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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Exosomes as mediators of neuron-glia communication in neuroinflammation

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Neural Regeneration Research 2020年第5期15卷 796-801页

作者： María Pascual Francesc Ibánez Consuelo Guerri Department of Molecular and Cellular Pathology of Alcohol Príncipe Felipe Research CenterValenciaSpain Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain

In recent years,a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological *** nanovesicles (30–150 nm) contain proteins,RNAs and lipids,and their internalization by bystander cells could alter their normal *** review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous *** emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain,in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative *** the small size and characteristics of exosomes,they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and ***,although the application potential of exosome is still limited,current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation.

关键词： biomarkers exosomes glial cells neuroinflammation neuron-glia commuication neurons neuropathology therapy

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Radioiodine labeled SP-4 as an imaging agent foratherosclerotic plaques

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Nuclear Science and Techniques 2000年第4期11卷 234-239页

作者： ZHANG Yong-Xue, WU Zhi-Jian, CAO Wei (Union Hospital, Huazhong University of Science and Technology, Wuhan 430022) 华中科技大学湖北武汉 430022

The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labeled with 131I and 125I by the Chloramine--T method and purified through Sephadex G25 column. Tewlve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR ). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then fed with high cholesterol and fat diet. 125I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125I-SP-4 in rabbits was investigated. The uptakes (%ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macroautoradiography and microautoradiography were performed in 2 AR atheroscle-rotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4hours postinjection were significantly higher than that of NR. The films of macroautoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of microautoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent.

关键词：放射性碘标记 SP-4 临床应用放射性显像药物诊断动脉粥样硬化实验兔动物实验

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Glycemic index of cereals and tubers produced in China

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World Journal of Gastroenterology 2006年第21期12卷 3430-3433页

作者： Yue-Xin Yang Hong-Wei Wang Hong-Mei Cui Yan Wang Lian-Da Yu Shi-Xue Xiang Shui-Ying Zhou Institute of Nutrition and Food Safety Chinese Center for Disease Control and Prevention Beijing 100050 China Department of Endocrinology the First Hospital of Chaoyang Liaoning Province China Center for Disease Control and Prevention of Ningxia Autonomous Regio n Yinehuan 750004 Ningxia Hui Minority Autonomous Region China Sichuan Center for Disease Control and Prevention Chengdu 610031 Sichuan Province China Huangshi Institute of health Inspection Huangshi 435000 Hubei Province China

AIM： To determine the GI of some cereals and tubers produced in China in an effort to establish the database of glycemic index （GI） of Chinese ***： Food containing 50 g carbohydrate was consumed by 8-12 healthy adults after they have been fasted for 10 h and blood glucose was monitored for 2 h. Glucose was used as reference food. GI of food was calculated according to a standard ***： GI of 9 types of sugar and 60 kinds of food were ***： Food GI is mainly determined by nature of carbohydrate and procession. Most of cereals and tubers produced in China have similar GI with their counterparts produced in other countries.

关键词： Glycemic Index Cereals Tubers Carbohydrate

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Clonal expansion shapes the human Vδ1T cell receptor repertoire

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Cellular & Molecular Immunology 2018年第2期15卷 96-98页

作者： Serena Meraviglia Francesco Dieli Central Laboratory of Advanced Diagnosis and Biomedical Research(CLADIBIOR)and Department of Biopathology and Medical Biotechnologies(DIBIMED) University of PalermoPalermo90129Italy

Theγδcells are a unique population of T lymphocytes that combine innate-like features and adaptive-type responses and play an important role in the early host response to infections and *** fromαβT cells,γδT cells recognize a limited set of antigens,which are shared by a variety of microbial pathogens and tumor cells in a non-MHC restricted manner;1 thus,these cells use the TCR in a manner similar to a pattern recognition receptor(PRR).Moreover,whereasαβT cells require antigen-and cytokine-driven clonal expansion,γδT cells are equipped with immediate effector functions.1 However,the potentialγδrepertoire with junctional diversity is estimated at∼10^(18),which is much greater than theαβrepertoire(∼10^(16)),thus raising questions concerning the forces governing the selection of such a huge TCR repertoire during ontogeny and whether and how theγδTCR repertoire is shaped under physiological and pathological conditions.

