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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.kobeis.y 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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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily firas.kobeis.y Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel Jonathan Grossberg Daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

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Neural Regeneration Research 2025年第4期20卷 1079-1080页

作者： Victor V.Chizhikov Igor y.Iskusnykh Department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in *** cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

关键词： epithelium Figure center

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The optimal semi-analytical modeling for the infinite-conductivity horizontal well performance under rectangular bounded reservoir based on a new instantaneous source function

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Petroleum 2024年第1期10卷 68-84页

作者： firas A.A.Al-Kabbawi Independent scholar LivingstonScotlandUNITED KINGDOM

The main objective of this study is to develop the optimal semi-analytical modeling for the infiniteconductivity horizontal well performance under rectangular bounded reservoir based on a new instantaneous source *** available semi-analytical infinite-conductivity models(ICMs)for horizontal well under rectangular bounded reservoir in literature were developed by applying superposition of pressures in space(SPS).A new instantaneous source function(i.e.,instantaneous uniform-flux segmentary source function under bounded reservoir)is derived to be used instead of SPS to develop the optimal semi-analytical *** new semi-analytical ICM is verified with ICM of Schlumberger[1]and with previous semi-analytical ICMs in terms of bottom hole pressure(BHP)profile and inflow rate distribution along the *** model is also validated with real horizontal wells in terms of inflow rate distribution along the *** results show that the developed model gives the optimal semi-analytical modeling for the infinite-conductivity horizontal well performance under rectangular bounded *** that,high computationalefficiency and high-resolution of wellbore discretization have been achieved(i.e.,wellbore segment number could be tens of hundreds depending on solution requirement).The results also show that at pseudosteady state(PSS)flow regime,inflow rate distribution along the wellbore by previous semi-analytical ICMs is stabilized U-shaped as performance of inflow rate distribution at late radial flow ***,the previous semi-analytical ICMs are incorrectly modeling inflow rate distribution at PSS flow regime due to the negative influence of applying *** optimal semi-analytical ICM is in a general form and real time domain,and can be applicable for 3D horizontal well and 2D vertical fracture well under infinite and rectangular bounded reservoirs,of uniform-flux and infinite-conductivity wellbore conditions at any time of well life.

关键词： Infinite-conductivity model Horizontal well performance Semi-analytical modeling Rectangular bounded reservoir Instantaneous source functions Flow regimes

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Overview, prevention and management of chemotherapy extravasation

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World Journal of Clinical Oncology 2016年第1期7卷 87-97页

作者： firas y Kreidieh Hiba A Moukadem Nagi S El Saghir Division of Hematology-Oncology Department of Internal Medicine American University of Beirut Medical Center Breast Center of Excellence NK Basile Cancer Institute American University of Beirut Medical Center

Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, pre-vention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.

关键词： Chemotherapy Extravasation Vesicant Tissue damage Dimethyl sulfoxide Dexrazoxane Antidote Hyaluronidase

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S y yau Kwok-Fai So Li Zhang Haining Ou Department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Using the image processing in digital system to determine the nuclear parameters of LR-115 detector

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Radiation Detection Technology and Methods 2021年第2期5卷 255-263页

作者： firas Mohammed Ali Al‑jomaily Physics Department Science CollegeMosul UniversityMosulIraq

Background The relative resolution of the nuclear track detector to distinguish between the different energies of alpha particles has been *** This done by modeling the nuclear track of LR-115 detector,the revealed tracks have been classified and their diameters were measured with numerical densities replication depending on the fitting by resonance Breit–Wigner formula,the optimum etching time was chose with the least standard deviation of the spectral distribution of tracks diameter according to the average track diameter(D).Purpose The spectral distribution width(ΔD)was determined at Full Width at Half Maxima(FWHM).The results and comparisons showed the resonance Breit–Wigner formula it had a preference in improving the relative resolution of the detector as compared with the Gaussian and Wblfit *** turns out the application of image analysis software by MATLAB technique leads to give fast and accurate nuclear track parameters for *** The digitally counting system is high accurate and infinite speed in completing the *** results obtained with respect to the measurement of 238U concentration in the standard samples,showed the superiority of digitally system in the determination of these concentration in comparison with manually system,with average error rate no exceeding of 4.175%.

关键词： LR-115 SSNT’D Digitally system Relative resolution Image processing

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第2期9卷 154-159页

作者： firas A. AL-BAyATI Hassan F. AL-MOLA Department of Biology College of Education University of Mosul Mosul-00964 Iraq

Antimicrobial activity of organic and aqueous extracts from fruits, leaves and roots of Tribulus terrestris L., an Iraqi medicinal plant used as urinary anti-infective in folk medicine, was examined against I l species of pathogenic and non-pathogenic microorganisms： Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Corynebacterium diphtheriae, Escherichia coli, Proteus vulgaris, Serratia marcescens, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans using microdilution method in 96 multiwell microtiter plates. All the extracts from the different parts of the plant showed antimicrobial activity against most tested microorganisms. The most active extract against both Gram-negative and Gram-positive bacteria was ethanol extract from the fruits with a minimal inhibitory concentration （MIC） value of 0.15 mg/ml against B. subtilis, B. cereus, P. vulgaris and C. diphtheriae. In addition, the same extract from the same plant part demonstrated the strongest antifungal activity against C. albicans with an MIC value of 0.15 mg/ml.

关键词： Antimicrobial activity Tribulus terrestris Urinary tract infections

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Experimental Study of Heat Transfer Enhancement in Solar Tower Receiver Using Internal Fins

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Computers, Materials & Continua 2021年第8期68卷 1693-1711页

作者： Hashem Shatnawi Chin Wai Lim firas Basim Ismail Abdulrahman Aldossary Education Sector in Jubail Jubail Technical InstituteJubail Industrial City31961Saudi Arabia Mechanical Engineering Department College of EngineeringUniversiti Tenaga NasionalKajang43000SelangorMalaysia Power Generation Unit Institute of Power Engineering(IPE)Universiti Tenaga NasionalKajang43000SelangorMalaysia

The receiver is an important element in solar energy *** principal receiver’s tubes in power plants are devised to work under extremely severe conditions,including excessive heat *** of the tube’s circumference is heated whilst the other half is *** study aims to improve the heat transfer process and reinforce the tubes’structure by designing a new receiver;by including longitudinal fins of triangular,circular and square *** research is conducted experimentally using Reynolds numbers ranging from 28,000 to 78,*** fins have demonstrated the best improvement for heat *** Reynolds number value near 43,000 Nusselt number(Nu)is higher by 3.5%and 7.5%,sequentially,compared to circular and square tube fins,but varies up to 6.5%near Re=*** lowest friction factor is seen in a triangular fin receiver;where it deviates from circular fins by 4.6%,and square fin tubes by 3.2%.Adding fins makes the temperature decrease gradually,and in the case of no fins,the temperature gradient between the hot tube and water drops sharply in the planed tube by 7%.

关键词： Solar tower power external receiver longitudinal internal fins thermocouples temperature gradient

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