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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Scale dependency of Liolaemus lizards＇ home range in response to different environmental variables

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Current Zoology 2016年第6期62卷 521-530页

作者： Oscar Anibal STELLATELLI Carolina BLOCK Debora Lina MORENO-AZOCAR Laura Estela vega Juan pablo ISACCH Felix Benjamin CRUZ Laboratorio de Vertebrados Departamento de Biologia Instituto de Investigaciones Marinas y Costeras (IIMyC) CONICET-Facultad de Ciencias Exactas y Naturales Universidad Nacional de Mar del Plata. Defin Funes 3250 (B7602AYJ) Mar del Plata Buenos Aires Argentina Instituto de Investigaciones en Biodiversidad y Medioambiente (INIBIOMA) CONICET-Universidad Nacional del Comahue. Quintral 1250 (8400) San Carlos de Bariloche Rio Negro Argentina.

Animal habitat-use patterns cannot be isolated from scale issues. Consequently, multi-scale studies provide a complete characterization of ecological patterns that can further explain the observed variation. Liolaemus constitutes the world＇s second most speciose lizard genus. In this study, we assessed the relationships between home range size and environmental variables at 3 different spatial scales. The study at a local and regional scale was focused on the habitat specialist Liolaemus multimaculatus. The lizard＇s home range was calculated using the minimum convex polygon method in populations from grassland sites of the coastal sand dunes of the Argentinean Pampas under 2 different conditions, with or without forestations of Acacia Iongifolia. On the other hand, at a geographical scale we considered the evolutionary implications of 20 species of Liolaemus. Home range size, phylogeny, ecological, environmental, and climatic data were ob- tained from the literature and remote sensing. L. multimaculatus home range varied from 12.66 to 570.00 m. Regionally, this species had smaller home ranges in forested habitats （X： 94.02 m2） com- pared with the non-forested sites （X： 219.78m2）. Habitat structure, vegetation types, and food availability would explain the space use at finer scales. When the 20 species of Liolaernus were considered, high mean air temperature and broad thermal amplitudes showed an inverse relationship with home range size. Neither net primary productivity nor phylogeny was good predictors for home range variation at geographical scale. This study highlights the scale dependence of the explicative capability of a set of environmental and intrinsic variables on home range patterns.

关键词： environmental factors home range Liolaemus lizard scales

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Supervised vs home-based exercise program in kidney transplant recipients: A pilot pragmatic non-randomized study

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World Journal of Transplantation 2024年第4期14卷 123-132页

作者： Anna Crepaldi Giovanni Piva Nicola Lamberti Michele Felisatti Luca Pomidori Yuri Battaglia Fabio Manfredini Alda Storari pablo Jesús López-Soto Unit of Nephrology University Hospital of FerraraFerrara 44121Emilia-RomagnaItaly Department of Nursing Instituto Maimónides de Investigación Biomédica de CórdobaCordoba 14004AndalusiaSpain Department of Neuroscience and Rehabilitation University of FerraraFerrara 44121Emilia-RomagnaItaly Esercizio Vita Medical Fitness Ferrara 44124Emilia-RomagnaItaly Department of Medicine University of VeronaVerona 37100VenetoItaly Department of Nursing Maimonides Biomedical Research Institute of CordobaUniversity of CordobaReina Sofía University HospitalCordoba 14004AndalusiaSpain

BACKGROUND Although the benefits of exercise for kidney transplant recipients(KTRs)have been widely demonstrated,these patients experience several barriers in undertaking a structured exercise program in hospital and non-hospital *** To compare the effects of a supervised moderate-intensity gym-based intervention with a home-based low-intensity walking program on exercise capacity in *** KTRs were asked to choose between two six-month *** first group performed a low-intensity interval walking intervention at home-based exercise intervention (HBex). The second group performed a supervised training program at an adapted physical activitygym (Sgym), including aerobic and resistance training. The outcomes, collected at baseline and at the end of theprograms, included the 6-minute walking test, the peak oxygen consumption (VO_(2)peak) during a treadmill test,the 5-time sit-to-stand test, and blood *** patients agreed to participate and self-selected into the HBex (n = 9) and Sgym (n = 8) groups. Twopatients in the Sgym group dropped out because of familial problems. At baseline, patients in the HBex group weresignificantly older and had lower walking distance, VO_(2)peak, and lower limb strength. Primary outcome changeswere significantly greater in the HBex group than in the Sgym group (52 ± 23 m vs 8 ± 34;P = 0.005). No othersignificant differences between groups were observed. Both groups improved most of the outcomes in the withingroupcomparisons, with significant variations in VO_(2) ***-month moderate-intensity supervised or low-intensity home-based training programs effectively improvedexercise capacity in KTRs. Gym-based programs combine aerobic and resistance training;however, in-homewalking may be proposed for frail KTRs.

