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Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells

World Journal of Stem Cells 2020年第11期12卷 1410-1428页

作者： Petra Jagust Sonia Alcala bruno sainz jr Christopher Heeschen Patricia Sancho Molecular Pathology Programme Spanish National Cancer Research Centre(CNIO)Madrid 28029Spain Department of Biochemistry Autónoma University of MadridInstituto de Investigaciones Biomédicas"Alberto Sols"CSIC-UAMMadrid 28029Spain Center for Single-Cell Omics&Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai Jiao Tong University School of MedicineShanghai 200025China Hospital Universitario Miguel Servet IIS AragonZaragoza 50009Spain

BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different CSCs,including pancreatic CSCs,favor mitochondrial metabolism as their dominant energy-producing pathway.This suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species(ROS)and maintain stemness in oxidative CSCs.Since glutathione metabolism is critical for normal stem cell function and CSCs from breast,liver and gastric cancer show increased glutathione content,we hypothesized that pancreatic CSCs also rely on this pathway for ROS detoxification.AIM To investigate the role of glutathione metabolism in pancreatic CSCs.METHODS Primary pancreatic cancer cells of patient-derived xenografts(PDXs)were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in stemness.Real-time polymerase chain reaction(PCR)was used to validate RNAseq results involving glutathione metabolism genes in adherent vs spheres,as well as the expression of pluripotency-related genes following treatment.Public TCGA and GTEx RNAseq data from pancreatic cancer vs normal tissue samples were analyzed using the webserver GEPIA2.The glutathione-sensitive fluorescent probe monochlorobimane was used to determine glutathione content by fluorimetry or flow cytometry.Pharmacological inhibitors of glutathione synthesis and recycling[buthionine-sulfoximine(BSO)and 6-Aminonicotinamide(6-AN),respectively]were used to investigate the impact of glutathione depletion on CSC-enriched cultures.Staining with propidium iodide(cell cycle),Annexin-V(apoptosis)and CD133(CSC content)were determined by flow cytometry.Self-renewal was assessed by sphere formation assay and response to gemcitabine treatment was used as a readout for chemoresistance.RESULTS Analysis of our previously published RNAseq dataset E-MTAB-3808 revealed upregulation of genes involved in

关键词： Pancreatic cancer Cancer stem cells Glutathione Self-renewal Chemoresistance Redox

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Capsule endoscopy and panendoscopy:A journey to the future of gastrointestinal endoscopy

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World Journal of Gastroenterology 2024年第10期30卷 1270-1279页

作者： bruno Rosa JoséCotter Department of Gastroenterology Hospital da Senhora da OliveiraGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal ICVS/3B's PT Government Associate LaboratoryBraga 4710-057Portugal

In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturized devices to evaluate the small bowel and colon[pan-intestinal capsule endoscopy(PCE)],makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders.This technology is expected to identify which patients will require conventional invasive endoscopic procedures(colonoscopy or balloon-assisted enteroscopy),based on the lesions detected by the capsule,i.e.,those with an indication for biopsies or endoscopic treatment.The use of PCE in patients with inflammatory bowel diseases,namely Crohn’s disease,as well as in patients with iron deficiency anaemia and/or overt gastrointestinal(GI)bleeding,after a non-diagnostic upper endoscopy(esophagogastroduodenoscopy),enables an effective,safe and comfortable way to identify patients with relevant lesions,who should undergo subsequent invasive endoscopic procedures.The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract,is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract,from mouth-to-anus,meeting the expectations of the early developers of capsule endoscopy.

