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

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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

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-de Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina department of Laboratory Medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese Medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

Fecal marker levels as predictors of need for endoscopic balloon dilation in Crohn's disease patients with anastomotic strictures

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World Journal of Gastroenterology 2017年第35期23卷 6482-6490页

作者： Susana Lopes Patrícia Andrade Eduardo Rodrigues-Pinto Joana Afonso Guilherme macedo Fernando Magro Gastroenterology department Faculty of MedicineHospital de Sao Joao department of Pharmacology and Therapeutics University of Porto

AIM To evaluate the accuracy and best cut-off value of fecal calprotectin(FC) and fecal lactoferrin(FL) to predict disease recurrence in asymptomatic patients presenting with anastomotic strictures. METHODS This was a longitudinal single tertiary center study based on prospectively collected data(recorded in a clinical database created for this purpose) performed between March 2010 and November 2014. Crohn's disease(CD) patients with anastomotic stricture who submitted to postoperative endoscopic evaluation were included. Stools were collected on the day before bowel cleaning for FC and FL. Endoscopic balloon dilation(EBD) was performed if the patient presented an anastomotic stricture not traversed by the colonoscope, regardless of patients' symptoms. Successful dilation was defined as passage of the colonoscope through the dilated stricture into the neotermimal *** recurrence was defined as a modified Rutgeerts score of ≥ i2 b. RESULTS In a total of 178 patients who underwent colonoscopy, 58 presented an anastomotic stricture, 86% were asymptomatic, and 48(54% male; median age of 46.5 years) were successfully dilated. Immediate success rate was 92% and no complications were recorded. FC and FL levels correlated significantly with endoscopic recurrence(P de the need for EBD in this context.

关键词： Crohn's disease Anastomotic strictures Endoscopic balloon dilation Fecal markers Po stoperative recurrence

Synthesis Gas Production from Natural Gas on Supported Pt Catalysts

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Journal of Natural Gas Chemistry 2006年第1期15卷 21-27页

作者： Mariana M. V. M. Souza Octávio R. macedo Neto Martin Schmal NUCAT/PEQ/COPPE

Auto-thermal reforming of methane, combining partial oxidation and reforming of methane with CO2 or steam, was carried out with Pt/Al2O3, Pt/ZrO2 and Pt/CeO2 catalysts, in a temperature range of 300-900℃. The auto-thermal reforming occurs in two simultaneous stages, namely, total combustion of methane and reforming of the unconverted methane with steam and CO2, with the O2 conversion of 100% starting from 450℃. For combination with CO2 reforming, the Pt/CeO2 catalyst showed the lowest initial activity at 800℃, and the highest stability over 40 h on-stream. This catalyst also presented the best performance for the reaction with steam at 800℃. The higher resistance to coke formation of the catalyst supported on ceria is due to the metal-support interactions and the higher mobility of oxygen in the oxide lattice.

关键词： methane steam reforming CO2 reforming partial oxidation auto-thermal reforming platinum catalyst ceria zirconia

Seismic performance of composite moment-resisting frames achieved with sustainable CFST members

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Frontiers of Structural and Civil Engineering 2016年第3期10卷 312-332页

作者： A. SILVA Y. JIANG L. macedo J. M. CASTRO R. MONTEIRO N. SILVESTRE department of Civil Engineering Faculty of Engineering University of Porto Porto 4099-002 Portugal Istituto Universitario di Studi Superiori di Pavia Pavia 27100 Italy IDMEC LAETA Department of Mechanical Engineering Instituto Superior Tecnico Universidade de Lisboa Lisboa 1649-004 Portugal

