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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang department of Neurology Henry Ford HospitalDetroitMIUSA department of Physics Oakland UniversityRochesterMIUSA department of pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu department of pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

Helicobacter pylori infection in subjects negative for high titer serum antibody

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World Journal of Gastroenterology 2018年第13期24卷 1419-1428页

作者： Osamu Toyoshima Toshihiro Nishizawa Masahide Arita Yosuke Kataoka Kosuke Sakitani Shuntaro Yoshida Hiroharu Yamashita Keisuke Hata Hidenobu Watanabe Hidekazu Suzuki department of Gastroenterology Toyoshima Endoscopy Clinic department of pathology Pathology and Cytology Laboratory Japan Medical Education Center Keio University School of Medicine

AIM To investigate the clinicopathological features of the patients testing negative for high titer serum antiHelicobacter pylori(H. pylori) *** The antibody titers were measured using antigens derived from Japanese individuals. ^(13)C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and *** Of the 136 subjects enrolled, 23(17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve(0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10^(-20)) for predicting H. pylori infection with a cutoff value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies(89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate *** Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients.

关键词： Kyoto classification Gastritis Helicobacter pylori Antibody Endoscopy

Pan-TRK positive uterine sarcoma in immunohistochemistry without neurotrophic tyrosine receptor kinase gene fusions:A case report

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World Journal of Clinical Cases 2025年第2期13卷 39-49页

作者： Seungmee Lee Yu-Ra Jeon Changmin Shin Sun-Young Kwon Sojin Shin department of Obstetrics and Gynecology Keimyung University School of MedicineDaegu 42601South Korea department of pathology and Institute for Cancer Research Keimyung University School of MedicineDaegu 42601South Korea

BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic *** on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent ***-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion *** SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic *** examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK ***,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage *** The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive *** such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.

关键词： Uterine sarcoma Cervical sarcoma Neurotrophic tyrosine receptor kinase gene fusion Next generation sequencing Case report

Oxidative stress: the lowest common denominator of multiple diseases

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Neural Regeneration Research 2019年第2期14卷 238-241页

作者： Veronika Matschke Carsten Theiss Johann Matschke Institute of anatomy Department of Cytology Ruhr University Bochum Institute of Cell Biology (Cancer Research) University of Duisburg-Essen University Hospital Essen

Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis. When the concentration of free radicals exceeds a critical level and homeostasis is disturbed, oxidative stress occurs leading to damage of multiple cellular molecules and compartments. Therefore, oxidative stress plays an important role in the physiology and pathology of various diseases. Often, the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases, leading to functional losses of the organism, as in the case of amyotrophic lateral sclerosis, or cells develop metabolic mechanisms to use this system as protection against external influences, such as in the case of glioblastoma cells. Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases. Thus, regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate, the focus should be on the oxidative protection system.

关键词： neurodegenerative disease amyotrophic lateral sclerosis cancer glioblastoma reactive oxygen species metabolism antioxidant protection system

Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

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World Journal of Stem Cells 2016年第4期8卷 136-157页

作者： Donnahue Dennie Jean-Pierre Louboutin David S Strayer Section of anatomy Department of Basic Medical SciencesUniversity of the West IndiesMona Campus department of Cell Biology Anatomy and PathologyThomas Jefferson University

Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory *** molecular markers can be used to characterizethe cells involved in adult *** has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal *** explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced ***-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)*** of transgene-expressing cells expressed NeuN,a marker of mature ***,BM-derived cells may function as progenitors of CNS cells in adult *** mechanism by which the cells from the BM come to be neurons remains to be *** the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled *** studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature ***-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the *** addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal *** cells were actively proliferating,as shown by short term BrdU incorporation *** seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors migrating

关键词： Stem cells Bone marrow Hippocampus Cell therapy SV40 Brain Nestin Doublecortin Neurons Development Epilepsy Seizures

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA department of pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Aberrant DNA repair as a potential contributor for the clonal evolution in subsets of anaplastic thyroid carcinomas arising through dedifferentiation: implications for future therapeutic algorithms?

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Cancer Drug Resistance 2020年第4期3卷 992-1000页

作者： Carl Christofer Juhlin department of Oncology-pathology Karolinska InstitutetStockholm SE-17176Sweden department of pathology and cytology Karolinska University HospitalStockholm SE-17176Sweden

Well-differentiated thyroid carcinoma(WDTC,including papillary thyroid carcinoma and follicular thyroid carcinoma)are fairly slow-growing tumors with an overall low mortality due to the efficacy of combinatory surgery and postoperative radioiodine *** of WDTCs may dedifferentiate into poorly differentiated thyroid carcinoma(PDTC)and anaplastic thyroid carcinoma(ATC),of which especially the latter has an exceptionally poor patient *** underlying genetics responsible for this tumor progression is only partly understood,and is complicated by the fact that subgroups of ATCs are thought to arise de novo without a demonstrable,pre-existing *** so,recent advances using next generation sequencing(NGS)techniques have identified a genetic link between WDTCs and ATCs,suggesting a step-wise accumulation of mutations driving the loss of differentiation for most *** this Commentary,recent findings from an NGS study on synchronous FTC,PDTC,and ATC tumor components from the same patient are *** using whole-genome data,clonality analyses identified a chief ancestral clone carrying mutations in TP53-associated signaling networks regulating genes involved in DNA repair,with sub-clones in each tumor component that were identified also in the less differentiated,neighboring ***,mutational signatures suggested a general mismatch repair(MMR)deficiency along with microsatellite *** findings support the chained progression model of dedifferentiation in thyroid cancer,and pinpoint a central role for defective DNA *** effective treatment modalities for ATCs are urgently needed,studies regarding therapeutic agents specifically targeting defective MMR in dedifferentiated thyroid carcinoma could be pursued.

关键词： DNA repair mismatch repair P53 thyroid carcinoma dedifferentiation anaplastic thyroid carcinoma clone treatment

An unusual mixed germ cell tumor of the testis consisting of rhabdomyosarcoma, mature teratoma and yolk sac tumor

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Asian Journal of Andrology 2010年第3期12卷 451-452页

作者： Eva Lovric Dubravka Bobonj Hizak Melita Peric Balja Tanja Lenicek Bozo Kruslin department of pathology and cytology Cakovec County Hospital Cakovec 40000 Croatia department of pathology Bjelovar General Hospital Bjelovar 43000 Croatia department of pathology University Hospital for Tumors Zagreb 10000 Croatia Ljudevit Jurak University department of pathology Sestre milosrdnice University Hospital Zagreb 10000 Croatia

Dear Editor, We recently encountered a rare case of testicular mixed germ cell tumor （MGCT） in a 32-year-old man. The tumor was composed of a combination of a yolk sac tumor, teratoma and rhabdomyosarcomatous somat... 详细信息

关键词： unusual testis consisting rhabdomyosarcoma