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Engineered nanoparticles for precise targeted drug delivery and enhanced therapeutic efficacy in cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3432-3456页

作者： Xueqiang Peng Jianjun Fang Chuyuan Lou Liang Yang Shaobo Shan Zixian Wang Yutong Chen Hangyu Li Xuexin Li Department of General Surgery The Fourth Affiliated HospitalChina Medical UniversityShenyang 110032China Department of Ophthalmology Xi’an People’s Hospital(Xi’an Fourth Hospital)Xi’an 710004China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 10050China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhou 510060China Department of Pathology Medical CollegeJinan UniversityGuangzhou 510632China Department of Physiology and Pharmacology Karolinska InstitutetStockholm SE-17177Sweden

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune ***,the challenge of practical and precise targeting of malignant cells *** address this,engineered nanoparticles(NPs)have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions,owing to their small size,low immunogenicity,and ease of surface *** comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy,encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic ***,it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic ***,the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy,which could shape the path for future advancements in this promising field.

关键词： Engineered nanoparticles Cancer immunotherapy Drug delivery Bloodebrain barrier Tumor-barrier Nanomedicine Nanomaterial Cancer

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Tumor angiogenesis and anti-angiogenic therapy

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中华医学杂志(英文版) 2024年第17期137卷 2024 Jul 25页

作者： Guo Ziheng Jing Xu Sun Xiaoting Sun Shishuo Yang Yunlong Cao Yihai Department of Pancreatic Surgery West China Hospital Sichuan University Chengdu Sichuan China Department of Microbiology Tumor and Cell Biology Karolinska Institute Stockholm Sweden Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vison and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang China Cancer institute the First Clinical Medical College Xuzhou Medical University Xuzhou Jiangsu China Department of Cellular and Genetic Medicine School of Basic Medical Sciences Fudan University Shanghai China

Anti-angiogenic drugs (AADs), which mainly target the vascular endothelial growth factor-A signaling pathway, have become a therapeutic option for cancer patients for two decades. During this period, tremendous clinical experience of anti-angiogenic therapy has been acquired, new AADs have been developed, and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy. However, improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required. This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development. We revisit the history of concept initiation and AAD discovery, and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

关键词： Angiogenesis Cancer Angiogenesis inhibitors Angiogenic factors Vascular endothelial growth factors Cancer therapy Combined modality therapy

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Angiogenesis in diseases:A half-century excursion from the initial therapeutic concept to current clinical benefits

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Chinese Medical Journal 2024年第6期137卷 636-637页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm 17177Sweden

Except a few tissues such as the cornea and cartilage that are avascular,blood vessels constitute a significant proportion of tissue masses in virtually all *** physiological conditions,the adult vasculature remains quiescent to retain tissue and organ homeostatic *** few or too many blood vessels are associated with the onset and progression of many *** response to injuries,most tissues undergo repair by switching on angiogenesis,a key process of new blood vessel formation.^([1])Similarly,angiogenesis is often active in pathological tissues,including tumors and ischemic tissues to aggravate disease progression.

关键词： injuries organs diseases

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Future options of anti-angiogenic cancer therapy

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Chinese Journal of Cancer 2016年第2期35卷 88-96页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska Institute Department of Medical and Health Sciences Linkoping University Department of Cardiovascular Sciences University of Leicester and NIHR Leicester Cardiovascular Biomedical Research UnitGlenfield Hospital

In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer *** rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer ***,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human *** this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.

关键词： Angiogenesis, Cancer therapy, Anti-angiogenesis, Vascular endothelial growth factor, Biomarker

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Dementia studies in Chinese populations

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Neuroscience Bulletin 2014年第2期30卷 207-216页

作者： Jin-Jing Pei Maria Stella T. Giron Jianping Jia Hui-Xin Wang Department of Neurology Xuan Wu Hospital Capital Medical University Beijing 100053 China KI-Alzheimer's Disease Research Center Department of Neurobiology Care Sciences and Society Karolinska InstitutetNovum 141 86 Stockholm Sweden Aging Research Center Department of Neurobiology Care Sciences and Society Karolinska Institutet and StockholmUniversity G~vlegatan 16 113 30 Stockholm Sweden

Variations in the prevalence of dementia in different ethnic groups have been reported worldwide, and a number of reviews have provided a picture of epidemiological studies in dementia research. However, little is known about epidemiological studies in Chinese populations. In this review, we searched PubMed and the Web of Science for original research articles published in English up to July 2013 on the prevalence, incidence, risk factors, and prognosis of dementia in Chinese populations worldwide. Except for the prevalence, we included only population-based follow-up studies. We identified 25 studies in elderly Chinese residents in China's Mainland, Hong Kong, Taiwan, and Singapore, and found a higher prevalence of dementia in China's Mainland than in the other locations, which may be due to that the studies from China's Mainland are more recent than those from other locations. A notable increase in incidence was observed when dementia cases were diagnosed using 10/66 diagnostic criteria compared to other criteria. Studies on risk factors for dementia were limited and mostly from China's Mainland. Age, gender, education, smoking, and alcohol consumption were related to the risk of dementia in Chinese populations. Only two prognostic studies were identified, and age, gender, and residential area were related to the prognosis of dementia. In conclusion, the prevalence, incidence, and risk factors for dementia found in Chinese populations were comparable to other ethnic groups, but no conclusive results on prognosis were found. The differences in prevalence and incidence were influenced by the diagnostic criteria and the time of study. Longitudinal population-based studies on the incidence, risk factors, and prognosis of dementia in Chinese populations are required.

