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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)

Regulation of sleep by astrocytes in the hypothalamic ventrolateral preoptic nucleus

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Neural Regeneration Research 2025年第4期20卷 1098-1100页

作者： Jae-Hong Kim Ruqayya Afridi Il-Sung Jang Maan Gee Lee Kyoungho Suk Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of Pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of Pharmacology School of DentistryKyungpook National UniversityDaeguRepublic of Korea Brain Science&Engineering Institute Kyungpook National UniversityDaeguRepublic of Korea

Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s *** astrocytic regulation of neuronal activity has been increasingly recognized in recent *** are now recognized as playing a more complex role than mere bystanders in the central nervous ***,their role in regulating the sleep neurocircuitry is not well *** this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the *** briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.

关键词： sleep ventrolateral astrocytes

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

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University school of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

A review on recent taxonomic updates of gut bacteria associated with social bees,with a curated genomic reference database

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Insect Science 2025年第1期32卷 2-23页

作者： Chengfeng Yang Jiawei Hu Qinzhi Su Zijing Zhang Yating Du Jieni Wang Huihui Sun Benfeng Han Junbo Tang Lizhen Guo Hu Li Wanzhi Cai Hao Zheng Xin Zhou Xue Zhang Department of Entomology College of Plant ProtectionChina Agricultural UniversityBeijingChina Sanya Institute of China Agricultural University Hainan ProvinceChina College of Food Science and Nutritional Engineering China Agricultural UniversityBeijingChina Beijing Laboratory of Biomedical Materials Department of Geriatric DentistryPeking University School and Hospital of StomatologyBeijingChina Hebei Key Laboratory of Animal Physiology Biochemistry and Molecular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuangChina

Honeybees and bumblebees play a crucial role as essential *** special gut microbiome of social bees is a key factor in determining the overall fitness and health of the *** bees harbor relatively simple microbial communities at the genus level,recent studies have unveiled significant genetic divergence and variations in gene content within each bacterial ***,a comprehensive and refined genomics-based taxonomic database specific to social bee gut microbiomes remains ***,we first provided an overview of the current knowledge on the distribution and function of social bee gut bacteria,as well as the factors that influence the gut population *** then consolidated all available genomes of the gut bacteria of social bees and refined the species-level taxonomy,by constructing a maximum-likelihood core genome phylogeny and calculating genome-wide pairwise average nucleotide *** the basis of the refined species taxonomy,we constructed a curated genomic reference database,named the bee gut microbe genome sequence database(BGM-GDb).To evaluate the species-profiling performance of the curated BGM-GDb,we retrieved a series of bee gut metagenomic data and inferred the species-level composition using metagenomic intra-species diversity analysis system(MIDAS),and then compared the results with those obtained from a prebuilt MIDAS *** found that compared with the default database,the BGM-GDb excelled in aligned read counts and bacterial ***,this high-resolution and precise genomic reference database will facilitate research in understanding the gut community structure of social bees.

关键词： bacterial species BGM-GDb corbiculate bees gut microbiome phylogeny phylotype

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome:Focusing on inflammation and molecular mechanisms

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Animal Models and Experimental Medicine 2025年第1期8卷 5-19页

作者： Mohammad Yasin Zamanian Hamidreza Zafari Maria K.Osminina Alla A.Skakodub Raed Fanoukh Aboqader Al-Aouadi Maryam Golmohammadi Nikta Nikbakht Iman Fatemi Department of Physiology School of MedicineHamadan University of Medical SciencesHamadanIran Department of Pharmacology and Toxicology School of PharmacyHamadan University of Medical SciencesHamadanIran Department of Orthopedic Surgery Joint Reconstruction Research CenterImam Khomeini Hospital ComplexSchool of MedicineTehran University of Medical SciencesTehranIran Pediatric department I.M.Sechenov First Moscow State Medical University of the Ministry of Health of Russia(Sechenov University)MoscowRussian Federation Department of Pediatric Preventive dentistry E.V.Borovsky I.M.Sechenov First Moscow State Medical University of the Ministry of Health of Russia(Sechenov University)MoscowRussian Federation Department of Medicine College of MedicineAl-Ayen Iraqi UniversityThi-QarIraq school of Medicine Shahid Beheshti University of Medical SciencesTehranIran Department of Physical Medicine and Rehabilitation School of PharmacyHamadan University of Medical SciencesHamadanIran Research Center of Tropical and Infectious Diseases Kerman University of Medical SciencesKermanIran

Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global *** therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse ***(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive *** delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing *** study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of *** from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free *** liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher *** anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of ***,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory *** findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

关键词： dexamethasone inflammation liposome rheumatoid arthritis TNF-α

Changes in factor profiles deriving from photochemical losses of volatile organic compounds:Insight from daytime and nighttime positive matrix factorization ana

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Journal of Environmental Sciences 2025年第5期151卷 627-639页

作者： Baoshuang Liu Tao Yang Sicong Kang Fuquan Wang Haixu Zhang Man Xu Wei Wang Jinrui Bai Shaojie Song Qili Dai Yinchang Feng Philip K.Hopke State Environmental Protection Key Laboratory of Urban Ambient Air Particulate Matter Pollution Prevention and Control&Tianjin Key Laboratory of Urban Transport Emission Research College of Environmental Science and EngineeringNankai UniversityTianjin 300350China CMA-NKU Cooperative Laboratory for Atmospheric Environment-Health Research Tianjin 300350China Beijing Make Environment Science&Technology Co. Ltd.Beijing 100083China Shijiazhuang Environmental Prediction Center Shijiazhuang 050022China Department of Public Health Sciences University of Rochester School of Medicine and DentistryRochesterNY 14642USA Institute for a Sustainable Environment Clarkson UniversityPotsdamNY 13699USA

Substantial effects of photochemical reaction losses of volatile organic compounds(VOCs)on factor profiles can be investigated by comparing the differences between daytime and nighttime dispersion-normalized VOC data resolved *** speciated VOC data measured in Shijiazhuang,China from May to September 2021 were used to conduct *** mean VOC concentration in the daytime and at nighttime were 32.8 and 36.0 ppbv,*** and aromatics concentrations in the daytime(12.9 and 3.08 ppbv)were lower than nighttime(15.5 and 3.63 ppbv),whereas that of alkenes showed the opposite *** concentration differences between daytime and nighttime for alkynes and halogenated hydrocarbonswere uniformly *** reactivities of the dominant species in factor profiles for gasoline emissions,natural gas and diesel vehicles,and liquefied petroleum gas were relatively low and their profiles were less affected by photochemical *** losses produced a substantial impact on the profiles of solvent use,petrochemical industry emissions,combustion sources,and biogenic emissions where the dominant species in these factor profiles had high *** the profile of biogenic emissions was substantially affected by photochemical loss of isoprene,the low emissions at nighttime also had an important impact on its *** losses of highly active VOC species substantially reduced their concentrations in apportioned factor *** study results were consistent with the analytical results obtained through initial concentration estimation,suggesting that the initial concentration estimation could be the most effective currently availablemethod for the source analyses of active VOCs although with uncertainty.

关键词： Volatile organic compounds Dispersion normalization Photochemical loss Factor profile Positive matrix factorization

Chemical characteristics and sources apportionment of volatile organic compounds in the primary urban area of Shijiazhuang,North China Plain

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Journal of Environmental Sciences 2025年第3期149卷 465-475页

作者： Xiao Zhang Junfeng Wang Jiangwei Zhao Junliang He Yali Lei Kai Meng RuiWei Xue Zhang Miaomiao Zhang Shuangying Ni Eleonora Aruffo College of geographical sciences and Environment Shijiazhuang UniversityShijiazhuang 050035China Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control Collaborative Innovation Center of Atmospheric Environment and Equipment TechnologySchool of Environmental Science and EngineeringNanjing University of Information Science and TechnologyNanjing 210044China Hebei Province Ecology Environmental Monitoring Center Shijiazhuang 050037China Key Lab of Geographic Information Science of the Ministry of Education School of Geographic SciencesEast China Normal UniversityShanghai 200241China Hebei Provincial Institute of Meteorological Sciences Shijiazhuang 050021China Key Laboratory of Meteorology and Ecological Environment of Hebei Province Shijiazhuang 050021China Hebei Provincial Academy of Ecological Environmental Science Shijiazhuang 050037China Department of Advanced Technologies in Medicine&dentistry University“G.d’Annunzio”of Chieti-PescaraChieti 66100Italy Center for Advanced Studies and Technology-CAST Chieti 66100Italy