The main objective of the research presented in this paper is to study the bending behaviour of Concrete Filled Steel Tube （CFST） columns made with Rubberized Concrete （RuC）, and to assess the seismic performance of moment-resisting frames with these structural members. The paper describes an experimental campaign where a total of 36 specimens were tested, resorting to a novel testing setup, aimed at reducing both the preparation time and cost of the test specimens. Different geometrical and material parameters were considered, namely cross-section type, cross-section slenderness, aggregate replacement ratio, axial load level and lateral loading type. The members were tested under both monotonic and cyclic lateral loading, with different levels of applied axial loading. The test results show that the bending behaviour of CFST elements is highly dependent on the steel tube properties and that the type of infill does not have a significant influence on the flexural behaviour of the member. It is also found that Eurocode 4 is conservative in predicting the flexural capacity of the tested specimens. Additionally, it was found that the seismic design of composite moment- resisting frames with CFST columns, according to Eurocode 8, not only leads to lighter design solutions but also to enhanced seismic performance in comparison to steel frames.

关键词： concrete filled steel tubes rubberized concrete composite frames seismic performance assessment

Free amino acid content in trunk,branches and branchlets of Araucaria angustifolia(Araucariaceae)

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Journal of Forestry Research 2018年第6期29卷 1489-1496页

作者： Crizane Hackbarth Patricia Soffiatti Fla′vio Zanette Eny Iochevet Segal Floh Amanda Ferreira macedo Henrique Aparecido Laureano departamento de Fitotecnia e Fitossanitarismo Federal University of Parana(UFPR)Rua dos Funcionarios1540JuveveCuritibaPR 81531-990Brazil departamento de Botanica Federal University of Parana(UFPR)Av.Cel.Francisco H.dos Santos100Jardim das AmericasCuritibaPR 81531-980Brazil Instituto de Biociencias University of Sao PauloRua do Matao277Sao PauloSP 05508-090Brazil departamento de Estatstica Federal University of Parana(UFPR)Av.Cel.Francisco H.dos Santos100Jardim das AmericasCuritibaPR 81531-980Brazil

Araucaria angustifolia(Bertol.) O. Kuntze exhibits dimorphism in its stem structure, where the trunk is orthotropic and branches and branchlets(primary and secondary branches) are plagiotropic. These stems exhibit different behavior when used for vegetative propagation,and only segments of trunk can form a complete plant. The physiological and biochemical mechanisms that characterize these stems are still little known. The aim of this study was to describe the free amino acid profiles in trunks,branches, and branchlets of A. angustifolia. Segments of 5 cm in length were excised from young individuals below the stem apex. The needles were removed and samples were frozen and lyophilized. The determinations were made by high-performance liquid chromatography, and the results were expressed as lg/g fresh weight(FW). The trunks and branches had the highest content of total amino acids, which were 112.23 ± 20.57 lg/g FW and 111.97 ± 27.78 lg/g FW, respectively. The amino acids—glutamine, aspartate and c-aminobutyric acid and tyrosine—were noticeably higher in the three types of *** the trunk, a higher amount of asparagine and tryptophan,was also detected. Glutamic acid and glutamine were found in higher quantities in the branches. The branchlets had very low total amino acid content (30.79 ± 4.19 lg/g FW), wherein asparagine is the only amino acid not detected. Thus, it was observed that the profile of the free amino acid differs among trunks, branches, and branchlets in A. angustifolia, indicating that they perform different functions.

关键词： Brazilian pine Physiological mechanisms Stem’s dimorphism Free amino acids

Numerical Analysis of Turbulent Fluid Flow and Drag Coefficient for Optimizing the AUV Hull design

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Open Journal of Fluid Dynamics 2014年第3期4卷 263-277页

作者： Joao Victor Nunes de Sousa Antonio Roberto Lins de macedo Wanderley Ferreira de Amorim Junior Antonio Gilson Barbosa de Lima department of Mechanical Engineering Center of Sciences and TechnologyFederal University of Campina GrandeCampina GrandeBrazil ARMTEC Technology in Robotics FortalezaBrazil

Autonomous Underwater Vehicles (AUVs) are robots able to perform tasks without human intervention (remote operators). Research and development of this class of vehicles has growing, due to the excellent characteristics of the AUVs to operate in different situations. Therefore, this study aims to analyze turbulent single fluid flow over different geometric configurations of an AUV hull, in order to obtain test geometry that generates lower drag force, which reduces the energy consumption of the vehicle, thereby increasing their autonomy during operation. In the numerical analysis was used ANSYS-CFX® 11.0 software, which is a powerful tool for solving problems involving fluid mechanics. Results of the velocity (vectors and streamlines), pressure distribution and drag coefficient are showed and analyzed. Optimum hull geometry was found. Lastly, a relationship between the geometric parameters analyzed and the drag coefficient was obtained.

