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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

EZH2-dependent myelination following sciatic nerve injury

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Neural Regeneration Research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi Huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue Research Center of Clinical medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical School of Nantong University NantongJiangsu ProvinceChina department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina department of Rehabilitation medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina department of critical care medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating Schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination Schwann cells sciatic nerve crush sciatic nerve transection

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

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Neural Regeneration Research 2025年第11期20卷 3302-3316页

作者： Yali Chen Yiyong Wei Jin Liu Tao Zhu Cheng Zhou Donghang Zhang department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Laboratory of Anesthesia and critical care medicine National-Local Joint Engineering Research Center of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan ProvinceChina department of Anesthesiology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)ShenzhenGuangdong ProvinceChina department of Anesthesiology Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative *** cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous *** the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal ***,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal *** explore the conservation and divergence across species,we compared these findings with those from *** the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic *** the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,*** comparative results revealed substantial heterogeneity in all glial cell types between humans and ***,we detected sex differences in gene expression in human spinal cord glial ***,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in *** all microglial subtypes,all differentially expressed genes were located on the sex *** addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in ***,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for explo

关键词： astrocyte glial cell human microglia oligodendrocyte sex differentiation single-nucleus RNA sequencing spatial transcriptomics species variation spinal cord

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina department of Neurology The First Hospital of Tsinghua UniversityBeijingChina department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of critical care medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

Eosinophils in asthma

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Chinese Medical Journal 2004年第5期117卷 792-794页

作者：施焕中 department of Pulmonary and critical care medicine

The contribution of eosinophils to host-defense and inflammatory responses has undergone periodic reevalu-ations. Thirty years ago, eosinophil was considered as a principal effector cell in host-defense against parasi... 详细信息

关键词： IL SCH Eosinophils in asthma

Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B

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World Journal of Gastroenterology 2005年第8期11卷 1109-1114页

作者： Keiichi Fujiwara Osamu Yokosuka Hiroshige Kojima Tatsuo Kanda Hiromitsu Saisho Hiroyuki Hirasawa Hiroshi Suzuki department of medicine and Clinical Oncology department of Emergency and critical care medicine department of Surgery

AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in 'clinically severe' exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with life-threatening severe exacerbation of chronic hepatitis B. METHODS: Twenty-two patients, 14 men and 8 women, were defined as 'severe' exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ('early high-dose' group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ('non-early high-dose' group). RESULTS: Mean age, male-to-female ratio, mean prothrombin time (FT) activity, alanine transaminase (ALT) level, total bilirubin level, positivity of HBeAg, mean IgM-HBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the 'early high-dose' group survived, while only 2 of 11 patients of the 'non-early high-dose' group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the 'early high-dose' group. Both ALT levels and HBV DNA polymerase levels fell in both groups. CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with 'clinically life-threatening' severe exacerbation of chronic hepatitis B , when used in the early stage of illness.

关键词： Chronic hepatitis B Severe exacerbation Immunosuppressive therapy

Strategic insights of telehealth platforms and strengths,weaknesses,opportunities,and threats analysis of Amazon's clinical endeavors

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维普期刊数据库

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World Journal of Methodology 2025年第2期15卷 145-153页

作者： Harpreet Grewal Gagandeep Dhillon Venkata Buddhavarapu Ram Kishun Verma Ripudaman Singh Munjal Pranjal Sharma Gurmanpreet Sidhu Rahul Kashyap Salim Surani department of Radiology Ascension Sacred Heart HospitalPensacolaFL 32503United States department of medicine UM Baltimore Washington Medical CenterGlen BurnieMD 21061United States department of medicine Banner Baywood Medical CenterBanner HealthMesaAZ 85206United States department of Sleep medicine Parkview Health SystemFort WayneIN 46845United States department of medicine Touro university College of Osteopathic MedicineVallejoCA 94592United States department of Nephrology Northeast Ohio Medical CenterRootstownOH 44272United States department of Pathology Government Medical College PatialaPatiala 147001PunjabIndia department of Research Wellspan HealthYorkPA 17403United States Division of Pulmonary and critical care medicine Mayo ClinicRochesterMN 55905United States department of medicine&Pharmacology Texas A&M UniversityCollege StationTX 77843United States

BACKGROUND The adoption of telehealth services surged after the coronavirus disease 2019 pandemic,revolutionizing traditional healthcare delivery *** Clinic's recent nationwide launch marks a significant milestone in this *** study aims to offer a strengths,weaknesses,opportunities,and threats(SWOT)analysis of Amazon Clinic and compare its features with leading virtual healthcare *** To evaluate Amazon Clinic's telehealth services through a SWOT analysis and compare its features with other leading virtual healthcare *** The initial search terms included were,amazon clinic odds ratio(OR)amwell OR Teladoc OR Walmart virtual health service OR CVS minute clinic OR CirrusMD OR brightside health,from 2000 to *** search yielded 111 articles,from which duplicates were removed,and unrelated titles were filtered *** articles were retained for a final review,including comparative studies,usability research,retrospective analyses,observational studies,and review *** data was organized and analyzed using Rayyan software and summarized in a table and PRISMA *** The review included eight articles focusing on various aspects of *** studies highlighted differences between Teladoc and traditional physician offices,noting lower diagnostic imaging orders and antibiotic prescriptions for *** demographics for Teladoc showed younger,less engaged *** studies emphasized the importance of website design for telemedicine ***-mental health platforms like Brightside showed superior outcomes in treating depression compared to traditional *** for specialized fields like skin reconstruction demonstrated cost efficiency and reduced waiting *** SWOT analysis identified Amazon Clinic's strengths,such as its vast consumer base and transparent pricing,and weaknesses like the lack of pediatric *** included potential partnerships and servi

关键词： Tele-health Amazon COVID-19 Primary care Outpatient clinic SWOT Telemedicine

Intraoperative glycemic control procedures and the use of an artificial pancreas

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World Journal of Gastroenterology 2009年第33期15卷 4126-4131页

作者： Koichi Yamashita Tomoaki Yatabe department of Anesthesiology and critical care medicine Kochi Medical School

Strict intraoperative glycemic control can significantly decrease the incidence of postoperative infection; however, anesthesiologists must carefully control blood glucose levels as well as properly manage the respiratory and cardiovascular systems. However, standard blood glucose measurement systems and insulin dosing algorithms, which are necessary for achieving strict glycemic control, have not yet been developed. An artificial pancreas (STG-22TM; Nikkiso Co., Tokyo, Japan) is considered a highly accurate blood glucose monitoring system capable of closed-loop control of blood glucose. The device has, however, many problems to be addressed since it is a large and expensive system with little versatility, and it requires a large amount of blood to be collected. Therefore, the development of less invasive and inexpensive systems with future technological progress is greatly anticipated.

关键词： Strict glycemic control Artificial pancreas Anesthesiologist Sliding scale

Obesity paradox in patients with community-acquired pneumonia:Have you fully considered the confounding factors?

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World Journal of Clinical Cases 2025年第9期13卷 53-55页

作者： Jin-Ke Sun Hui Tian department of Pulmonary and critical care medicine Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250000Shandong ProvinceChina department of critical care medicine Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina

There exists a notion that there is an obesity paradox in the prognosis of community-acquired *** other words,obese individuals with communityacquired pneumonia have a better *** study by Wang et al supports this claim,but we believe that the obesity paradox should not be proposed hastily as it is influenced by numerous subjective and objective confounding factors.

关键词： Community-acquired pneumonia Mortality Body mass index Overweight Obesity paradox