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Intranasal administration of stem cell-derived exosomes for central nervous system diseases

Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho Gotoh Masahito Kawabori Miki Fujimura department of Neurosurgery Hokkaido University Graduate School of Medicine

Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including antiapoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

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Z-shaped incision without epithelial resection in pterygium surgery

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1262-1266页

作者： Satoru Kase Shinki Chin Susumu Ishida department of Ophthalmology Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

AIM:To introduce a novel surgical technique using a Z-shaped incision without epithelial resection in ophthalmic ***:This was a prospective *** pterygium surgery,all proliferative tissues were separated from the cornea and conjunctiva without resection of the *** unaffected conjunctiva was incised in a *** upper(or lower)conjunctival flap was sutured to the lower(or upper)normal conjunctiva on the limbal sclera,while the proliferative tissue was sutured to the upper conjunctiva(or lower)near the ***:Ten patients with pterygia were eligible for this *** patients with primary pterygia and 2 with recurrent pterygia were *** age of patients at surgery ranged from 47 to 90y(average:71.9y).Five patients each showed right and left-sided *** postoperative follow-up periods were from 8 to 78mo(average:25.0mo).The surgery was successfully conducted and wounds were favorably reconstructed in all *** proliferative tissues sutured to the normal conjunctiva showed palor and attenuated neovessles,and never showed re-growth after *** patients did not show *** pterygium was noted in 1 patient,but additional treatments were not ***:The procedure involves the reconstruction of pterygial tissue and normal conjunctiva using a Z-shaped *** scleral limbal wound can be covered with nonaffected conjunctiva without any excision of conjunctival epithelia in patients with primary or recurrent pterygia.

关键词： pterygium surgery Z-shape non-resection

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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 Cincinnati 2. Department of Emergency Medicine at the School of Medicine University of Cincinnati Neuroscience graduate Program University of Cincinnati

Striatal interneurons play a key role in modulating striatal-dependent behaviors, including motor activity and reward and emotional processing. Interneurons 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 disease. This 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 conditions. In addition to direct circuit modulation, striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood. We 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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Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

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Neural Regeneration Research 2024年第9期19卷 1954-1960页

作者： Kinya Matsuo Hideaki Nshihara Yamaguchi University graduate school of medicine YamaguchiJapan department of Neurotherapeutics Yamaguchi UniversityUbeJapan

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous ***-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s ***,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal ***,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective *** elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional ***,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been *** in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain *** this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell ***,we discuss the potential future directions for blood-brain barrier research.

关键词： Alzheimer’s disease blood-brain barrier human induced pluripotent stem cells

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Effect of Guanxin Danshen Dripping Pills on Coronary Heart Disease Comorbid with Depression or Anxiety: The ADECODE-Real World Study

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Chinese Journal of Integrative medicine 2024年第5期30卷 443-448页

作者： WU Shi-hao SHI Wei-qi LI Yu-hang LIU Ru-hui HU Da-yi ZHENG Li-qiang MA Wen-lin department of geriatric medicine Tongji HospitalSchool of MedicineTongji UniversityShanghai 200065China department of Cardiology Tongji HospitalSchool of MedicineTongji UniversityShanghai 200065China department of Cardiology Peking University People's HospitalBeijing 100044China school of Public Health Shanghai Jiao Tong UniversityShanghai 200030China

Objective: To evaluate the efficacy of Guanxin Danshen Dripping Pill(GXDSDP) in treating anxiety and depression in patients with coronary heart disease(CHD). Methods: A total of 1,428 patients diagnosed with CHD screened for anxiety, depression, and quality of life(QOL) at baseline received 0.4 g of GXDSDP treatment 3 times per day and returned for monthly reassessment. Patients were recruited after stable treatment for CHD and received assessment of General Anxiety Disorder-7(GAD-7), Patient Health Questionnaire-9(PHQ-9), and Seattle Angina Questionnaire(SAQ) for evaluating anxiety, depression, and *** were followed up 3 times, once every 4 weeks, during outpatient visits for 12 weeks. Results: At the third follow-up(F3), the anxiety symptom of 63.79%(673/1,055) of the patients improved to sub-clinical level, and the GAD-7 score improved significantly(8.11 vs. 3.87, P<0.01);57.52%(585/1,017) patients' depressive symptoms improved to sub-clinical level, with a significant improvement in PHQ-9 score(8.69 vs. 4.41, P<0.01) at F3. All aspects of QOL significantly improved at the end of treatment compared to those at baseline(all P<0.01) as assessed by SAQ: physical limitation(31.17 vs. 34.14), anginal stability(2.74 vs. 4.14), anginal frequency(8.16vs. 9.10), treatment satisfaction(13.43 vs. 16.29), and disease perception(8.69 vs. 11.02). Conclusions: A fixed dosage of GXDSDP may be a potential treatment option for CHD patients comorbid with anxiety or depression.(Registration No. ChiCTR2100051523)

