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Chiral effect on Aβ fibrillation from molecular-scale to nanoscale

Nano Research 2022年第7期15卷 6721-6729页

作者： Guanbin Gao Guowei Zhu Liangchong Yu Zijun Zhang Ting Zhang Xinglin Liu Cheng Zhang Lin Zhou Taolei Sun State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China School of Chemistry Chemical Engineering and Life ScienceWuhan University of TechnologyWuhan 430070China

β-Amyloid(Aβ)peptide fibrillation,one of the characteristic hallmarks of Alzheimer’s disease,is determined by many interfacial physical-chemical factors,e.g.,charge,hydrophobicity,*** extensive research,chiral effect in different-scales on the fibrillation process of Aβremains ***,molecular-scale,sub-nanoscale,and nanoscale chiral-structures were constructed to investigate their chiral effect on the fibrillation of Aβ_(40) *** structures from molecular-scale to nanoscale were obtained from the different periods of the chemosynthesis process of chiral ZnS quantum-dots(QDs),confirmed by real-time monitoring of circular dichroism *** molecular-scale,both L-penicillamine(L-P)and D-P ligands accelerated the fibrillation of Aβ_(40),and the speed-up effect of D-P was slightly stronger than *** sub-nanoscale,both two chiral Zncomplexes(L-Zn and D-Zn)induced the agglomeration of Aβ_(40) without chirality *** nanoscale,both L-ZnS and DZnS QDs inhibited the fibrillation of Aβ_(40),and the inhibition effect of L-ZnS was notably better than that of ***-situ kinetics experiments of Aβ_(40) co-incubated with two chiral QDs demonstrated that L-ZnS completely prevents the misfolding of Aβ_(40) from unfolded toβ-sheet,while D-ZnS cannot achieve *** site-replacement experiments and simulation results revealed the underlying molecular mechanisms of the different inhibition efficiency of chiral ZnS QDs on Aβ_(40) fibrillation,which mainly attribute to the stereoselectivity interaction between the chiral ligands of ZnS QDs and electro-positive amino acid residues(R5,K16,and K28)of Aβ_(40).This work offers a microscopic insight of chiral effect on Aβfibrillation exerted by structures in different-scales,and provides a guidance in precise regulation of protein fibrillation via manipulating chiral structures in different-scales.

关键词： chirality molecular-scale sub-nanoscale nanoscale Aβ_(40) fibrillation

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Curved carbon photo-oxygenation catalysts for the suppression and nanoscopic imaging ofβ-amyloid peptides fibrillation

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Nano Research 2022年第4期15卷 3387-3397页

作者： Yuanyuan Ma Zhongju Ye Chen Zhang Yanjun Zhao Hai-bin Luo Lehui Xiao College of Chemistry Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Biosensing and Molecular RecognitionCollege of ChemistryNankai UniversityTianjin 300071China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China School of Pharmaceutical Science&Technology Tianjin UniversityTianjin 300072China

The progression of Alzheimer’s disease(AD)is characterized with the deposition and aggregation ofβ-amyloid(Aβ).Visualizing Aβaggregates at high spatial resolution is beneficial for AD diagnosis and ***,we designed a new molecule by conjugating corannulene(Cor)with rhodamine B isothiocyanate(Rhb),namely Cor-Rhb,for the nanoscopic imaging and modulating Aβpeptide *** low duty cycle,high photon output and sufficient switching cycles enable Cor-Rhb suitable for localization-based nanoscopic fluorescence *** find that Cor-Rhb can inhibit Aβpeptides fibrillization and interact directly with mature fibrils,triggering their disaggregation under light *** reduced Aβ-mediated cytotoxicity after the addition of Cor-Rhb is also *** explorations suggest that Cor-Rhb displays great potential as a multifunctional therapeutic agent against amyloid-related diseases,and may largely facilitate a variety of super-resolution based biological applications.

关键词： nanoscopic imaging β-amyloid reactive oxygen species fluorescence imaging fibrillation

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Hearing loss and cognitive decline among older adults with atrial fibrillation:the SAGE-AF study

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Journal of Geriatric Cardiology 2020年第4期17卷 177-183页

作者： Wei-Jia WANG Darleen Lessard Hawa Abu David D.McManus Tanya Mailhot Jerry H.Gurwitz Robert J.Goldberg Jane Saczynski Division of Cardiovascular Medicine Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterMAUSA Department of Population and Quantitative Health Sciences University of Massachusetts Medical SchoolWorcesterMAUSA Department of Pharmacy and Health System Sciences Northeastern UniversityBostonMAUSA Meyers Primary Care Institute University of Massachusetts Medical SchoolWorcesterMAUSA

