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Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

Neural Regeneration Research 2023年第6期18卷 1196-1202页

作者： Instituto de Salud carlos III Irene Villalón-García Suleva Povea-cabello mónicaÁlvarez-córdoba marta Talaverón-Rey Juan mSuárez-Rivero Alejandra Suárez-carrillo manuel munuera-cabeza Diana Reche-López Paula cilleros-Holgado Rocío Piñero-Pérez JoséA.Sánchez-Alcázar centro Andaluz de Biología del Desarrollo(cABD-cSIc-Universidad Pablo de Olavide de Sevilla) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos IIISevillaSpain

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders.mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

关键词： 4-hidroxynonenal ferroptosis iron lipid peroxidation lipofuscin neurodegeneration neurodegeneration with brain iron accumulation oxidative stress PLA2G6-associated neurodegeneration

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Precision medicine in pantothenate kinase-associated neurodegeneration

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Neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： mónica álvarez-córdoba marina Villanueva-Paz Irene Villalón-García Suleva Povea-cabello Juan m.Suárez-Rivero marta Talaverón-Rey Javier Abril-Jaramillo Ana Belén Vintimilla-Tosi José A.Sánchez-Alcázar centro Andaluz de Biología del Desarrollo(cABD-cSIc-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ centro de Neurología Avanzada centro civet

Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal ganglia.The predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal degeneration.Among the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis pathway.currently there is no effective treatment to prevent the inexorable course of these disorders.The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN.Recently,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative stress.In addition,PKAN fibroblasts showed a morphological senescence-like phenotype.Interestingly,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression.However,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein.The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts.Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations.Fibroblasts and induced neuron

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

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Neurovascular unit on a chip: the relevance and maturity as an advanced in vitro model

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Neural Regeneration Research 2024年第6期19卷 1165-1166页

作者： Sujey Palma-Florez Anna Lagunas mònica mir Nanobioengineering Group Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST) Department of Electronics and Biomedical Engineering University of Barcelona cIBER-BBN ISCIII

The brain is a high-energy demanding organ, consuming around 20% of the metabolic energy generated. To fulfill this demand, cerebral blood flow(cBF) supplies oxygen and glucose continuously through the intricate network of cerebral blood vessels. Although for many years brain activity and blood flow were conceived as independent processes, mRI-based functional brain imaging demonstrated that there is a coupling between them,

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Efficacy of acupuncture on cancer pain:A systematic review and meta-analysis

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Journal of Integrative medicine 2024年第3期22卷 235-244页

作者： miguel Faria mónica Teixeira maria João Pinto Paulo Sargento Núcleo de Investigação em ciências e Tecnologias da Saúde Instituto Politécnico da Lusofonia1950-396 LisboaPortugal clínica São João de Deus 1700-048 LisboaPortugal REQUImTE/LAQV(Rede de Química e Tecnologia/Laboratório Associado para a Química Verde) Instituto Superior de EngenhariaInstituto Politécnico do Porto4051-401 PortoPortugal Hospital SOERAD 2560-312 Torres VedrasPortugal centro de Estudos Avançados em Direito“Francisco Suarez ”1749-024 LisboaPortugal

Background:Pain associated with cancer is one of the greatest causes of reduced quality of life in patients.Acupuncture is one of the treatments used to address this issue,with the great advantage of having little or no side effects,especially when compared with pharmacological pain-killers.Objective:The aim of this systematic review and meta-analysis was to evaluate the current evidence regarding the efficacy of acupuncture for cancer pain.Search strategy:Six electronic databases(Pubmed,EBScO,cochrane Library,Scielo,b-On and Scopus)were searched for relevant articles about pain relief in cancer patients from their beginning until 2022using meSH terms such as“acupuncture,”“electroacupuncture,”“ear acupuncture,”“acupuncture analgesia,”“oncological pain,”and“cancer pain.”Inclusion criteria:Studies included were randomized controlled trials(RcTs)where acupuncture was compared with no treatment,placebo acupuncture or usual care.Data extraction and analysis:Three independent reviewers participated in data extraction and evaluation of risk of bias,and a meta-analysis was conducted.The primary outcome was pain intensity,measured with the visual analog scale,numeric rating scale,or brief pain inventory.Secondary outcomes also assessed were quality of life,functionality,xerostomia,pain interference,and analgesic consumption.Results were expressed as standardized mean difference(SmD)with 95%confidence interval(cI).Results:Sixteen RcTs with a total of 1124 participants were included in the meta-analysis,with the majority of the studies presenting a low or unclear risk of bias.Acupuncture was more effective in reducing pain than no treatment(SmD=–0.90,95%cI[–1.68,–0.12]),sham acupuncture(SmD=–1.10,95%cI[–1.59,–0.61])or usual care(SmD=–1.16,95%cI[–1.38,–0.93]).conclusion:The results of this study suggest that acupuncture may be an effective intervention to reduce pain associated with cancer.Despite some limitations due to the low quality and small sample size of some included studies,as well as the different types and stages

关键词： Acupuncture cancer pain meta-analysis Systematic review

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Association of congenital Heart Defects (cHD) with Factors Related to maternal Health and Pregnancy in Newborns in Puerto Rico

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congenital Heart Disease 2024年第1期19卷 19-31页

作者： Yamixa Delgado caliani Gaytan Naydi Perez Eric miranda Bryan colón morales mónica Santos Biochemistry&Pharmacology Department San Juan Bautista School of MedicineCaguas00726Puerto Rico Hispanic Alliance for clinical and Translational Research University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico Department of Internal medicine University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BmI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(cHD)during neonatal development.methods:Using the comprehensive System of Vigilance and Surveillance of congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with cHD between 2016 and 2020.Our assessment encompassed a range of variables,including maternal age,gestational age,BmI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of preeclampsia.Results:A cohort of 673 patients was included in our study.The average maternal age was 26 years,within a range of 22 to 32 years.The mean gestational age measured 39 weeks,with a median span of 38 to 39 weeks.Of the 673 patients,274(41%)mothers gave birth to neonates diagnosed with cHD.Within this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BmI,whereas 126 displayed a normal BmI.conclusion:We identiﬁed a statistically signiﬁcant correlation between pre-gestational diabetes mellitus and the occurrence of cHD.However,our analysis did not show a statistically signiﬁcant association between maternal BmI and the likelihood of cHD.These results may aid in developing effective strategies to prevent and manage cHD in neonates.