关键词： Guanxin Danshen Dripping Pill coronary heart disease depression anxiety quality of life Chinese medicine

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Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 135-149页

作者： Rui Wang Tongyao Liu Xinhong Li Enhao Lu Yiting Chen Kuankuan Luo Tao Wang Xueli Huang Zhiwen Zhang Shilin Du Xianyi Sha Key Laboratory of Smart Drug Delivery Ministry of Education Institutes of Integrative MedicineDepartment of PharmaceuticsSchool of PharmacyFudan University department of Emergency medicine Shanghai Geriatric Medical Center department of Emergency medicine Zhongshan HospitalFudan University

Flare and multiple recurrences pose significant challenges in gouty *** treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent *** should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis,calling for therapeutic systems to achieve these two goals *** this study,we propose a biomimetic integrated nanozyme,HMPB-Pt@MM,comprising platinum nanozyme and hollow Prussian *** demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory ***,it rapidly targets inflamed ankles through the camouflage of macrophage ***,HMPB-Pt@MM exhibits urate oxidase-like capabilities,continuously metabolizing locally elevated uric acid concentrations,ultimately inhibiting multiple recurrences of gouty *** summary,HMPB-Pt@MM integrates ROS clearance with uric acid metabolism,offering a promising platform for the treatment of gouty arthritis.

关键词： Gouty arthritis Inflammation Nanozyme Platinum Prussian blue

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^(18)F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer:A systematic review and meta-analysis

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Chinese Medical Journal 2024年第8期137卷 949-958页

作者： Zhengtong Lv Liuqi Song Miao Wang Huimin Hou Haodong Li Xuan Wang Jianye Wang Jianlong Wang Ming Liu department of Urology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China graduate school of Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100730China Peking University Fifth school of Clinical medicine Beijing 100730China Peking University China-Japan Friendship school of Clinical medicine Beijing 100029China

Background:Lymph node staging of prostate cancer(PCa)is important for planning and monitoring of treatment.^(18)F-prostate specific membrane antigen positron emission tomography/computerized tomography(^(18)F-PSMA PET/CT)has several advantages over^(68)Ga-PSMA PET/CT,but its diagnostic value requires further *** meta-analysis focused on establishing the diagnostic utility of^(18)F-PSMA PET/CT for lymph node staging in medium/high-risk ***:We searched the EMBASE,PubMed,Cochrane library,and Web of Science databases from inception to October 1,*** cancer,^(18)F,lymph node,PSMA,and PET/CT were used as search terms and the language was limited to *** additionally performed a manual search using the reference lists of key *** and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included ***,specificity,the positive and negative likelihood ratio(PLR and NLR),diagnostic odds ratio(DOR),area under the curve(AUC),and 95%confidence interval(CI)were used to evaluate the diagnostic value of^(18)F-PSMA PET/*** 17 software was employed for calculation and statistical ***:A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this *** the patient level,the results of each consolidated summary were as follows:sensitivity of 0.57(95%CI 0.39-0.73),specificity of 0.95(95%CI 0.92-0.97),PLR of 11.2(95%CI 6.6-19.0),NLR of 0.46(95%CI 0.31-0.68),DOR of 25(95%CI 11-54),and AUC of 0.94(95%CI 0.92-0.96).At the lesion level,the results of each consolidated summary were as follows:sensitivity of 0.40(95%CI 0.21-0.62),specificity of 0.99(95%CI 0.95-1.00),PLR of 40.0(95%CI 9.1-176.3),NLR of 0.61(95%CI 0.42-0.87),DOR of 66(95%CI 14-311),and AUC of 0.86(95%CI 0.83-0.89).Conclusions:^(18)F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk *** diag

关键词： ^(18)F-PSMA PET/CT Diagnostic test Lymph node Meta-analysis Prostate cancer

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Epigenetic memory of drug exposure history controls neural stem cell quiescence in the adult brain

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Neural Regeneration Research 2024年第4期19卷 711-712页

作者： Masakazu Iwamoto Taito Matsuda department of Stem Cell Biology and medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous *** adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.

关键词： neural integrate continuously

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Neural plasticity in Parkinson's disease: a neuroimaging perspective

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Neural Regeneration Research 2024年第6期19卷 1203-1205页

作者： Christina Andica Koji Kamagata department of Radiology Juntendo University Graduate School of Medicine Faculty of Health Data Science Juntendo University

Parkinson’s disease(PD) is a progressive neurodegenerative disorder characterized primarily by classical motor signs of bradykinesia,rigidity,tremors,and postural instability usually manifesti ng unilate rally or at least *** disease involves a loss of dopaminergic neurons projecting from the substantia nigra pars compacta to the dorsal striatum,

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea department of Immunology and Molecular medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:Immunology and Microbiology graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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