Objective To examine the association between hearing loss and cognitive function cross-sectionally and prospectively among older adults with atrial fibrillation(AF).Methods Patients with AF≥65-year-old(n=1244)in the SAGE(Systematic Assessment of Geriatric Elements)-AF study were recruited from five internal medicine or cardiology clinics in Massachusetts and *** was assessed by a structured questionnaire at *** function was assessed by Montreal Cognitive Assessment(MoCA)at baseline and one *** impairment was defined as score≤23 on the *** associations between hearing loss and cognitive function were examined by multivariable adjusted logistic *** Participants with hearing loss(n=451,36%)were older,more likely to be male,and have depressive symptoms than patients without hearing *** baseline,528(42%)participants were cognitively *** with hearing loss were significantly more likely to have cognitive impairment at baseline[adjusted odds ratio(OR)=1.37,95%confidence interval(CI):1.05–1.81].Among the 662 participants who did not have cognitive impairment at baseline and attended the one-year follow-up visit,106(16%)developed incident cognitive *** with,versus those without,hearing loss were significantly more likely to develop incident cognitive impairment at one year(adjusted OR=1.68,95%CI:1.07–2.64).Conclusions Hearing loss is a prevalent but under-recognized factor associated with cognitive impairment in patients with *** for hearing loss may be indicated among these patients to identify individuals at high-risk for adverse outcomes.

关键词： Atrial fibrillation Cognitive function Hearing

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Association between body mass index and the risk of bleeding in elderly patients with non-valvular atrial fibrillation taking dabigatran:a cohort study

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Journal of Geriatric Cardiology 2020年第4期17卷 193-201页

作者： Ming-Hui LI Li-Hua HU Yu-Rong XIONG Yu YU Wei ZHOU Tao WANG Ling-Juan ZHU Xi LIU Hui-Hui BAO Xiao-Shu CHENG Department of Cardiovascular Medicine the Second Affiliated Hospital of Nanchang UniversityJiangxiChina Center for Prevention and Treatment of Cardiovascular Diseases the Second Affiliated Hospital of Nanchang UniversityJiangxiChina Center of Cardiovascular Inner Mongolia People’s HospitalHohhotInner MongoliaChina

Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI and the risk of bleeding in elderly NVAF patients taking *** A total of 509 elderly NVAF patients,who were being treated at twelve centers in China from February 2015 to December 2017 and taking dabigatran,were *** exposure and outcome variables were BMI at baseline and bleeding events within the subsequent six months,*** proportional hazards regression analysis was used to evaluate the association between BMI and the risk of ***,the Cox proportional hazards regression with cubic spline functions and smooth curve fitting was *** During the six-month follow-up,50 participants experienced *** 1 kg/m^2 increase in BMI was associated with a 12%increased risk of bleeding(P=0.021).Compared to those with BMI values in Tertile 1(25.3 kg/m^2)were 2.71(95%CI:1.02–7.17)and 3.5(95%CI:1.21–8.70),*** Ptrend-value was significant in all *** adjusted smooth curve showed a linear association between BMI and *** of the stratified variables showed significant effect modification on the association between BMI and bleeding(Pinteraction>0.05).Conclusions BMI was significantly and positively associated with the risk of bleeding in elderly NVAF patients treated with dabigatran.

关键词： Atrial fibrillation Bleeding Body mass index Dabigatran

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The impact of post-operative atrial fibrillation on outcomes in coronary artery bypass graft and combined procedures

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Journal of Geriatric Cardiology 2021年第5期18卷 319-326页

作者： Yau-Lam Alex Chau Ji Won Yoo Ho Chuen Yuen Khalid Bin Waleed Dong Chang Tong Liu Fang Zhou Liu Gary Tse Sharen Lee Ka Hou Christien Li Faculty of Pharmaceutical Sciences University of British ColumbiaBritish ColumbiaCanada Department of Medicine and Geriatrics Princess Margaret HospitalHong KongChina Department of Cardiology Fuwai Hospital Chinese Academy of Medical Sciences ShenzhenShenzhenChina Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina Xiamen Cardiovascular Hospital Xiamen UniversityXiamenChina Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjinChina Department of Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouChina Faculty of Health and Medical Sciences University of SurreyGU27ALGuildfordUnited Kingdom Cardiovascular Analytics Group Laboratory of Cardiovascular PhysiologyHong KongChina Arrowe Park Acute Stroke Unit Wirral University Teaching Hospital NHS Foundation TrustWirralUK

BACKGROUND Postoperative atrial fibrillation(POAF)is a common yet understudied clinical issue after coronary artery bypass graft(CABG)leading to higher mortality rates and *** systematic review and metaanalysis evaluated the rates of adverse outcomes between patients with and without POAF in patients treated with CABG or combined *** The search period was from the beginning of PubMed and Embase to May 18th,2020 with no language *** inclusion criteria were:(1)studies comparing new onset atrial fibrillation before or after revascularization *** new onset AF before or after *** outcomes assessed included allcause mortality,cardiac death,cerebral vascular accident(CVA),myocardial infarction(MI),repeated revascularization,major adverse cardiac event(MACE),and major adverse cardiac and cerebrovascular events(MACCEs).RESULTS Of the 7,279 entries screened,11 studies comprising of 57,384 patients were *** to nonPOAF,POAF was significantly associated with higher risk of allcause mortality(Risk Ratio(RR)=1.58;95%Confidence Interval(CI):1.42−1.76,P<0.00001)with accompanying high level of heterogeneity(I^(2)=62%).Conclusions Patients with POAF after CABG or combined procedures are at an increased risk of allcause mortality or ***,POAF after such procedures should be closely monitored and treated judiciously to minimize risk of further *** there are studies on POAF versus no POAF on outcomes,the heterogeneity suggests that further studies are needed.