关键词： Non-invasive endoscopy Panendoscopy Magnetically controlled capsule endoscopy Crohn’s disease Digestive bleeding

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Advances in Wireless,Batteryless,Implantable Electronics for Real‑Time,Continuous Physiological Monitoring

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Nano-Micro Letters 2024年第3期16卷 254-302页

作者： Hyeonseok Kim bruno Rigo Gabriella Wong Yoon Jae Lee Woon‑Hong Yeo IEN Center for Wearable Intelligent Systems and Healthcare Georgia Institute of TechnologyAtlantaGA 30332USA George W.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Georgia Tech and Emory University School of MedicineAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Institute for MaterialsInstitute for Robotics and Intelligent MachinesGeorgia Institute of TechnologyAtlantaGA 30332USA

This review summarizes recent progress in developing wireless,batteryless,fully implantable biomedical devices for real-time continuous physiological signal monitoring,focusing on advancing human health care.Design considerations,such as biological constraints,energy sourcing,and wireless communication,are discussed in achieving the desired performance of the devices and enhanced interface with human tissues.In addition,we review the recent achievements in materials used for developing implantable systems,emphasizing their importance in achieving multi-functionalities,biocompatibility,and hemocompatibility.The wireless,batteryless devices offer minimally invasive device insertion to the body,enabling portable health monitoring and advanced disease diagnosis.Lastly,we summarize the most recent practical applications of advanced implantable devices for human health care,highlighting their potential for immediate commercialization and clinical uses.

关键词： Implantable electronics Biomedical systems Batteryless devices Wireless electronics Physiological signal monitoring

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Fast synthesis of gold nanoparticles by cold atmospheric pressure plasma jet in the presence of Au+ions and a capping agent

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Plasma Science and Technology 2024年第7期26卷 108-115页

作者： Tatiana HABIB José Mauricio A.CAIUT bruno CAILLIER Laboratoire Diagnostics des Plasmas Hors Equilibre(DPHE) Universitéde ToulouseINU ChampollionAlbi 81000France Department of Chemistry The Nanomaterials and Luminescent Systems GroupFaculty of PhilosophyScience and Letters at Ribeirão PretoUniversity of São PauloRibeirão Preto-SP 14040-901Brazil

Homogeneous gold nanoparticles were synthesized under atmospheric pressure using a nonthermal helium plasma jet in a single-step process.A current power supply was used to generate the plasma discharge rich in diverse reactive species.These species induce rapid chemical reactions responsible for the reduction of the gold salts upon contact with the liquid solution.In this study,spherical and monodispersed gold nanoparticles were obtained within 5 min of plasma exposure using a solution containing gold(Ⅲ)chloride hydrate(HAuCl_(4))as a precursor and polyvinylpyrrolidone(PVP)as a capping agent to inhibit agglomerations.The formation of these metal nanoparticles was initially perceptible through a visible change in the sample's color,transitioning from light yellow to a red/pink color.This was subsequently corroborated by UVvis spectroscopy,which revealed an optical absorption in the 520-550 nm range for Au NPs,corresponding to the surface plasmon resonance(SPR)band.An investigation into the impact of various parameters,including plasma discharge duration,precursor and capping agent concentrations,was carried out to optimize conditions for the formation of well-separated,spherical gold nanoparticles.Dynamic light scattering(DLS)was used to measure the size of these nanoparticles,transmission electron microscopy(TEM)was used to observe their morphology and X-ray diffraction(XRD)was also employed to determine their crystallographic structure.The results confirm that homogeneous spherical gold nanoparticles with an average diameter of 13 nm can be easily synthesized through a rapid,straightforward,and environmentally friendly approach utilizing a helium atmospheric pressure plasma.

关键词： gold nanoparticles non-thermal plasma jet helium DBD

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Are we close to using Alzheimer blood biomarkers in clinical practice?

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Neural Regeneration Research 2024年第12期19卷 2583-2585页

作者： bruno P.Imbimbo Simone Lista Camillo Imbimbo Robert Nisticò Department of Research&Development Chiesi FarmaceuticiParmaItaly i+HeALTH Strategic Research Group Department of Health SciencesMiguel de Cervantes European University(UEMC)ValladolidSpain Department of Brain and Behavioral Sciences University of PaviaPaviaItaly School of Pharmacy University of Rome“Tor Vergata”RomeItaly Laboratory of Pharmacology of Synaptic Plasticity EBRI Rita Levi-Montalcini FoundationRomeItaly

Alzheimer's disease(AD) is a progressive neurodegenerative disease histologically characterized by the presence of extraneuronal plaques,mainly formed by the 42-aminoacid isoform of amyloid-(Aβ_(1-42)),and by intraneuronal neurofibrillary to ngles,mainly formed by the tau protein and its hyperphosphorylated isoforms(p-tau).AD is the most common cause of dementia,with an estimated lifetime risk of about 1 in 10 for men and 1 in 5 for women.