关键词： dementia epidemiology risk factors prognosis prevalence incidence

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Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

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Translational Neurodegeneration 2023年第1期12卷 801-823页

作者： Luis Enrique Arroyo-García Sara Bachiller Rocío Ruiz Antonio Boza-Serrano Antonio Rodríguez-Moreno Tomas Deierborg Yuniesky Andrade-Talavera AndréFisahn Neuronal Oscillations Laboratory Division of NeurogeriatricsCenter for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164 SolnaSweden Experimental Neuroinflammation Laboratory Department of Experimental Medical ScienceLund UniversityBMC B1122184 LundSweden Clinical Unit of Infectious Diseases Microbiology and ParasitologyInstitute of Biomedicine of Seville(IBiS)Virgen del Rocío University HospitalCSICUniversity of SevilleSevilleSpain Department of Biochemistry and Molecular Biology University of SevilleCalle Profesor García González Nº241012 SevilleSpain Laboratory of Cellular Neuroscience and Plasticity Department of PhysiologyAnatomy and Cellular BiologyUniversidad Pablo de OlavideCarretera de Utrera Km-141013 SevilleSpain Department of Biosciences and Nutrition NeoKarolinska Institutet14183 HuddingeSweden

Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment *** is central to the pathology progression,with evidence suggesting that microglia-released galectin-3(gal3)plays a pivotal role by amplifying neuroinflammation in ***,the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains *** Here,we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo(20-80 Hz)by performing electrophysiological recordings in the hippocampal CA3 area of wild-type(WT)mice and of the 5×FAD mouse model of *** addition,the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes,and amyloid-β(Aβ)plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout(KO).Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner,which was accompanied by impairment of cellular dynamics in fast-spiking interneurons(FSNs)and pyramidal *** found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139,which also prevented Aβ42-induced degradation of gamma ***-more,the 5×FAD mice lacking gal3(5×FAD-Gal3KO)exhibited WT-like gamma network dynamics and decreased Aβplaque *** We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs,inducing a network performance ***,our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.

关键词： Galectin-3 Gamma oscillations Neuronal network dynamics Fast-spiking interneurons Alzheimer’s disease models Neuroinflammation TD139 Hippocampus

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Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease

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Translational Neurodegeneration 2023年第1期12卷 315-328页

作者： Wojciech Paslawski Shervin Khosousi Ellen Hertz Ioanna Markaki Adam Boxer Per Svenningsson Laboratory of Translational Neuropharmacology Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden Memory and Aging Center University of CaliforniaSan FranciscoSan FranciscoCAUSA Basic and Clinical Neuroscience Institute of PsychiatryPsychology and Neurosci-enceKing’s College LondonLondonUK Old Age Psychiatry Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK.

Background There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease(PD).Cerebrospinal fluid(CSF)has been a successful biofluid for finding neurodegenerative biomarkers,and modern highly sensitive multiplexing methods offer the possibility to perform discovery *** a large-scale multiplex proximity extension assay(PEA)approach,we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders(APD).Methods CSF from patients with PD,corticobasal syndrome(CBS),progressive supranuclear palsy(PSP),multiple system atrophy and controls,were analysed with Olink PEA *** cohorts were used in this study,comprising 192,88 and 36 cases,*** samples were run on the Cardiovascular II,Oncology II and Metabolism PEA *** Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts,respectively,compared to *** them,6 proteins were changed in both ***(MK)was increased in PD with the strongest effect size and results were validated with *** most increased protein in PD,DOPA decarboxylase(DDC),which catalyses the decarboxylation of DOPA(L-3,4-dihydroxyphenylalanine)to dopamine,was strongly correlated with dopaminergic ***,Kallikrein 10 was specifically changed in APD compared with both PD and controls,but unchanged between PD and *** inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent *** Using the large-scale PEA approach,we have identified potential novel PD diagnostic biomarkers,most notably MK and DDC,in the CSF of PD patients.

