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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Neural Regeneration Research 2025年第1期20卷 41-53页

作者： alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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免疫疗法联合立体定向放疗治疗非小细胞肺癌脑转移:一项AIRO多中心回顾性研究

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中国肺癌杂志 2022年第4期25卷 I0007-I0022页

作者： Silvia SCOCCIANTI Emanuela OLMETTO Valentina PINZI Mattia Falchetto OSTI Rossella Di FRANCO Saverio CAINI Paola ANSELMO Paolo MATTEUCCI Davide FRANCESCHINI Cristina MANTOVANI Giancarlo BELTRAMO Francesco PASQUALETTI alessio bruni Paolo TINI Emilia GIUDICE Patrizia CIAMMELLA Anna MERLOTTI Sara PEDRETTI Marianna TRIGNANI Marco KRENGLI NiccolòGIAJ-LEVRA Isacco DESIDERI Guido PECCHIOLI Paolo MUTO Ernesto MARANZANO Laura FARISELLI Pierina NAVARRIA Umberto RICARDI Vieri SCOTTI Lorenzo LIVI 王绿化(翻译/校对) Radiation Oncology Unit Ospedale Santa Maria AnnunziataDepartment of OncologyBagno a RipoliFlorenceItaly Radiation Oncology Unit Azienda Ospedaliero Universitaria CareggiDepartment of Experimental and Clinical Biomedical Sciences"Mario Serio"FlorenceItaly U.O Radioterapia Fondazione IRCCS Istituto Neurologico Carlo BestaDepartment of NeurosurgeryMilanItaly U.O.C Radioterapia A.O.U Sant'Andrea Facolta Medicina e Psicologia Universita SapienzaDepartment of MedicineSurgery and Translational MedicineRomeItaly Istituto Nazionale Tumori IRCCS Fondazione G.PascaleDepartment of RadiotherapyNaplesItaly Institute for Cancer Research Prevention and Clinical Network(ISPRO)Cancer Risk Factors and Life-Style Epidemiology UnitFlorenceItaly Radiotherapy Oncology Center S.Maria HospitalDepartment of OncologyTerniItaly Humanitas Research Hospital Radiotherapy and Radiosurgery DepartmentRozzanoItaly Radiotherapy Unit Department of OncologyTurinItaly Cyberknife Centro Diagnostico Italiano Department of RadiologyMilanItaly Radiation Oncology Azienda Ospedaliero Universitaria PisanaDepartment of Translational MedicinePisaItaly Radiotherapy Unit University Hospital of ModenaDepartment of Oncology and HematologyModenaItaly Radiotherapy Unit University of SienaDepartment of Radiotherapy and OncologySienaItaly UOC di Radioterapia Policlinico Universitario Tor VergataDepartment of Onco-HaematologyRomeItaly Radioterapia Oncologica"G.Prodi "AO-IRCCS Arcispedale S.Maria NuovaDepartment of Oncology and Advanced TechnologyReggio EmiliaItaly Radiation Oncology A.S.O.S.Croce e Carle Department of Radiation OncologyCuneoItaly U.O.Radioterapia Oncologica Department of Radiation OncologyASST Spedali Civili di Brescia e Universita degli studi di BresciaBresciaItaly U.O.C.Radioterapia Oncologica Ospedale Clinicizzato SS Annunziata-Universita Chieti G.D'AnnunzioDepartment of Radiation OncologyChietiItaly Radiation Oncology University Hospital Maggiore della CaritdDepartment of Translational Medicine

背景与目的通过意大利放射治疗和临床肿瘤学学会(Italian Association of Radiotherapy and Clinical Oncology, AIRO)的一项多中心回顾性研究,明确免疫疗法(immunotherapy, IT)和立体定向放疗(stereotactic radiotherapy,SRT)包括放射外科治疗(radiosurgery, RS)或大分割立体定向放疗(hypofractionated stereotactic radiotherapy, HFSRT)治疗非小细胞肺癌(non-small cell lung cancer, NSCLC)脑转移的疗效和毒性。方法对来自19个意大利中心接受SRT+IT的NSCLC伴脑转移患者进行分析,并与单独接受SRT的对照组患者进行比较。结果共纳入SRT+IT组100例和单独SRT组50例。接受SRT+IT的患者有更长的颅内局部无进展生存期(intracranial local progression-free survival, i LPFS)(经倾向性评分调整后,P=0.007)。在诊断为脑转移时接受IT合并有颅外进展的患者中(n=24),接受SRT后再进行IT与较好的总生存期(overall survival, OS)相关(P=0.037)。多因素分析显示组织学类型为非腺癌、卡氏体能状态(Karnofsky performance status,KPS)评分=70分以及接受HFSRT与显著减少的生存期相关(P值分别为0.019、0.017和0.007)。与SRT和IT治疗间隔>7天(n=10)相比,治疗间隔≤7天(n=90)与更长的OS相关(经倾向性评分调整后,P=0.008)。联合治疗耐受性良好。在放射性坏死方面,接受SRT+IT的患者与单独SRT的患者无显著差异。SRT和IT的治疗间隔对毒性发生率无影响。结论 SRT+IT是一种安全的联合治疗方法,与单独SRT相比,具有更长的i LPFS。

关键词：立体定向放疗回顾性研究脑转移倾向性评分临床肿瘤学免疫疗法放射治疗

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Is dual therapy the correct strategy in frail elderly patients with atrial fibrillation and acute coronary syndrome?

