maria Ilenia De Bartolo Daniele Belvisi Romina Mancinelli Matteo Costanzo Claudia Caturano Giorgio Leodori Alfredo Berardelli Giovanni Fabbrini Giorgio Vivacqua IRCCS Neuromed PozzilliItaly Department of Human Neurosciences Sapienza University of RomeRomeItaly Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly Department of experimental Morphology and Microscopy-Integrated research Center(PRAAB)-Campus Biomedico University of Rome RomeItaly

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying *** the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection *** represents an easily accessible biofluid and an incredibly wide source of molecular *** the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of *** screening and exclusion,34 relevant articles were derived fo r systematic ***-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's *** alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network

关键词： alpha-synuclein amyloid-beta autophagy DJ-1 neurodegeneration neuroinflammation Parkinson's disease salivary biomarkers tau

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Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of Biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for experimental Therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial Biotechnology research Group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and Therapeutics research Group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem Cell and Regenerative Medicine research Group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma Cell cycle heterogeneity Quiescence Therapy resistance Therapy tolerance Tumor dormancy

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Elucidating and manipulating pressure-induced water intrusion–extrusion in tunable hydrophobic Co/Zn bimetallic ZIFs:Roles of pore size and hydrogen bond

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Nano research 2024年第1期17卷 344-353页

作者： Diyi Fang Chuanlei Liu Yu Chen Qilong Peng Kongguo Wu Yuxiang Chen Hao Jiang Yuan Wu Benxian Shen Qiumin Wu Di Wu Hui Sun International Joint research Center of Green Energy Chemical Engineering School of Chemical EngineeringEast China University of Science and TechnologyShanghai 200237China Alexandra Navrotsky Institute for experimental Thermodynamics The Gene and Linda Voiland School of Chemical Engineering and BioengineeringMaterials Science and Engineeringand Department of ChemistryWashington State UniversityWashington 99163USA

Porous heterogeneous lyophobic systems(HLSs)find potential applications in energy restoring,dissipating,and ***,the development of controllable HLSs still lacks rational structure design of nanoporous materials matching the molecular sizes of adopted *** that,thoroughly understanding the underlying transportation mechanism in the confined nano channels is greatly *** this work,a series of Co/Zn bimetallic zeolitic imidazolate frameworks(ZIFs)with tunable structures were synthesized via regulating the Co to Zn ratios and employed to investigate the intrusion–extrusion of liquid water in confined *** characterizations confirm the heterometallic coordination in the Co/Zn-doped *** intrusion–extrusion experiments unlock the relationship between the intrusion pressure and the nanopore size and realize the evolution of the HLSs between molecular spring and *** addition,cycling tests indicate the reversible structure change of Co/Zn ZIFs encountering pressure-induced water *** combination with molecular dynamics simulations,we present that the water multimers intrude into nanopores of ZIFs in chain-like forms along with dissociation of hydrogen bonds(HBs).Water molecules in the pre-intrusion state exhibit reduced HBs in response to the increase of pressure and linear structure with 1.6–3.0 HBs on *** transition to the post-intrusion situation,the associative configuration of water tends to exhibit the tetrahedral ***,we highlight the roles of pore size and HB in synergically dominating the pressure-induced intrusion–extrusion of liquid water in hydrophobic ***,the present work can also guide the development of functional guest–host systems based on porous architectures.

关键词： heterometallic zeolitic imidazolate frameworks nanopore intrusion hydrogen bonds

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Systemic analysis of metabolome reconfiguration in Arabidopsis after abiotic stressors uncovers metabolites that modulate defense against pathogens

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Plant Communications 2024年第1期5卷 55-68页

作者： Antoni Garcia-Molina Victoria Pastor Centre for research in Agricultural Genomics(CRAG)CSIC-IRTA-UAB-UB C/Vall MorontaEdifici CRAG08193 Bellaterra(Cerdanyola del Valles)BarcelonaSpain Department of Biology Biochemistryand Natural SciencesSchool of Technology and Experimental SciencesUniversitat Jaume I12006 Castellode la PlanaSpain

Understanding plant immune responses is complex because of the high interdependence among biological processes in homeostatic ***,the integration of environmental cues causes network rewiring that interferes with defense ***,plants retain molecular signatures configured under abiotic stress periods to rapidly respond to recurrent stress,and these can alter *** changes imposed by abiotic stressors are persistent,although their impact on defense remains to be *** this study,we profiled metabolomes of Arabidopsis plants under several abiotic stress treatments applied individually or simultaneously to capture temporal trajectories in metabolite composition during adverse conditions and *** systemic analysis was performed to address the relevance of me-tabolome changes and extract central features to be tested in *** results demonstrate irreversibility in major fractions of metabolome changes as a general pattern in response to abiotic stress ***-tionalanalysisofmetabolomesandco-abundancenetworkspoints toconvergence inthereconfigurationof organic acid and secondary metabolite *** mutant lines for components related to these metabolic pathways showed altered defense capacities against different ***,our data suggest that sustained metabolome changes configured in adverse environments can act as mod-ulators of immune responses and provide evidence for a new layer of regulation in plant defense.