关键词： Alzheimer tau Aβ

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Planar matrices and arrays of Feynman diagrams

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Communications in Theoretical Physics 2024年第3期76卷 15-32页

作者： Freddy Cachazo Alfredo Guevara bruno Umbert Yong Zhang Perimeter Institute for Theoretical Physics WaterlooON N2L 2Y5Canada Department of Physics and Astronomy University of WaterlooWaterlooON N2L 3G1Canada CECs Valdivia y Departamento de Física Universidad de ConcepciónCasilla 160-CConcepciónChile Center for the Fundamental Laws of Nature Society of Fellows and Black Hole InitiativeHarvard UniversityCambridgeMA 02138United States of America Department of Applied Mathematics Western UniversityLondonON N6A 5B7Canada CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesNo.19A Yuquan RoadBeijing 100049China

Recently,planar collections of Feynman diagrams were proposed by Borges and one of the authors as the natural generalization of Feynman diagrams for the computation of k=3 biadjoint amplitudes.Planar collections are one-dimensional arrays of metric trees satisfying an induced planarity and compatibility condition.In this work,we introduce planar matrices of Feynman diagrams as the objects that compute k=4 biadjoint amplitudes.These are symmetric matrices of metric trees satisfying compatibility conditions.We introduce two notions of combinatorial bootstrap techniques for finding collections from Feynman diagrams and matrices from collections.As applications of the first,we find all 693,13612 and 346710 collections for(k,n)=(3,7),(3,8)and(3,9),respectively.As applications of the second kind,we find all90608 and 30659424 planar matrices that compute(k,n)=(4,8)and(4,9)biadjoint amplitudes,respectively.As an example of the evaluation of matrices of Feynman diagrams,we present the complete form of the(4,8)and(4,9)biadjoint amplitudes.We also start a study of higher-dimensional arrays of Feynman diagrams,including the combinatorial version of the duality between(k,n)and(n-k,n)objects.

关键词： Feynman diagrams biadjoint amplitudes tropical Grassmannian

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Dislocation of primary total hip arthroplasty:Analysis of risk factors and preventive options

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World Journal of Orthopedics 2024年第6期15卷 501-511页

作者： Dario Regis Mattia Cason bruno Magnan Department of Orthopedic and Trauma Surgery Integrated University HospitalVerona 37126VenetoItaly

Total hip arthroplasty(THA)is one of the most successful elective operations in orthopedic surgery for improving pain and functional disability in patients with end-stage joint disease.However,dislocation continues to be a troublesome complication after THA,as it is a leading cause of revision and is associated with substantial social,health,and economic costs.It is a relatively rare,usually early occurrence that depends on both the patients’characteristics and the surgical aspects.The most recent and important finding is the special attention to be given preoperatively to spinopelvic mobility,which is closely related to the incidence of dislocation.Consequently,clinical and radiographic assessment of the lumbar spine is mandatory to identify an altered pelvic tilt that could suggest a different positioning of the cup.Lumbar spinal fusion is currently considered a risk factor for dislocation and revision regardless of whether it is performed prior to or after THA.Surgical options for its treatment and prevention include the use of prostheses with large diameter of femoral head size,dual mobility constructs,constrained liners,and modular neck stems.

关键词： Dislocation Total hip arthroplasty Revision surgery Review Risk factors Complication

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Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis

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Neural Regeneration Research 2024年第8期19卷 1768-1771页

作者： Federica Azzolini Ettore Dolcetti Antonio bruno Valentina Rovella Diego Centonze Fabio Buttari Unit of Neurology IRCCS NeuromedPozzilliItaly Department of System Medicine University of Tor VergataRomeItaly Synaptic Immunopathology Lab Department of Systems MedicineTor Vergata UniversityRomeItaly

In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.