关键词： AUV Hull Drag Coefficient Numerical Simulation

Pseudoathletic Appearance:A Case Report in a Male

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Case Reports in Clinical Medicine 2015年第12期4卷 361-363页

作者： Joana Moreira Goncalo Gomes Pereira Mário Santos Vaz de macedo General Practice department USF CoveloPortoPortugal General Practice department USF Sem FronteirasSanta Maria da FeiraPortugal

Multiple Symmetric Lipomatosis (MSL) is a rare condition characterized by a symmetrical pattern of massive fatty deposits. This condition predominates in males, between 30 and 60 years. In this article, the authors present a case report of a 47-year-old man that resorted to consultation to perform routine medical exams, without any complaint associated. Physical examination shows multiple bilateral swellings in the proximal region of the upper limbs and analytically presents hyperuricemia, hypertriglyceridemia, hypercholesterolemia and changes in hepatic tests. CT revealed the presence of non-encapsulated homogeneous masses of adipose tissue in the proximal region of the limbs. Currently the patient is asymptomatic, being monitoring in consultation.

关键词： Symmetric Multiple Lipomatosis Hyperuricemia Hypertriglyceridemia Hypercholesterolemia

Capsule enteroscopy is useful for the therapeutic management of Crohn's disease

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World Journal of Gastroenterology 2015年第44期21卷 12660-12666页

作者： Joao Santos-Antunes Hélder Cardoso Susana Lopes Margarida Marques Amadeu CR Nunes Guilherme macedo Gastroenterology department Faculty of Medicine Hospital de Sao Joao department of Biochemistry (U38-FCT) Faculty of Medicine University of Porto

AIM: To analyze therapeutic changes in Crohn's disease(CD) patients following video capsule endoscopy(VCE) and to assess the usefulness of Lewis score and the Patency ***: Patency Capsule was performed in every patient that had indication for VCE, and those with negative patency did not undergo VCE. Patients with established CD that underwent VCE between January 2011 and February 2014 were selected for this study; those with suspected CD were excluded, independent of VCE results, since our purpose was to address differences in therapeutic regimen in CD patients before and after VCE. Patients with inconclusive VCE were also excluded. Patients had to be free of non-steroidal anti-inflammatories for at least 1 mo. Those patients who met these criteria were allocated into one of three groups: Staging group(asymptomatic CD patients that underwent VCE for staging of CD), Flare group(patients with active CD), or Post-op group(CD patients evaluated for post-operative recurrence). Lewis score was calculated for every VCE procedure. Statisticalanalysis was performed to address the impact of VCE findings on the therapeutic management of CD patients and to evaluate the utility of the Lewis ***: From a total of 542 VCEs, 135 were performed in patients with CD. Patency capsule excluded nearly 25% of the patients who were supposed to undergo VCE. No videocapsule retention during VCE was reported. From these 135 patients, 29 were excluded because CD diagnosis was not established at the time of VCE. Therefore, a total of 106 patients were included in the final analysis. From these, the majority were in the Staging group(n = 73, 69%), and the remaining were in the Flare(n = 23, 22%) or Post-op(n = 10, 9%) group. Median time between diagnosis and VCE was 5.5 years. Overall, VCE determined changes in the treatment of 40% of patients: only 21% remained free of immunosuppressors after VCE compared to 44% before VCE(P < 0.001). The differences in therapy before and a

关键词： Capsule enteroscopy Crohn's disease Treatment modification Patency capsule Lewis score