关键词： expansion equipped concerning

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Influence of comorbidity on outcomes of older patients with acute pancreatitis based on a national administrative database

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Hepatobiliary & Pancreatic Diseases International 2015年第4期14卷 422-428页

作者： Atsuhiko Murata Makoto Ohtani Keiji Muramatsu Shinya Matsuda Department of Preventive Medicine and Community health School of Medicine University of Occupational and Environmental Health

Little information is available on the influ- ence of comorbidities on outcomes of older patients with acute pancreatitis. This study aimed to investigate the influence of co- morbidities on outcomes of older patients with acute pancreati- tis using data from a national Iapanese administrative database. METHODS： A total of 14 322 older patients （〉70 years） with acute pancreatitis were referred to 1090 hospitals between 2010 and 2012 in Japan. We collected patients＇ data from the administrative database to compare the in-hospital mortal- ity and length of stay of older patients with acute pancreatitis. The patients were categorized into four groups according to comorbidity level using the Charlson Comorbidity Index （CCI）： none （CCI score=0; n=6890）; mild （1; n=3874）; moder- ate （2; n=2192） and severe （〉3; n=1366）. RESULTS： Multiple logistic and linear regression analyses revealed that severe comorbidity was significantly associated with higher in-hospital mortality and longer length of stay [odds ratio （OR）=2.26; 95% confidence interval （CI）： 1.75-2.92, P〈0.001 and coefficient 4.37 days; 95% CI： 2.89-5.85, P〈0.001, respectively]. In addition, cardiovascular and renal diseases were the most significant comorbidities affecting outcomes of the older patients. ORs of cardiovascular and renal diseases for mortality were 1.44 （95% CI： 1.13-1.85, P=0.003） and 2.69 （95% CI： 1.88-3.85, P〈0.001）, respectively, and coefficients forlength of stay were 3.01 days （95% CI： 1.34-4.67, P〈0.001） and 3.72 days （95% CI： 1.01-6.42, P=0.007）, respectively. CONCLUSION： This study demonstrated that comorbidities significantly influenced outcomes of older patients with acute pancreatitis and cardiovascular and renal comorbidities were significant factors affecting outcomes.

关键词： acute pancreatitis comorbidity length of stay databases

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Expression of mutant type-p53 products in H pylori-associated chronic gastritis

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World Journal of Gastroenterology 2007年第10期13卷 1541-1546页

作者： Masaaki Kodama Kazunari Murakami Tadayoshi Okimoto Ryugo Sato Koichiro Watanabe Toshio Fujioka Department of Gastroenterology Faculty of MedicineOita UniversityHasama-machiOita879-5593Japan

AIM： To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and aEer H pylori eradication therapy. METHODS： 53 subjects （36 male, 17 female, mean age ± SEM, 57.1 ± 12.1） undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylorinegative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 （DO-7 and PAb240）. RESULTS： p53 （DO-7 and PAb240） immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 （PAb240）in the Hpylori-infected gastric mucosa. The proportion of patients immunopositive for p53 （PAb240） was significantly reduced 6 mo after eradication [28/42 （66.7%） to 6/42 （14.3%）] （P 〈 0.05）, while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 （PAb240）. p53 （PAb240）-positive patients were divided into two groups by the number of positive cells detected： one with more than six positive cells per 10 gastric pits （group A, n = 12）, and the other with less than five positive cells per 10 gastric pits （group B, n = 30）. Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum （group A： 2.00 ± 0.14 vs group B： 1.40 ± 0.15, P = 0.012）, the lesser curvature of the corpus （group A： 2.00 ± 0.21 vs group B： 1.07 ± 0.23, P = 0.017）, and the greater curvature of the corpus （group A： 1.20 ± 0.30 vs group B： 0.47 ±0.21, P = 0.031）. Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum （group A： 2.10 ± 0.41 vs group B： 1.12 ± 0.29, P = 0.035）. CONCLUSION： H pylori-associated chronic gastritis expressed the mutant-type p53, w

关键词： H pylori H pylori eradication Atrophic gastritis Mutant-type p53 Gastric cancer Updated Sydney system

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A mouse model for HBV immunotolerance and immunotherapy

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Cellular & Molecular Immunology 2014年第1期11卷 71-78页

作者： Dan Yang Longchao Liu Danming Zhu Hua Peng Lishan Su Yang-Xin Fu Liguo Zhang BP-UC Group for Immunotherapy CAS Key Laboratory for Infection and Immunity Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill NC USA Department of Pathology the University of Chicago 924E 57 Street Chicago IL60637

Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus （HBV） infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus （AAV） carrying a replicable HBV genome （AAV/ HBV）. Similar to the clinical HBV carriers, the mice infected with AAV/H BV were sero-negative for antibodies against HBV surface antigen （HBsAg）. Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/H BV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism（s） of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections.

关键词： AAV vector HBV immunotherapy immunotolerance mouse model

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