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Journal of Geriatric Cardiology 2020年第1期17卷 51-57页

作者： alessio Menditto Roberto Antonicelli Cardiology Unit Italian National Research Centre on Aging

Atrial fibrillation(AF)is a very common arrhythmia in clinical *** incidence and prevalence are age-related and are growing in the last *** is a risk factor also for coronary artery disease(CAD),and with the evolution of preventive care,the first event(acute coronary syndrome(ACS)or percutaneous coronary intervention(PCI))takes place at a later *** elderly patients with AF and CAD undergo ACS or PCI,they have indication to assume triple *** therapy(oral anticoagulation(OAC)plus dual antiplatelet therapy(DAPT))exposes patients to high bleeding *** the last 10 years,several clinical trials have tested dual therapy(OAC plus single antiplatelet therapy)in AF patients who undergo ACS or elective *** trial has tested warfarin+clopidogrel against triple *** AF-PCI trial has tested low-dose rivaroxaban+P2Y12 inhibitor or very low-dose rivaroxaban+DAPT against standard triple therapy with ***-DUAL PCI trial has tested two doses of dabigatran+P2Y12 inhibitor against standard triple therapy with *** trial has tested apixaban against warfarin both in dual therapy with P2Y12 inhibitor and in triple therapy with a P2Y12 inhibitor and ***-AF PCI,last published study,has tested edoxaban+P2Y12 inhibitor against triple *** these trials show dual therapy reduces significantly bleeding risk than triple *** this paper,we analyze these clinical trials to understand if dual therapy results can be applied to elderly patients and what is probably the better approach in elderly AF patients undergo to ACS or PCI.

关键词： Acute coronary syndrome Atrial fibrillation Dual therapy Oral anticoagulation The elderly

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Quantitative Stability of the Brunn-Minkowski Inequality for Sets of Equal Volume(Dedicated to Professor Haim Brezis on the occasion of his 70th birthday)

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Chinese Annals of Mathematics,Series B 2017年第2期38卷 393-412页

作者： alessio FIGALLI David JERISON The University of Texas at Austin Mathematics Dept.RLM 8.1002515 Speedway Stop C1200AustinTX 78712-1202USA. Department of Mathematics Massachusetts Institute of Technology77 Massachusetts AveCambridgeMA 02139-4307 USA.

The authors prove a quantitative stability result for the Brunn-Minkowski inequality on sets of equal volume: If |A| = |B| > 0 and |A + B|^(1/n) =(2 + δ)|A|^(1/n) for some small δ, then, up to a translation, both A and B are close(in terms of δ) to a convex set *** this result was already proved by the authors in a previous paper, the present paper provides a more elementary proof that the authors believe has its own interest. Also,the result here provides a stronger estimate for the stability exponent than the previous result of the authors.

关键词： Quantitative stability, Brunn-Minkowski, Affine geometry, Convexgeometry, Additive combinatorics

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Zonula occludin toxin,a microtubule binding protein

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World Journal of Gastroenterology 2000年第3期6卷 330-334页

作者： MariaRosaria DiPierro alessio Fasano Center for Vaccine Development Division of Gastroenterology University of Baltimore at MarylandBaltimoreMD 21201USA

AIM To investigate the interaction of Zot *** Zot affinity column was applied topurify Zot-binding protein（s）from crudeintestinal cell *** incubation at roomtemperature,the column was washed and theproteins bound to the Zot affinity column wereeluted by step gradient with NaCl(0.3 mol·L-1-0.5mol·L-1).The fractions were subjected to6.0%-15.0%（w/v）gradient SDS-PAGE andthen transferred to PVDF membrane for N-terminal *** Zot and tauprotein were blotted by using anti-Zot or ***,purified Zot was tested in anin vitro tubulin binding *** Fractions from Zot affinity columnyielded two protein bands with a Mr of 60 kU and45kU *** N-terminal sequence ofthe 60 kU band resulted identical to β-*** also cross-reacts with anti-tau *** in vitro tubulin binding assay,Zot co-precipitate with Mt,further suggesting that Zotpossesses tubulin-binding *** Taken together,these resultssuggest that Zot regulates the permeability ofintestinal tight junctions by binding tointracellular Mt,with the subsequent activationof the intracellular signaling leading to thepermeabilization of intercellular tight junctions.

