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Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3730-3745页

作者： Qinxiang Zheng Chaoxiang Ge Kexin Li Longxin Wang Xiaoyu Xia Xiao Liu Rashid Mehmood Jianliang Shen Kaihui Nan Wei Chen Sen Lin National Engineering Research Center of Ophthalmology and Optometry Eye HospitalWenzhou Medical UniversityWenzhou 325027China National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027China Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China School of Chemical Engineering UNSW SydneyHigh StreetBuilding E10KensingtonNSW 2052Australia adult cancer program Lowy Cancer Research CentreUNSW SydneyCorner Botany&High StreetsKensingtonNSW 2052Australia

Dexamethasone(DEX)is used to treat ocular surface ***,regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side *** this study,a novel magnetic nanoparticle(MNP)-micelle(MC)codelivery system(MMDS)was *** MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive *** extend its residency,the MMDS was magnetically attracted by an external magnet after instilling,which acted as a precorneal drug-depot enabling a sustainable release of DEX in *** combination of magnet treatment,the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva,as well as concurrently reduced the DEX-level in the aqueous humor,when compared with the commercial DEX eye drop *** combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension,commercial DEX eye drops,as well as the MMDS@DEX treatment *** present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects,which will be beneficial to the treatments of a wide range of ocular surface diseases.

关键词： Magnetic nanoparticle Micelle Dexamethasone Eye drop Bioavailability Dry eye disease Cornea Conjunctiva

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Betalains protect various body organs through antioxidant and anti-inflammatory pathways

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Food Science and Human Wellness 2024年第3期13卷 1109-1117页

作者： Nilesh Prakash Nirmal Seema Medhe Merina Dahal Pankaj Koirala Siriwan Nirmal Fahad Al-Asmari Baojun Xu Institute of Nutrition Mahidol UniversityNakhon Pathom 73170Thailand Department of Nutrition and Dietetics Central Campus of TechnologyTribhuvan UniversityKathmandu 46000Nepal Department of adult Nursing Faculty of NursingBurapha UniversityChonburi 20131Thailand Department of Food Science and Nutrition College of Agriculture and Food SciencesKing Faisal UniversityAl-Ahsa 31982Saudi Arabia Food Science and Technology program Department of Life SciencesBNU-HKBU United International CollegeZhuhai 519088China

Betalains are natural coloring pigments with betalamic acid as the core structure of all *** their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly *** in-vivo studies reported that betalains protect various body organs,leading to health *** organs,including the heart,liver,kidney,lung,etc.,are important for a healthy ***,these organs can be affected or damaged by various stress factors,toxicants,and harmful *** studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory *** review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ***,future research directions and conclusions have been outlined.

关键词： Betalains Antioxidant Anti-inflammatory Bioactivities Ogans-protection

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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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The dual role of striatal interneurons:circuit modulation and trophic support for the basal ganglia

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Neural Regeneration Research 2024年第6期19卷 1277-1283页

作者： Elliot Wegman Marlena Wosiski-Kuhn Yu Luo Department of Molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Department of Emergency Medicine at the School of Medicine University of CincinnatiCincinnatiOHUSA Neuroscience Graduate program University of CincinnatiCincinnatiOHUSA

Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional *** not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson's or Huntington's *** review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease *** addition to direct circuit modulation,striatal interneurons have also been shown to provide trophic support to maintain neuron populations in *** discuss this interesting and novel role of striatal interneurons,with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog.

关键词： cholinergic dopamine GABAergic interneuron levodopa-induced dyskinesia parvalbumin sonic hedgehog striatum trophic factor

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Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma

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Engineered Regeneration 2024年第2期5卷 199-209页

作者： Feng Liang Xueying An Ruoxi Wang Wenshu Wu Lin Yang Yixin Zheng Qing Jiang Xingquan Xu Danni Zhong Min Zhou Eye Center The Second Affiliated HospitalZhejiang University School of MedicineHangzhou310000PR China Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhou310000PR China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008PR China Zhejiang University-University of Edinburgh Institute(ZJU-UoE Institute) Zhejiang University School of MedicineZhejiang UniversityHaining314400PR China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalClinical College of Nanjing Medical UniversityNanjing210008PR China Institute of Translational Medicine Zhejiang UniversityHangzhou310029PR China Zhejiang University-Ordos City Etuoke Banner Joint Research Center Zhejiang UniversityHaining314400PR China

Osteosarcoma(OS)is one of the most common malignant tumors in children and young *** chemotherapy and other therapies are limited by low therapeutic efficiency,severe side effects and single therapeutic function,it is of high value to develop innovative therapies for precise and efficient treatment of ***,natural photo-synthetic microalgae(***,CV)were utilized as carriers for the chemotherapeutic agent doxorubicin(DOX)to create a multifunctional therapeutic platform(CV@DOX)for the photo-modulation of the tumor microenvi-ronment(TME)and synergistic chemo-photodynamic therapy of ***@DOX exhibited rapid drug release behavior in the acidic TME,improving the efficiency of chemotherapy against tumors and reducing side effects on other normal *** 650 nm laser irradiation,CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species(ROS),thereby enhancing photodynamic therapy(PDT).CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis,inhibiting tumor proliferation and ***,chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after ***,CV@DOX did not cause significant hematological and tissue toxicity,and prevented DOX-induced cardiotoxicity,showing good in vivo ***,this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosar-coma treatment.