关键词： Atypical Parkinsonian disorders Biomarker Cerebrospinal fluid Corticobasal syndrome DOPA decarboxylase Midkine Multiple system atrophy Parkinson’s disease Progressive supranuclear palsy Proximity extension assay

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Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions:Findings from Global Burden of Disease Study

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Chinese Journal of Cancer Research 2021年第1期33卷 11-26页

作者： Tongchao Zhang Hui Chen Xiaolin Yin Qiufeng He Jinyu Man Xiaorong Yang Ming Lu Department of Epidemiology and Health Statistics School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China Clinical Epidemiology Unit Qilu Hospital of Shandong UniversityJinan 250012China Clinical Research Center of Shandong University Jinan 250012China

Objective:China is one of the countries with the heaviest burden of gastric cancer(GC)in the *** the epidemiological trends and patterns of GC in China can contribute to formulating effective prevention ***:The data on incidence,mortality,and disability-adjusted life-years(DALYs)of GC in China from1990 to 2019 were obtained from the Global Burden of Disease Study(2019).The estimated annual percentage change(EAPC)was calculated to evaluate the temporal trends of disease burden of GC,and the package Nordpred in the R program was used to perform an age-period-cohort analysis to predict the numbers and rates of incidence and mortality in the next 25 ***:The number of incident cases of GC increased from 317.34 thousand in 1990 to 612.82 thousand in2019,while the age-standardized incidence rate(ASIR)of GC decreased from 37.56 per 100,000 in 1990 to 30.64 per 100,000 in 2019,with an EAPC of-0.41[95%confidence interval(95%CI):-0.77,-0.06].Pronounced temporal trends in mortality and DALYs of GC were *** the next 25 years,the numbers of new GC cases and deaths are expected to increase to 738.79 thousand and 454.80 thousand,respectively,while the rates of incidence and deaths should steadily *** deaths and DALYs attributable to smoking were different for males and ***:In China,despite the fact that the rates of GC have decreased during the past three decades,the numbers of new GC cases and deaths increased,and will continue to increase in the next 25 *** strategies are needed to reduce the burden of GC,such as screening and early detection,novel treatments,and the prevention of risk factors.

关键词： Gastric cancer disease burden temporal trend risk factor prediction

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Are you suffering from a large arterial occlusion?Please raise your arm!

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Stroke & Vascular Neurology 2018年第4期3卷 215-221页

作者： Charith Cooray Michael V Mazya Matteo Bottai Jan F Scheitz Azmil H Abdul-Rahim Tiago Prazeres Moreira Robert Mikulik Antonin Krajina Miroslava Nevsimalova Danilo Toni Nils Wahlgren Niaz Ahmed Department of Clinical Neurosciences Karolinska InstitutetStockholmSweden Department of Neurology Karolinska University HospitalStockholmSweden Unit of Biostatistics Institute of Environmental MedicineKarolinska InstitutetStockholmSweden Center for Stroke Research Berlin and Department of Neurology Charité-Universitätsmedizin BerlinBerlinGermany Stroke Research Institute of Cardiovascular and Medical SciencesUniversity of GlasgowGlasgowUK International Clinical Research Center and Neurology Department St.Anne's University Hospital in Brno and Masaryk UniversityBrnoCzech Republic Department of Radiology University HospitalHradec KraloveCzech Republic Comprehensive Cerebrovascular Center HospitalČeskéBudějoviceCeske BudejoviceCzech Republic Emergency Department Stroke Unit Department of Neurology and PsychiatryHospital Policlinico Umberto I'Sapienza'UniversityRomeItaly

Background and purpose Triage tools to identify candidates for thrombectomy are of utmost importance in acute *** prognostic tool has yet gained any widespread *** compared the predictive value of various models based on National institutes of Health Stroke Scale(NIHSS)subitems,ranging from simple to more complex models,for predicting large artery occlusion(LAO)in anterior circulation *** Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were *** compared 2042 patients harbouring an LAO with 2881 patients having no/distal *** binary logistic regression,we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems *** and specificities of the models for predicting LAO were *** The model with highest predictive value included all NIHSS subitems for predicting LAO(area under the curve(AUC)0.77),yielding a sensitivity and specificity of 69%and 76%,*** second most predictive model(AUC 0.76)included 4-NIHSS-subitems(level of consciousness commands,gaze,facial and arm motor function)yielding a sensitivity and specificity of 67%and 75%,*** simplest model included only deficits in arm motor-function(AUC 0.72)for predicting LAO,yielding a sensitivity and specificity of 67%and 72%,*** Although increasingly more complex models yield a higher discriminative performance for predicting LAO,differences between models are not *** grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status,thereby assisting in triage decisions.

关键词： occlusion specificity diagnosis

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Treatment of acute pulmonary edema by blocking VEGF-induced vascular leakage

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Emergency and Critical Care Medicine 2021年第1期1卷 2-5页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden

Pulmonary edema induces local and systemic hypoxia in lungs and other tissues and organs,entailing the development of acute respiratory distress syndrome(ARDS).Hypoxia triggers a myriad of pathological responses,including angiogenesis and hyperpermeability of blood vessels in the lung and other *** endothelial growth factor,also named vascular permeability factor(VPF),is one of the key hypoxia-targeted *** is probably the most potent VPF in the *** this article,I will discuss the possibilities and mechanistic insights of blocking the VEGF signaling pathway for treating acute pulmonary *** particular,anti-VEGF drugs for treating Covid-19-induced pulmonary edema will be discussed.

关键词： Acute respiratory distress syndrome Anti-VEGF therapy Hypoxia Pulmonary edema Vascular endothelial growth factor

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