关键词： Exercise Transplantation Walking Training Nephrology Kidney disease

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Carpal Tunnel Syndrome: A Marker for Amyloidosis

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World Journal of Neuroscience 2024年第3期14卷 92-101页

作者： Luciana León Cejas Miguel Saucedo Mayra Aldecoa Gustavo Teruya Fabricio Silva Alvaro Muratore Gonzalo Viollaz Cintia Marchesoni Ana Pardal pablo Dezanzo Alejandro Iotti Ricardo Reisin Neurology Department Hospital Britnico de Buenos Aires Buenos Aires Argentina Orthopedics Department Hospital Britnico de Buenos Aires Buenos Aires Argentina Pathology Department Hospital Britnico de Buenos Aires Buenos Aires Argentina

Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyloid deposition in idiopathic CTS and its systemic impact. Methods: We retrospectively evaluated patients with CTS between September 2019 to January 2020. Samples from the anterior carpal ligament were pathologically evaluated and amyloid deposition was confirmed by apple-green birefringence on polarized light using Congo red stain. When amyloid was detected we performed genetic testing for transthyretin variants (ATTRv), immunofixation electrophoresis in serum and urine for light chains and multidisciplinary evaluation. Results: Thirty consecutive patients were included, 19 women, 11 men, mean age 70 years old (range 42 - 89 years). We identified 3 patients (10%) with amyloid deposits (mean age: 78.6 years, 2 men, 1 woman). Genetic testing for ATTRv and light chains studies were negative. During follow-up: The first patient required aortic valve replacement. The second patient developed progressive cardiac failure with syncopal episodes, atrioventricular block and atrial fibrillation and required a pacemaker and anticoagulation. The third patient had unexplained chronic edemas. The cardiac evaluation in all 3 patients revealed left ventricular hypertrophy and myocardial uptake (Perugini Score > 2) in their nuclear bone scintigraphies with technetium pyrophosphate. Two patients were treated with tafamidis and one patient died due to refractory cardiac insufficiency. Discussion: Our findings underline the importance of investigating amyloidosis in idiopathic CTS. The identification of deposits allows early diagnosis of cardiac amyloidosis leading to timely intervention and treatment.

关键词： Carpal Tunnel Amyloid Transthyretin Amyloid Cardiac Transthyretin Variants Light Chains

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球腔内低雷诺数流体中颗粒输运研究进展

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力学学报 2024年第5期56卷 1284-1296页

作者：孙壮陈高峰胡安˙德˙巴勃罗蒋玺恺中国科学院力学研究所非线性力学国家重点实验室北京100190 中国科学院大学工程科学学院北京100049 芝加哥大学普利兹克分子工程学院美国芝加哥60637 阿贡国家实验室材料科学部美国莱蒙特60439

受限环境下低雷诺数流体中的颗粒输运与生物、医药、化工和能源等应用密切相关.近年来,球腔内低雷诺数流体中的颗粒输运引起了广泛关注,它在细胞内生命活动和微流控封装技术中发挥着关键作用.为了掌握颗粒输运规律、揭示微观力学机理,... 详细信息

受限环境下低雷诺数流体中的颗粒输运与生物、医药、化工和能源等应用密切相关.近年来,球腔内低雷诺数流体中的颗粒输运引起了广泛关注,它在细胞内生命活动和微流控封装技术中发挥着关键作用.为了掌握颗粒输运规律、揭示微观力学机理,各国学者进行了广泛的理论、数值和实验研究,取得了一系列成果.本文将梳理当前的研究进展,分别从理论模型、数值模拟和实验研究三方面,介绍关于球腔内低雷诺数流体中颗粒输运的重要工作.理论模型方面,主要工作包括刚性无滑移壁面、边界滑移和可变形壁面等情况下单个及多个颗粒输运的研究;数值模拟方面,重要工作包括模拟不同形状颗粒在静止与旋转球腔内的输运,研究颗粒的水动力迁移率与运动轨迹;实验研究方面,相关工作包含水液滴内颗粒三维轨迹、扩散系数的观测,以及利用球腔内颗粒布朗运动来计算受限环境性质的相关研究.通过总结相关成果,旨在为微纳尺度流动与颗粒输运领域的专家学者提供参考.

关键词：低雷诺数流体颗粒输运限域效应

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ACORDE Project:Adaptable Residential Buildings for a New Social Framework

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Journal of Civil Engineering and Architecture 2024年第3期18卷 118-133页

作者： pablo Emilio Branchi Acorde espacios adaptablesS.L.y UPNASpain

ACORDE project seeks to maximize buildings´flexibility,conceiving a residential building made of legally independent functional units that can be connected to or disconnected from each other with easy,plug-in facilities,in a way that permits to purchase exactly what the user need,as well as allows future changes for buildings to be adapted to the needs of their occupants,the user decides how to best utilize the space by acquiring or separating functional units along the *** this to be possible,in addition to the legally independent modules concept,a diaphanous and very well organized structure is projected as well as a very solid and efficient envelope to ensure durability and minimal *** efficient occupancy of space leads to an optimal use of energy.