关键词： abiotic stress Arabidopsis biotic stress combinatorial stress metabolomics systems biology

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Hole-Doped Nonvolatile and Electrically Controllable Magnetism in van der Waals Ferroelectric Heterostructures

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Chinese Physics Letters 2024年第5期41卷 107-119页

作者：姜新新王智宽李冲孙雪莲杨磊李冬梅崔彬刘德胜 School of Physics National Demonstration Center for Experimental Physics EducationShandong UniversityJinan 250100China School of Physics and Microelectronics Zhengzhou UniversityZhengzhou 450001China

Electrical control of magnetism in van der Waals semiconductors is a promising step towards development of two-dimensional spintronic devices with ultralow power consumption for processing and storing ***, we propose a design for two-dimensional van der Waals heterostructures(vdWHs) that can host ferroelectricity and ferromagnetism simultaneously under hole doping. By contacting an In Se monolayer and forming an InSe/In_(2)Se_(3) vd WH, the switchable built-in electric field from the reversible out-of-plane polarization enables robust control of the band alignment. Furthermore, switching between the two ferroelectric states(P_↑ and P_↓)of hole-doped In_(2)Se_(3) with an external electric field can interchange the ON and OFF states of the nonvolatile magnetism. More interestingly, doping concentration and strain can effectively tune the magnetic moment and polarization energy. Therefore, this provides a platform for realizing multiferroics in ferroelectric heterostructures,showing great potential for use in nonvolatile memories and ferroelectric field-effect transistors.

关键词： polarization ferroelectric doping

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

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Animal Models and experimental Medicine 2024年第1期7卷 77-81页

作者： Tatsushi Mutoh Ryota Tochinai Hiroaki Aono Masayoshi Kuwahara Yasuyuki Taki Tatsuya Ishikawa Department of Surgical Neurology Research Institute for Brain and Blood VesselsAkita Cerebrospinal and Cardiovascular CenterAkitaJapan Department of Aging research and Geriatric Medicine Institute of DevelopmentAging and CancerTohoku UniversitySendaiJapan Department of Veterinary Pathophysiology and Animal Health Graduate School of Agriculture and Life SciencesThe University of TokyoTokyoJapan

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are ***,we introduce a simple procedure for se-lecting a mouse model of diffuse *** was induced in 24 mice using a standard filament perforation *** confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura *** CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,pexperimental studies.

关键词： cisterna magna clot distribution filament perforation mouse model subarachnoid hemorrhage

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AP4 induces JNK1 and a miR-22-3p/FOSL1 feed-forward loop to activate AP-1 and promote colorectal cancer metastasis

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Cancer Communications 2024年第3期44卷 433-437页

作者： Jinjiang Chou Markus Kaller Matjaz Rokavec Fangteng Liu Heiko Hermeking experimental and Molecular Pathology Institute of PathologyMedical FacultyLudwig-Maximilians-Universität MünchenMunichGermany German Cancer Consortium(DKTK) Partner siteMunichGermany German Cancer research Center(DKFZ) HeidelbergGermany

Dear Editor,Colorectal cancer(CRC)is the third most deadly can-cer worldwide[1].The mortality of CRC has remained high due to limited treatment options for metastatic CRC(mCRC)[2].Epithelial-mesenchymal transition(EMT)is an important contributor to mCRC[2].The c-MYC proto-oncogene(MYC)-induced transcription factor AP4(TFAP4/AP4)isadriverofEMT,therebypresumablyfacil-itates mCRC[3,4].The mitogen-activated protein kinase(MAPK)/c-JunN-terminalkinase(JNK)/activatorprotein-1(AP-1)pathway has been implicated in the regulation of EMT and mCRC[5].

关键词： JNK1 metastasis EMT

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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A new monitoring index for ecological vulnerability and its application in the Yellow River Basin,China from 2000 to 2022

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Journal of Arid Land 2024年第9期16卷 1163-1182页

作者： GUO Bing XU Mei ZHANG Rui LUO Wei School of Civil Engineering and Geomatics Shandong University of TechnologyZibo 255000China Key Laboratory of Remote Sensing of Gansu Province Heihe Remote Sensing Experimental Research StationNorthwest Institute of Eco-Environment and ResourcesChinese Academy of SciencesLanzhou 730000China North China Institute of Aerospace Engineering Langfang 065000China

The ecological environment of the Yellow River Basin has become more fragile under the combined action of natural and manmade ***,the change mechanisms of ecological vulnerability in different sub-regions and periods vary,and the reasons for this variability are yet to be ***,in this study,we proposed a new remote sensing ecological vulnerability index by considering moisture,heat,greenness,dryness,land degradation,and social economy indicators and then analyzed and disclosed the spatial and temporal change patterns of ecological vulnerability of the Yellow River Basin,China from 2000 to 2022 and its driving *** results showed that the newly proposed remote sensing ecological vulnerability index had a high accuracy,at 86.36%,which indicated a higher applicability in the Yellow River *** 2000 to 2022,the average remote sensing ecological vulnerability index of the Yellow River Basin was 1.03,denoting moderate vulnerability *** intensive vulnerability area was the most widely distributed,which was mostly located in the northern part of Shaanxi Province and the eastern part of Shanxi *** 2000 to 2022,the ecological vulnerability in the Yellow showed an overall stable trend,while that of the central and eastern regions showed an obvious trend of *** gravity center of ecological vulnerability migrated southwest,indicating that the aggravation of ecological vulnerability in the southwestern regions was more severe than in the northeastern regions of the *** dominant single factor of changes in ecological vulnerability shifted from normalized difference vegetation index(NDVI)to temperature from 2000 to 2022,and the interaction factors shifted from temperature∩NDVI to temperature∩precipitation,which indicated that the global climate change exerted a more significant impact on regional *** above results could provide decision support for the ecological protection and restoration of the Y

关键词： ecological vulnerability spatio-temporal pattern gravity center migration trajectory interaction factors geodetector green index q-value

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