VOCs(Volatile organic compounds)exert a vital role in ozone and secondary organic aerosol production,necessitating investigations into their concentration,chemical characteristics,and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric *** to October 2020,onlinemonitoringwas conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and ***,the PMF(positive matrix factorization)method was utilized to identify the VOCs *** indicated that the TVOCs(total VOCs)concentration was(96.7±63.4μg/m^3),with alkanes exhibiting the highest concentration of(36.1±26.4μg/m^3),followed by OVOCs(16.4±14.4μg/m^3).The key active components were alkenes and aromatics,among which xylene,propylene,toluene,propionaldehyde,acetaldehyde,ethylene,and styrene played crucial roles as reactive *** sources derived from PMF analysis encompassed vehicle emissions,solvent and coating sources,combustion sources,industrial emissions sources,as well as plant sources,the contribution of which were 37.80%,27.93%,16.57%,15.24%,and 2.46%,***,reducing vehicular exhaust emissions and encouraging neighboring industries to adopt low-volatile organic solvents and coatings should be prioritized to mitigate VOCs levels.

关键词： Volatile organic compounds Pollution characteristics Ozone formation potential OH radical loss rate Source apportionment

Dopaminergic effects on in vitro osteogenesis

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Bone Research 2015年第3期3卷 130-139页

作者： Dong Joon Lee Henry C Tseng Sing Wai Wong Zhengyan Wang Meng Deng Ching-Chang Ko NC Oral Health Institute School of Dentistry University of North Carolina Duke Eye Center and Department of Ophthalmology Duke University Medical Center Oral Biology Program School of Dentistry University of North Carolina Department of Pediatric dentistry School of Dentistry University of North Carolina Department of Orthodontics School of Dentistry University of North Carolina

Multiple growth factors（e.g., BMP2, TGF-b1, FGF2） and isolated genes have been shown to improve osteoblastic proliferation and mineralization, advancing bone tissue engineering. Among these factors, both polydopamine（PDA） and dopamine（DA） monomer have recently been reported to increase osteoblast proliferation and mineralization in vitro. Although a well-characterized neurotransmitter, DA＇s role in the bone is unknown. We hypothesize that DA can directly act on osteoblasts, and examined whether osteoblasts express DA receptors that respond to exogenous DA. m RNAs and protein cell lysates were obtained from MC3T3-E1 cells during osteogenic differentiation phase. Reverse transcription polymerase chain reaction and western blot analysis were used to examine the expression of DA receptors, D1–D5. Dose-response effect and time course of DA treatment on cell proliferation, mineralization, and osteogenic differentiation were investigated at pre-determined days. Real-time PCR was performed to investigate whether DA affects osteogenic gene expression（ALP, BSP, OC, OSX, RUNX2, and Collagen1a2） with or without receptor antagonists（SCH233390 and GR103691）. Two-way ANOVA was used for statistical analysis. All five DA receptors（D1, D2, D3, D4, and D5） m RNAs and proteins were expressed in MC3T3-E1 cells. DA treatment increased cell proliferation for up to 7 days（P, 0.05）. Osteogenic mineralization was significantly greater in the DA-treated group than control group（P, 0.05）. Finally, expression of all the osteogenic genes was inhibited by DA receptor antagonists for D1, D3, and D5. Our findings suggest that MC3T3-E1 osteoblasts express functional DA receptors that enhance proliferation and mineralization. PDA is not biologically inert and has important implications in orthopedic applications. Furthermore, osteoblast differentiation might be regulated by the nervous system, presumably during bone development, remodeling, or repair.

关键词： osteogenic differentiation cell proliferation polymerase chain reaction bone tissue engineering western blot analysis statistical analysis bone development gene expression nervous system growth factors in vitro