关键词： congenital heart defects(cHD) obesisty maternal health diabetes body mass index(BmI)

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Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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marine Life Science & Technology 2024年第2期6卷 252-265页

作者： carmen González‑Fernández miguel A.García‑Álvarez Alberto cuesta Department of cell Biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

Th17 is a lymphocyte T helper(Th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-17.This crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six members.Although the biology of fish Th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been limited.Thus,our aim was to identify and characterize the IL-17R repertory and regulation in the two main mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human orthologues.All of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or intestine.In leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most stimulants.Interestingly,in vivo nodavirus infection resulted in alterations on the transcription of il17 receptors.While nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead seabream.Our data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： Th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture

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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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military medical Research 2024年第2期11卷 228-267页

作者： miguel A.Ortega Oscar Fraile-martinez cielo García-montero Sergio Haro miguel Ángel Álvarez-mon Diego De Leon-Oliva Ana m.Gomez-Lahoz Jorge monserrat mar Atienza-Pérez David Díaz Elisa Lopez-Dolado melchor Álvarez-mon Department of medicine and medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y cajal Institute of Sanitary Research(IRYcIS) 28034 MadridSpain Department of Psychiatry and mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(ScI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after ScI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of ScI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(ScI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

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A Rapid Parameter of Enzyme-Treated cellulosic material Revealed by Reducing Sugar Release

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Journal of Renewable materials 2024年第3期12卷 539-551页

作者： Verônica Távilla Ferreira Silva Adriane maria Ferreira milagres Departamento de Biotecnologia Escola de Engenharia de LorenaUniversidade de São PauloLorenaSP12602-810Brazil

This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.

关键词： Endoglucanase xylanase cellulose fiber pulp synergism

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Solar-driven cO_(2) conversion to methane and methanol using different nanostructured cu_(2)O-based catalysts modified with Au nanoparticles

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Journal of Energy chemistry 2024年第4期91卷 287-298页

作者： João Angelo Lima Perini Lilian D.moura Torquato Juliana Fde Brito Gustavo A.Andolpho mateus A.Gonçalves Leonardo D.De Angelis Lucas D.Germano Susana I.córdoba de Torresi Teodorico c.Ramalho maria V.Boldrin Zanoni São Paulo State University(UNESP) Institute of ChemistryRua Prof.Francisco Degni55AraraquaraSP 14800-060Brazil National Institute of Alternative Technologies for Detection Toxicological Evaluation and Removal of Micropollutants and Radioactive Substances(INCT-DATREM)São Paulo State University(UNESP)Institute of ChemistryRua Prof.Francisco Degni55AraraquaraSP 14800-060Brazil Laboratory of molecular modelling Department of ChemistryNatural Sciences InstituteFederal University of LavrasLavrasMG 37200-900Brazil Department of chemistry Faculty of ScienceUniversity of Hradec KrálovéHradec Králové50003Czech Republic Instituto de Química Universidade de São PauloAv.Prof.Lineu Prestes 74805508-080São PauloSPBrazil

This work describes the use of TiO_(2)nanotubes-based electrodes(TNT)modified with cu_(2)O nanostructures and gold nanoparticles for the photoelectroreduction of cO_(2)to produce value-added compounds.A thin layer of polydopamine was used as both an adherent agent and an electron transfer mediator,due to itsπ-conjugated electron system.The highest production yield was achieved using a TNT@PDA/Nc/Au40%electrode,with Faradaic efficiencies of 47.4%(110.5μm cm^(-2))and 27.8%(50.4μm cm^(-2))for methanol and methane,respectively.The performance of the photoelectrodes was shown to be cu_(2)O facet-dependent,with cubic structures leading to greater conversion of cO_(2)to methanol(43%)and methane(27%),compared to the octahedral morphology,while a higher percentage of metallic gold on the nanostructured cu_(2)O surface was mainly important for cH4production.Density functional theory(DFT)calculations supported these findings,attributing the superior photoelectrocatalytic performance of the TNT@PDA/Nc/Au40%electrode for cH4generation to the formation of an OcH3intermediate bonded to Au atoms.Studies using isotope-labeling and analysis by gas chromatograph-mass(Gc-mS)demonstrated that13cO_(2)was the source for photoelectrocatalytic generation of13cH3OH and13cH313cH2OH.

关键词： cu_(2)O nanocubes Photoelectrocatalysis Polydopamine cO_(2) photoelectroreduction DFT calculations

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Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

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World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan Pablo Stefanolo Verónica Segura martina Grizzuti Abel Heredia Isabel comino Ana Florencia costa Roberto Puebla maría Paz Temprano Sonia Isabel Niveloni Gabriel de Diego maría E Oregui Edgardo Gustavo Smecuol mauricio c de marzi Elena F Verdú carolina Sousa Julio césar Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BAcKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIm To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(ceD)patients following their usual GFD.mETHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled ceD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLc,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(cSI);(3)ceD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(mples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.compared with the run-in period,the proportion of symptomatic patients(cSI>38)in the AN-PEP arm was significantly lower(Pchanges in specific serologies.cONcLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-P

关键词： celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

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