关键词： Osteosarcoma Tumor hypoxia Photodynamic Chemotherapy Synergistic therapy

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Constructing osteo-inductive bio-ink for 3D printing through hybridization of gelatin with maleic acid modified bacterial cellulose by regulating addition volumes of maleic acid solution

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Journal of Bioresources and Bioproducts 2024年第3期9卷 336-350页

作者： Xucai Wang Dengxian Wu Wei Liao Yaxuan Liu Wenhui Pei Jixian Wang Jiayu Gu Peng Wang Kai Lan Caoxing Huang Co-Innovation Center for Efficient Processing and Utilization of Forest Resources College of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China State Key Laboratory of Pharmaceutical Biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNahanjing 210008China Children's Hospital of Nanjing Medical University Nanjing 210008China Jiangsu Institute of Metrology Nanjing 210023China Department of Forest Biomaterials College of Natural ResourcesNorth Carolina State UniversityRaleigh NC 27695USA

Bacterial cellulose(BC)is an exopolysaccharide with unique properties that has been applied in various ***,the dense and intertwined nature of BC fibers limits its use in certain applications,including 3D printing scaffolds for bone *** this work,a controllable BC-based bio-ink for 3D printing was successfully prepared by modifying the neat BC through maleic acid(MA)treatment,aiming to promote bone tissue *** achieve homogeneous BC dispersions while preserving its crystalline and chemical properties,BC was modified by MA solution(60%,w/V)with solid-liquid ratio from 1꞉5 to 1꞉50(w/V)to obtain MA-BC *** analysis results from microstructure,chemical group,crystallinity,and wettability indicated that the BC/MA solution with ratio of 1꞉30 demonstrated the best pre-treatment performance to obtain ***,by combining MA-BC with gelatin,we successfully formulated MA-BC-GEL gels with favorable rheological properties and compression modulus,which can be used as promising bio-inks for 3D bioprinting *** vitro tests demonstrated 1꞉30 MA-BC possessed excellent biocompatibility,a significant ability to express the alkaline phosphatase gene and osteogenic-related genes,and facilitated the formation of mineralized *** utilization of this novel bio-ink in scaffold preparation for bone regeneration highlights the promising application of modified BC in bone tissue engineering field.

关键词： Bacterial cellulose Maleic acid Osteogenic activity Printability

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Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren Ping Liu Shanghai Institute of Hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International Center for Aging and cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

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Enhancing osteogenic bioactivities of coaxial electrospinning nanoscaffolds through incorporating iron oxide nanoparticles and icaritin for bone regeneration

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Nano Research 2024年第7期17卷 6430-6442页

作者： Peng Wang Qianjin Wang Dengxian Wu Yunyang Zhang Shixiong Kang Xucai Wang Jiayu Gu Hao Wu Zhihong Xu Qing Jiang School of Biomedical Engineering and Informatics Nanjing Medical UniversityNanjing 211166China State Key Laboratory of Pharmaceutical Biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Center of Modem Analysis Nanjing UniversityNanjing 210008China State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210009China Co-Innovation Center for Efficient Processing and Utilization of Forest Resources College of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China Jiangsu Institute of Metrology Nanjing 210023China

Bone tissue engineering provides a promising strategy for the treatment of bone ***,the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive ***,we proposed to endow nano-scaffold(NS)constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles(IONPs)and icaritin(ICA).Four types of nano-scaffolds(NS,ICA@NS,NS-IONPs and ICA@NS-IONPs)were *** incorporation of ICA and IONPs minimally impact their surface morphological and chemical *** enhanced the mechanical properties of NS scaffolds,including hardness,tensile strength,and elastic *** vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase(ALP)activity level,expressions of osteogenesis-related genes and proteins as well as mineralized nodule *** investigations revealed that MEK/ERK(MAP kinase-ERK kinase(MEK)/extracellularsignal-regulated kinase(ERK))signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@***,the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone ***,IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.

关键词： iron oxide nanoparticles icaritin coaxial electrospinning nano-scaffolds MEK/ERK signaling pathway bone regeneration

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Characterization of genetically engineered mouse models carrying Col2a1-cre-induced deletions of Lrp5 and/or Lrp6

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Bone Research 2015年第4期3卷 235-245页

作者： Cassie A Schumacher Danese M Joiner Kennen D Less Melissa Oosterhouse Drewry Bart O Williams Center for cancer and Cell Biology Program in Skeletal Disease and Tumor MicroenvironmentVan Andel Research Institute

Mice carrying Collagen2a1-cre-mediated deletions of Lrp5 and/or Lrp6 were created and *** lacking either gene alone were viable and fertile with normal knee *** in which both Lrp5 and Lrp6 were conditionally ablated via Collagen2al-cre-mediated deletion displayed severe defects in skeletal development during *** addition,adult mice carrying Collagen2al-cre-mediated deletions of Lrp5 and/or Lrp6 displayed low bone mass suggesting that the Collagen2a1-cre transgene was active in cells that subsequently differentiated into *** both embryonic skeletal development and establishment of adult bone mass,Lrp5 and Lrp6 carry out redundant functions.

关键词： carrying Collagen displayed deletion engineered transgene viable embryogenesis redundant embryonic

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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