关键词： microtubules microtubule proteins microtubule-associated proteins intercellular junctions vibrio cholerae cholera toxin zonula occluding toxin

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Evidence on neuroprotective properties of coenzyme Q10 in the treatment of glaucoma

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Neural Regeneration Research 2019年第2期14卷 197-200页

作者： alessio Martucci Carlo Nucci Ophthalmology Unit Department of Experimental Medicine University of Rome Tor Vergata

Glaucoma, the leading cause of visual impairment and irreversible blindness worldwide, is a multifactorial, progressive optic neuropathy characterized by loss of retinal ganglion cells, alterations of the optic nerve head, and specific visual field defects. Clinical evidence shows that intraocular pressure is the major risk factor of the treatable disease. However, in some patients, glaucoma develops and continues to progress despite normal intraocular pressure values, suggesting that other risk factors are involved in the disease. Consequently, neuroprotective treatments, focused on preventing retinal ganglion cells death by acting on different therapeutic strategies but not focused on intraocular pressure reduction, has therefore become of great interest. In this contest, coenzyme Q10, showing evidence in slowing or reversing pathological changes typical of the disease, has been proposed as a potential neuroprotective agent in glaucoma. In this review, we describe the possible mechanisms of action of coenzyme Q10 and the recent evidence in literature regarding the neuroprotective activity of the molecule.

关键词： glaucoma neuroprotection retinal ganglion cells coenzyme Q10 intraocular pressure mitochondrion oral administration neurodegenerative diseases

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Groups with Finitely Many Homomorphic Images of Finite Rank

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Algebra Colloquium 2016年第2期23卷 181-187页

作者： Francesco de Giovanni alessio Russo Dipartimento di Matematica e Applicazioni Universitg di Napoli Federico II Complesso Universitario Monte S. Angelo Via Cintia 1-80126 Napoli Italy Dipartimento di Matematica e Fisica Seconda Universitg di Napoli Via Lincoln 5 1-81100 Caserta Italy

A group is called a Cernikov group if it is abelian-by-finite and satisfies the minimal condition on subgroups. A new characterization of Cernikov groups is given here, by proving that in a suitable large class of generalised soluble groups they coincide with the groups having only finitely many homomorphic images of finite rank （up to isomorphisms） and admitting an ascending normal series whose factors have finite rank.

关键词： Prufer rank Cernikov group homomorphic image

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Hypergeometric equations and weighted projective spaces

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Science China Mathematics 2011年第8期54卷 1577-1590页

作者： CORTI alessio GOLYSHEV Vasily Department of Mathematics Imperial College London Algebra and Number Theory Sector Institute for Information Transmission Problems

We compute the Hodge numbers of the polarised(pure) variation of Hodge structure V = grn-1WRn-1f!Z of the Landau-Ginzburg model f:Y → C mirror-dual to a weighted projective space wPn in terms of a variant of Reid's age function of the anticanonical cone over *** implies,for instance,that wPn has canonical singularities if and only if hn-1,0V = *** state a conjectural formula for the Hodge numbers of general hypergeometric *** show that a general fibre of the Landau-Ginzburg model is birational to a Calabi-Yau variety if and only if a general anticanonical section of wP is *** analyse the 104 weighted 3-spaces with canonical singularities,and show that a general anticanonical section is not a K3 surface exactly in those 9 cases where a generic fibre of the Landau-Ginzburg model is an elliptic surface of Kodaira dimension 1.

关键词： mirror symmetry variations of Hodge structures hypergeometric functions weighted projective spaces Landau-Ginzburg models

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Role of nuclear receptors in breast cancer stem cells

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World Journal of Stem Cells 2016年第3期8卷 62-72页

作者： alessio Papi Marina Orlandi Department of Biological Geological and Environmental Science (BiGea) University of Bologna

The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells,capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells(CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs(BCSCs) are likely to sustain the growth of the primary tumour mass, as wellas to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

关键词： Cancer stem cells Hypoxia Inflammation Nuclear receptors Retinoids Peroxisome proliferator-activator receptors

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Fluctuations and time scales for bed-load sediment motion over a smooth bed

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International Journal of Sediment Research 2015年第4期30卷 321-327页

作者： Francesco Ballio alessio Radice Politecnico di Milano Dept.of Civil and Environmental Engineering

Results are presented for experiments of bed-load sediment transport over a plane,smooth *** smooth-bed configuration,though not adequate for mimicking natural streams,enables the effects of bed roughness to be filtered out,thus,highlighting the role of flow turbulence for particle *** were individually tracked along their paths,measuring position and velocity of the individual grains.A number of analyses were then applied to the data:probability density function,auto-correlation,and spectra of the grain *** Lagrangian time scales of particle motion were obtained and compared to available data for the turbulent flow field to determine a phenomenological interpretation of the process.

关键词： Bed load Smooth bed Sediment motion Particle velocity Fluctuations

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