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SERIneALanine Killer:SPT promiscuity inhibits tumour growth via intra-tumoral deoxysphingolipid production

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Signal Transduction and Targeted Therapy 2020年第1期5卷 219-220页

作者： Mattia falcone Oliver D.K.Maddocks University of Glasgow Institute of Cancer Sciences Wolfson Wohl Cancer Research CentreGarscube EstateGlasgow G611QHUK

In a recent article in Nature,Muthusami et al.1 highlight the promiscuity of serine palmitoyltransferase(SPT)for non-essential amino acids under low serine conditions,illustrating a previously unappreciated mechanism ... 详细信息

关键词： Killer SPT tumour

Review of primary sclerosing cholangitis with increased IgG4 levels

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world Journal of Gastroenterology 2020年第23期26卷 3126-3144页

作者： Charis D Manganis roger w Chapman Emma L Culver Translational Gastroenterology Unit and Oxford NIHR Biomedical Research Centre John Radcliffe HospitalOxford OX39DUUnited Kingdom

Primary sclerosing cholangitis(PSC) is a chronic progressive liver disease. Subtypes of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. we aim to summarise the clinical phenotype,disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. we reviewed Pub Med,MEDLINE and Embase with the search terms "primary sclerosing cholangitis","IgG4", and "IgG4-related sclerosing cholangitis(IgG4-SC)". Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSCnormal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features,organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes(B*07, DRB1*15), T-helper2 and T-regulatory cytokines(IL4, IL10,IL13) and chemokines(CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC,although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.

关键词： Primary sclerosing cholangitis IgG4 IgG4-related disease IgG4-related sclerosing cholangitis

A machine learning approach to predict response to immunotherapy in type 1 diabetes

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Cellular & Molecular Immunology 2021年第3期18卷 515-517页

作者： Georgia Fousteri Ely Montee Rodrigues Gian Maria Giamporcaro Marika falcone Regulation of Adaptive immunity Unit Transplantation and Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Experimental Diabetes Unit Division of ImmunologyTransplantation and Infectious DiseasesDiabetes Research Institute(DRI)IRCCS San Raffaele Scientific InstituteMilanItaly

Type 1 diabetes(T1D)is an autoimmune disease mediated by selfreactive T cells that destroy insulin-producing β cells of the pancreatic islets.1 The disease is a complex multifactorial disorder resulting from a poorly defined interaction between genetic and environmental *** 40-50% of the disease risk is linked to genes,with the remaining risk arising from environmental factors.

关键词： diabetes immunotherapy autoimmune

Analysis of spontaneous adverse drug reactions to echinacea, valerian,black cohosh and ginkgo in Australia from 2000 to 2015

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Journal of Integrative Medicine 2019年第5期17卷 338-343页

作者： Claire L.Hoban roger w.Byard Ian F.Musgrave Discipline of Pharmacology The University of AdelaideAdelaideSA 5005Australia Discipline of Anatomy and Pathology The University of AdelaideAdelaideSA 5005Australia

Objective: Assessing adverse drug reactions(ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia(and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea(Echinacea purpurea), valerian(Valeriana officinalis), black cohosh(Actaea racemosa) and ginkgo(Ginkgo biloba).Methods: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration(TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using Graph Pad Prism ***: Most ADRs were mild or moderate. However, every herbal medicine was associated with lifethreatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs(30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or ***: This study highlights the lack of public awareness with regard to herb–drug interactions,since most of the severe ADRs involved a herb–drug interaction.

关键词： Herbal medicine Adverse drug reaction Actaea racemosa Echinacea purpurea Ginkgo biloba Valeriana officinalis

Comparison of Two Advection-Diffusion Methods for Tephra Transport in Volcanic Eruptions

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Communications in Computational Physics 2011年第5期9卷 1323-1334页

作者： Kae Tsunematsu Bastien Chopard Jean-Luc falcone Costanza Bonadonna Department of Mineralogy University of Geneva13 Rue des Maraichers1205 GeneveSwitzerland Department of Computer Science University of Geneva7 Route de Drize1227 CarougeSwitzerland

In order to model the dispersal of volcanic particles in the atmosphere and their deposition on the ground,one has to simulate an advection-diffusionsedimentation process on a large spatial *** we compare a Lattice Boltzmann and a Cellular Automata *** results show that for high Peclet regimes,the cellular automata model produce results that are as accurate as the lattice Boltzmann model and is computationally more effective.

关键词： Cellular automata lattice Boltzmann tephra transport advection-diffusion computational efficiency

Long-Time Turbulence Model Deduced from the Navier-Stokes Equations

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Chinese Annals of Mathematics,Series B 2015年第5期36卷 883-894页

作者： roger LEwANDOwSKI IRMAR and Fluminance Team University of Rennes 1 and INRIA Campus Beaulieu

The author shows the existence of long-time averages to turbulent solutions of the Navier-Stokes equations and determines the equations satisfied by them, involving a Reynolds stress that is shown to be dissipative.

关键词： Navier-Stokes equations weak solutions Turbulence modeling Reynolds stress

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.w.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Highly efficient and automated extraction of DNA from human remains using a modified EZ1 protocol

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Forensic Sciences Research 2021年第1期6卷 59-66页

作者： Anna Barbaro Sasha Samar Giacomo falcone Angelo La Marca Department of Forensic Genetics Studio Indagini Mediche E Forensi(SIMEF)Reggio CalabriaItaly

Bones and teeth often represent the only sources of DNA available for identifying human *** in bones and teeth is generally better preserved than that in soft tissues because of the presence of hard connective tissue with a high level of *** of the extensive mineralisation,the choice of an efficient DNA extraction procedure is important to minimise the sampling of a high level of minerals and to remove polymerase chain reaction(PCR)*** protocols are available for DNA extraction from bones and teeth as part of the Qiagen EZ1 DNA Investigator Kit using the EZ1 Advanced XL automated purification *** improve the efficiency of DNA extraction from skeletal remains,the present study focuses on a modification to these already available *** this study,different bones and teeth collected between 1 and 50 years after death were subjected to DNA extraction using the standard EZ1 protocol,a supplementary protocol,and a modified *** modified approach included a decalcification step,whereas the Qiagen protocols worked directly on non-decalcified *** all three procedures,150 mg samples were used for DNA *** evaluated the quantity of DNA recovered from samples,the presence of any PCR inhibitors co-extracted,the level of DNA degradation,the quality of short tandem repeat(STR)profiles,and the reproducibility of the modified *** compared with the other protocols,the modified protocol resulted in the best recovery of DNA that was free of PCR ***,the STR profiles were reliable and of high *** our opinion,the decalcification step increases DNA recovery by softening tissues,which allows lysis solutions to act more ***,the use of two lysis solutions and the variation added to the EZ1 purification step allow for DNA recovery with quality and quantity superior to those of the previously available Qiagen-based *** findings may be helpful solutions to t

关键词： Forensic sciences forensic genetics DNA extraction bone tooth EZ1 automation

Atrial fibrillation in the elderly

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Journal of Geriatric Cardiology 2005年第2期2卷 68-73页

作者： roger Kerzner Michael w. Rich Cardiovascular Division

Atrial fibrillation (AF) is an extremely common condition in the elderly, with increasing prevalence around the world as the population ages. AF may be associated with serious health consequences, including stroke, heart failure, and decreased quality of life, so that careful management of AF by geriatric health care providers is required. with careful attention to anticoagulation therapy, and prudent use of medications and invasive procedures to minimize symptoms, many of the adverse health consequences of AF can be prevented.

关键词： atrial fibrillation antithrombotic rhythm control rate control elderly