关键词： Adaptability flexibility demographic changes end-uses plug&play

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Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

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World Journal of Transplantation 2024年第2期14卷 126-134页

作者： Gabriel Lazzarotto-da-Silva Leandro A Scaffaro Mauricio Farenzena Lucas Prediger Rafaela K Silva Flávia Heinz Feier Tomaz J M Grezzana-Filho pablo D Rodrigues Alexandre de Araujo Mario Reis Alvares-da-Silva Roberta C Marchiori Cleber Rosito Pinto Kruel Marcio Fernandes Chedid Department of Liver Transplant and Hepatobiliary Surgery Unit Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Department of Interventional Radiology Unit Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Department of Gastroenterology and Hepatology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long *** therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting *** largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the *** To compare the outcomes of TACE and TAE in patients with HCC awaiting *** All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were *** patients underwent LRT with either TACE or *** patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment *** choice of LRT for each HCC nodule was determined by a multidisciplinary *** primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse *** the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also *** Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was simila

关键词： Hepatocellular carcinoma Transarterial embolization Transarterial chemoembolization Liver transplantation Locoregional therapy Bridging

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Main environmental variables influencing the abundance of plant species under risk category

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Journal of Forestry Research 2022年第4期33卷 1209-1217页

作者： pablo Antúnez División de Estudios de Posgrado Universidad de la Sierra Juárez68725 Oax.México

Determining climatic and physiographic variables in Mexico’s major ecoregions that are limiting to biodiversity and species of high conservation concern is essential for their ***,at the national level to date,few studies have been performed with large data sets and crossconfirmation using multiple statistical ***,we used 25 endemic,rare and endangered species from 3610 sampling points throughout Mexico and 25 environmental attributes,including average precipitation for different seasons of the year,annual dryness index,slope of the terrain;and maximum,minimum and average temperatures to test our hypothesis that these species could be assessed with the same weight among all variables,showing similar indices of *** results using principal component analysis,covariation analysis by permutations,and random forest regression showed that summer precipitation,length of the frost-free period,spring precipitation,winter precipitation and growing season precipitation all strongly influence the abundance of tropical *** contrast,annual precipitation and the balance at different seasons(summer and growing season)were the most relevant variables on the temperate region *** dry areas,the minimum temperature of the coldest month and the maximum temperature of the warmest month were the most significant *** these different associations in different climatic regions could support a more precise management and conservation plan for the preservation of plant species diversity in forests under different global warming scenarios.

关键词： Correlative models Climate change Effect of topography Endemic species IUCN list Machine learning algorithms

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Influence of Angiotensin II on α₁-Adrenergic Receptors Function in Rat Aorta and Expression in Vascular Smooth Muscle Cells

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Journal of Biosciences and Medicines 2024年第4期12卷 123-134页

作者： Itzell Alejandrina Gallardo-Ortíz Juan pablo de Jesús Benítez-Garrido Santiago C. Sigrist-Flores Juan Javier López-Guerrero Enrique Hong Rafael Villalobos-Molina Unidad de Biomedicina Facultad de Estudios Superiores Iztacala Universidad Nacional Aut&#243noma de M&#233xico Tlalnepantla M&#233xico Carrera de Enfermerí a Facultad de Estudios Superiores Iztacala Universidad Nacional Aut&#243noma de M&#233xico Tlalnepantla M&#233xico Departamento de Farmacobiologí a Centro de Investigaci&#243n and de Estudios Avanzados-IPN Ciudad de M&#233xico M&#233xico Carrera de Mé dico Cirujano Facultad de Estudios Superiores Iztacala Universidad Nacional Aut&#243noma de M&#233xico Tlalnepantla M&#233xico

Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT1 and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α1-adrenergic receptors (α1-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10−5 M), and in some experiments, 5-Methylurapidil (α1A-AR antagonist), AH11110A (α1B-AR antagonist), or BMY-7378 (α1D-AR antagonist), were used to identify the α1-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α1D-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α1-ARs proteins were evaluated. α1D-AR increased at 30 and 60 min post Ang II exposure, the α1A-AR diminished from 1 to 4 h, while α1B-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α1D-AR at short times, and BMY-7378 protected α1D-AR from desensitization.

关键词： Angiotensin II α1D-AR α1-AR Expression Rat aorta Smooth Muscle Cells

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On the interaction of a donepezil-huprine hybrid with synthetic membrane models

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Neural Regeneration Research 2023年第2期18卷 333-334页

作者： pablo Zambrano Max Planck Institute of Biochemistry Cellular and Molecular BiophysicsMunichGermany

Alzheimer's disease is the most prevalent type of dementia today,discovered and described by Alois Alzheimer in *** to the World Alzheimer Report 2021,75%of people with dementia worldwide are undiagnosed,equivalent to 41 million people(Gauthier et al.,2021).With each passing year,the number of people affected by these diseases is increasing,and the estimates of suffering from them in the future are growing.

关键词： Alzheimer diseases

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