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Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

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Science China(Life Sciences) 2024年第5期67卷 1010-1026页

作者： Ziyue Qin Yanxing Han Yifei Du Yixuan Zhang Yifeng Bian Ruyu Wang Haoran Wang Fanyi Guo Hua Yuan Yongchu Pan Jianliang Jin Qigang Zhou Yuli Wang Feng Han Yan Xu Jiandong Jiang Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Province key laboratory of Oral diseases Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing 210029China State key laboratoryof BioactiveSubstances andFunction of Natural Medicine Instituteof Materia MedicaChinese Academyof MedicalSciencesandPeking Union MedicalCollegeBeijing100050China Gusu school Nanjing medical universitySuzhou 215002China key laboratory of Cardiovascular&cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical UniversityNanjing 211166 China Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Human Anatomy Research Centre for Bone and Stem CellsKey Laboratory for Aging&DiseaseThe State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjing 211166China Department of Clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing Jiangsu211166China Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Virology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this ***(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic *** this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone *** from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in *** clarify the underlying mechanism,the bioactive materials were applied to different animal *** discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the *** of pure M-CSF attenuated experimental periodontal alveolar bone loss in ***-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated ***,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or *** results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT *** studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction ***,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

关键词： berberine human bone marrow mesenchymal stem cells alveolar bone regeneration macrophage colony-stimulating factor AKT phosphorylation

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Free-moving-state microscopic imaging of cerebral oxygenation and hemodynamics with a photoacoustic fiberscope

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Light(Science & Applications) 2024年第1期13卷 33-46页

作者： Xiaoxuan Zhong Yizhi Liang Xiaoyu Wang Haoying Lan Xue Bai Long Jin Bai-Ou Guan Guangdong Provincial key laboratory of Optical Fiber Sensing and Communications Institute of Photonics TechnologyJinan UniversityGuangzhou510632China

We report the development of a head-mounted photoacoustic fiberscope for cerebral imaging in a freely behaving *** 4.5-gram imaging probe has a 9-µm lateral resolution and 0.2-Hz frame rate over a 1.2-mm wide *** probe can continuously monitor cerebral oxygenation and hemodynamic responses at single-vessel resolution,showing significantly different cerebrovascular responses to external stimuli under anesthesia and in the freely moving *** example,when subjected to high-concentration CO_(2) respiration,enhanced oxygenation to compensate for hypercapnia can be visualized due to cerebral regulation in the freely moving *** studies exhibit significantly weakened compensation capabilities in obese *** new imaging modality can be used for investigating both normal and pathological cerebrovascular functions and shows great promise for studying cerebral activity,disorders and their treatments.

关键词： cerebral anesthesia moving

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Flexible electrochemical fiber sensor for intracranial nitric oxide monitoring

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Science China Chemistry 2024年第8期67卷 2431-2433页

作者： Ziwei Liu Huisheng Peng State key laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceInstitute of Fiber Materials and Devicesand Laboratory of Advanced MaterialsFudan UniversityShanghai 200438China

Real-time and accurate monitoring of vital biomarkers in vivo forms a crucial foundation for health assessment,early intervention,and disease ***,continuous monitoring of intracranial nitric oxide(NO)levels plays a pivotal role in promptly assessing immune responses,neurovirulence,and cerebrovascular diseases[1].Differing from non-real-time monitoring methods like chemiluminescence[2]and fluorescent probes[3],implantable electrochemical sensors excel in simultaneously high temporal resolution,sensitivity,and cost-effectiveness[4].

关键词： prompt electrochemical monitoring

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Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 66-74页

作者： Xuan Sun Ming Yang Dapeng Sun Guangge Peng Yiming Deng Xingquan Zhao Liping Liu Ning Ma Feng Gao Dapeng Mo Wengui Yu Yongjun Wang Yilong Wang Zhongrong Miao Department of Interventional Neuroradiology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Neurology Comprehensive Stroke&Cerebrovascular CenterUniversity of California IrvineIrvineCaliforniaUSA Chinese Institute for Brain Research BeijingChina National Center for Neurological diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical Research Center for Neurological diseases BeijingChina Beijing laboratory of Oral Health Capital Medical UniversityBeijingChina

Background The superiority of balloon angioplasty plus aggressive medical management(AMM)to AMM alone for symptomatic intracranial artery stenosis(sICAS)on efficacy and safety profiles still lacks evidence from randomised controlled trials(RCTs).Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for *** Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis(BASIS)trial is a multicentre,prospective,randomised,open-label,blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with *** eligible in BASIS were 35–80 years old,with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis(70%–99%)of a major intracranial *** eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 *** groups will receive identical AMM,including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy,intensive risk factor management and life-style *** participants will be followed up for *** outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up,or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment,is the primary *** BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients,which may provide an alternative perspective for treating *** registration number NCT03703635;https://***.