关键词： disease-modifying behaviour endocannabinoid system long-term potentiation multiple sclerosis neuroplasticity neuroprotection physical exercise synaptopathy

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Advancements,strategies,and prospects of solid oxide electrolysis cells(SOECs):Towards enhanced performance and large-scale sustainable hydrogen production

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Journal of Energy Chemistry 2024年第7期94卷 688-715页

作者： Amina Lahrichi Youness El Issmaeli Shankara S.Kalanur bruno G.Pollet Green Hydrogen Lab(GH2Lab) Hydrogen Research Institute(HRI)Universitédu QuébecàTrois-Rivières(UQTR)3351 boulevard des ForgesTrois-RivièresQuébec G9A 5H7Canada

Solid oxide electrolysis cells(SOECs)represent a crucial stride toward sustainable hydrogen generation,and this review explores their current scientific challenges,significant advancements,and potential for large-scale hydrogen production.In SOEC technology,the application of innovative fabrication tech-niques,doping strategies,and advanced materials has enhanced the performance and durability of these systems,although degradation challenges persist,implicating the prime focus for future advancements.Here we provide in-depth analysis of the recent developments in SOEC technology,including Oxygen-SOECs,Proton-SOECs,and Hybrid-SOECs.Specifically,Hybrid-SOECs,with their mixed ionic conducting electrolytes,demonstrate superior efficiency and the concurrent production of hydrogen and oxygen.Coupled with the capacity to harness waste heat,these advancements in SOEC technology present signif-icant promise for pilot-scale applications in industries.The review also highlights remarkable achieve-ments and potential reductions in capital expenditure for future SOEC systems,while elaborating on the micro and macro aspects of sOECs with an emphasis on ongoing research for optimization and scal-ability.It concludes with the potential of SOEC technology to meet various industrial energy needs and its significant contribution considering the key research priorities to tackle the global energy demands,ful-fillment,and decarbonization efforts.

关键词： Solid oxide electrolysis cells Proton-SOECs Oxygen-SoECs Hybrid-SOECs Intermediate-high temperature electrolysers Hydrogenproduction

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Physical activity volume,frequency,and intensity:Associations with hypertension and obesity over 21 years in Australian women

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Journal of Sport and Health Science 2024年第5期13卷 631-641页

作者： Gregore I.Mielke Ding Ding Shelley E.Keating bruno P.Nunes Ruth Brady Wendy J.Brown School of Public Health The University of QueenslandBrisbaneQLD 4006Australia Sydney School of Public Health Faculty of Medicine and HealthThe University of SydneySydneyNSW 2006Australia The Charles Perkins Centre The University of SydneySydneyNSW 2006Australia School of Human Movement and Nutrition Sciences The University of QueenslandBrisbaneQLD 4072Australia School of Nursing Federal University of PelotasPelotasRio Grande do Sul 96010-610Brazil Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4226Australia

Background:Optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not known.The overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 years.Specifically,we investigated whether,for the same weekly volume of PA,the number of sessions(frequency)and vigorousness of PA(intensity)were associated with a reduction in the occurrence of hypertension and obesity in women.Methods:Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed(n=20,588;12%-16%with a Bachelor's or higher degree).Self-reported PA,hypertension,height,and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/2021.Generalized Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume(metabolic equivalent min/week)(none;33-499;500-999;≥1000,weekly frequency(none;1-2 times;3-4times;5-7 times;≥8 times),and the proportion of vigorous PA to total volume of PA(none;0%;1%-33%;34%-66%;67%-100%)with odds of hypertension and obesity from 2000 to 2021.Results:The cumulative incidence of hypertension was 6%in the 1973-1978 and 23%in the 1946-1951 cohort;27%of women in the 1973-1978;and 15%in the 1946-1951 cohort developed obesity over the period.Overall,a higher volume of PA was associated with reduced odds of hypertension and obesity.When the volume of PA was considered,the odds of hypertension did not vary according to the frequency or intensity of PA.However,increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obe sity.Conclusion:PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and obesity.Incorporating more sessions,particularly of vigorous-intensity PA,may provide extra benefits for the prevention of obesity.

关键词： Physical activity Frequency Intensity Incidences Epidemiology Women

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