关键词： balloon prospective centre

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Traditional craniotomy versus current minimally invasive surgery for spontaneous supratentorial intracerebral haemorrhage:A propensity-matched analysis

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World Journal of Radiology 2024年第8期16卷 317-328页

作者： Zhen-Kun Xiao Yong-Hong Duan Xin-Yu Mao Ri-Chu Liang Min Zhou Yong-Mei Yang Hengyang key laboratory of Hemorrhagic cerebrovascular Disease Department of NeurosurgeryHengyang Medical SchoolUniversity of South ChinaHengyang 421000Hunan ProvinceChina Department of Anatomy Hengyang Medical SchoolUniversity of South ChinaHengyang 421000Hunan ProvinceChina

BACKGROUND Minimally invasive surgery(MIS)and craniotomy(CI)are the current treatments for spontaneous supratentorial cerebral haemorrhage(SSTICH).AIM To compare the efficacy and safety of MIS and CI for the treatment of *** Clinical and imaging data of 557 consecutive patients with SSTICH who underwent MIS or CI between January 2017 and December 2022 were retrospectively *** patients were divided into two subgroups:The MIS group and CI *** score matching was performed to minimise case selection *** primary outcome was a dichotomous prognostic(favourable or unfavourable)outcome based on the modified Rankin Scale(mRS)score at 3 months;an mRS score of 0–2 was considered *** In both conventional statistical and binary logistic regression analyses,the MIS group had a better *** outcome of propensity score matching was unexpected(odds ratio:0.582;95%CI:0.281–1.204;P=0.144),which indicated that,after excluding the interference of each confounder,different surgical modalities were more effective,and there was no significant difference in their *** Deciding between MIS and CI should be made based on the individual patient,considering the hematoma size,degree of midline shift,cerebral swelling,and preoperative Glasgow Coma Scale score.

关键词： Cerebral haemorrhage Intracerebral haemorrhage Minimally invasive surgery Craniotomy Propensity-matched analysis

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GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun Xu Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu key laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial key Discipline of Neurology Nanjing210008China Nanjing Neurology Medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal *** inflammation is associated with the occurrence and development of ***,the mechanisms underlying the formation of the abnormal vascular network remain ***-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in *** found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and *** summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF

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Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways

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Journal of Biomedical Research 2024年第4期38卷 322-333页

作者： Pengxiang Min Yingying Li Cuirong Wang Junting Fan Shangming Liu Xiang Chen Yamin Tang Feng Han Aixia Zhang Lili Feng key laboratory of Cardiovascular&cerebrovascular Medicine International Joint Laboratory for Drug Target of Critical IllnessesSchool of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China Department of Pharmaceutical Analysis School of PharmacyNanjing Medical UniversityNanjingJiangsu 210029China Department of Analysis and Testing Center School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical UniversityNanjingJiangsu 211166China Department of Clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China

Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical *** mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic *** date,there is still a lack of effective drugs that target VM formation in *** the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular *** significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal *** RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of *** to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM ***,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-***,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated ***,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.

关键词： moroidin vasculogenic mimicry glioblastoma EMT β-catenin

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Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

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Acta Pharmaceutica Sinica B 2024年第1期14卷 1-19页

作者： Weile Ye Jiaojiao Wang Peter JLittle Jiami Zou Zhihua Zheng Jing Lu Yanjun Yin Hao Liu Dongmei Zhang Peiqing Liu Suowen Xu Wencai Ye Zhiping Liu International Cooperative laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China Jinan UniversityGuangzhou 510632China Guangdong Province key laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China State key laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 510632China Pharmacy Australia Centre of Excellence School of PharmacyUniversity of QueenslandWoolloongabba QLD 4102Australia Sunshine Coast Health Institute and School of Health and Behavioural Sciences University of the Sunshine CoastBirtinya QLD 4575Australia National-Local Joint Engineering Lab of Druggability and New Drugs Evaluation Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Bengbu Medical CollegeBengbu 233030China Institute of Endocrine and Metabolic diseases the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of *** biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for *** studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease *** clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia ***,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and *** highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and ***,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

关键词： Cardiovascular disease Atherosclerosis Ginkgo biloba Ginkgolide B Endothelial dysfunction LOX-1 PCSK9 PAF-R antagonist

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Intracerebral haemorrhage: from clinical settings to animal models

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Stroke & Vascular Neurology 2020年第4期5卷 388-395页

作者： Qian Bai Zhaofu Sheng Yang Liu Ruiyi Zhang Voon Wee Yong Mengzhou Xue The Departments of cerebrovascular diseases Henan Medical Key Laboratory of Translational Cerebrovascular DiseasesThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Hotchkiss Brain Institute and Department of Clinical Neurosciences University of CalgaryCalgaryAlbertaCanada

Spontaneous intracerebral haemorrhage(ICH)is a devastating type of stroke with high mortality and morbidity and for which no effective treatments are available to *** experimental and clinical research have been performed to explore its mechanisms regard the subsequent inflammatory cascade and to seek the potential therapeutic *** aim of this review is to discuss insights from clinical settings that have led to the development of numerous animal models of *** of the current and future challenges for clinicians to understand ICH are also surveyed.

关键词： clinical mortality cerebral

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NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease

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Stroke & Vascular Neurology 2023年第2期8卷 161-168页

作者： Yun-chao Wang Yu Fan Wen-Kai Yu Si Shen Jia-Di Li Yuan Gao Yan Ji Yu-Sheng Li Lu-Lu Yu Zi-Chen Zhao Shan-Shan Li Yao Ding Chang-He Shi Yu-ming Xu Department of Neurology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina NHC key laboratory of Prevention and Treatment of cerebrovascular diseases ZhengzhouHenanChina Department of Neurology Xinxiang Medical UniversityXinxiangHenanChina

Objective GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease(NIID).Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease(CSVD),both diseases have white matter hyperintensity on T2-fluid attenuated inversion recovery sequences of brain MRI,and white matter hyperintensity is a primary neuroimaging marker of CSVD on ***,we hypothesised that the GGC repeat expansions might also contribute to *** further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD,we performed a genetic analysis of 814 patients with the *** We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic *** Fazekas score was greater than or equal to 3 ***-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions,and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with *** We identified nine(1.11%)patients with pathogenic GGC repeat expansions ranging from 41 to 98 *** minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%.Conclusion Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic *** provides new thinking for studying the pathogenesis of CSVD.

关键词： patients cerebral expanded

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