关键词： bypass fibrillation mortality

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Association between big endothelin-1 and CHADS2/CHA2DS2-VASc scores in non-valvular atrial fibrillation

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Journal of Geriatric Cardiology 2019年第11期16卷 812-817页

作者： Li-Hui ZHENG Shang-Yu LIU Feng HU Er-Peng LIANG Ling-Min WU Hong-Lei WANG Ammar M Killu Yan YAO Clinical EP Lab&Arrhythmia Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangChina Department of Cardiovascular Medicine Mayo ClinicRochesterMNUSA

Background Endothelial function,as measured by big endothelin-1(ET-1),has been demonstrated to be useful in predicting adverse long-term events in patients with cardiovascular ***,there are little data about the association between big ET-1 and thromboembolism risk in atrial fibrillation(AF).We aimed to investigate the relationship between big ET-1 and CHADS2/CHA2DS2-VASc scores used for evaluating thromboembolic risk in patients with non-valvular *** The study population consisted of 238 consecutive AF patients(67.6%with paroxysmal AF and 32.4%with persistent AF).The patients were divided into two groups(high-or low-intermediate risk group)based on CHADS2 and CHA2 DS2-VASc scores(score≥2 or<2,respectively).Clinical,laboratory,and echocardiographic parameters were evaluated,and the CHADS2/CHA2DS2-VASc scores were compared between *** association between big ET-1 levels and CHADS2/CHA2DS2-VASc score was *** logistic regression analysis was performed to identify independent predictors of CHADS2/CHA2DS2-VASc *** The high CHADS2/CHA2DS2-VASc score group had older age,higher big ET-1 levels,and enlarged left atrial diameter than the low CHADS2/CHA2DS2-VASc score group(P<0.05).Multiple logistic regression analysis revealed that big ET-1 level was an independent determinant of high CHADS2/CHA2DS2-VASc scores[odds ratio(OR)=2.545 and OR=3.816;both P<0.05].Conclusions Our study indicates that in non-valvular AF,big ET-1 was significantly correlated with CHADS2/CHA2DS2-VASc scores and an independent predictor of high CHADS2/CHA2DS2-VASc *** ET-1 may serve as a useful marker for risk stratification in this setting.

关键词： Atrial fibrillation Cardiac risk factors Prevention Stroke

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Periprocedural complications and one-year outcomes after catheter ablation for treatment of atrial fibrillation in elderly patients:a nationwide Danish cohort study

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Journal of Geriatric Cardiology 2021年第11期18卷 897-907页

作者： Jesper Nielsen Kristian Hay Kragholm Sofie Brix Christensen Arne Johannessen Christian Torp-Pedersen Steen Buus Kristiansen Peter Karl Jacobsen Peter Steen Hansen Mogens Stig Djurhus Christoffer Polcwiartek Peter Søgaard Anna Margrethe Thøgersen Uffe Jakob Ortved Gang Ole Dan Jørgensen Filip Lyng Lindgren Sam Riahi Department of Cardiology Aalborg University HospitalDenmark Department of Cardiology Gentofte HospitalCopenhagen University HospitalDenmark Department of Clinical Research and Cardiology Nordsjaellands HospitalHillerødDenmark Department of Cardiology Skejby University HospitalDenmark Department of Cardiology RigshospitaletCopenhagen University HospitalDenmark Mølholm Clinic VejleDenmark Department of Cardiology Odense University hospitalDenmark Department of Cardiology Roskilde University HospitalDenmark Department of Thoracic Surgery Odense University HospitalDenmark AF-Study group Aalborg University Hospital Denmark Clinical Institute Aalborg UniversityDenmark

OBJECTIVES To investigate complications within 30-days following first-time ablation for atrial fibrillation(AF),including a composite of cardiac tamponade,hematoma requiring intervention,stroke or death,in patients≥75 years of age,compared to pa-tients aged 65−74 *** addition,one-year all-cause mortality and AF relapse were ***&RESULTS All patients receiving their first catheter ablation for AF between 2012 and 2016 were identified us-ing Danish nationwide *** aged 65−74 years served as the reference group for patients≥75 *** of AF within one year was defined as cardioversion following a three-month blanking period,re-ablation or confirmed relapse within *** composite complication outcome did not differ between the two age groups,with 39/1554(2.8%)in patients 65−74 years of age,versus 5/199(2.5%)in older patients(adjusted HR=0.94),95%CI:0.37−2.39,P=0.896).Patients≥75 years or older had no increased hazard of death within 30 days after the procedure,with an incidence of 3/1554(0.2%)in younger pa-tients and 2/199(1.0%)in patients≥75 years of age(adjusted HR=4.71,95%CI:0.78−28.40,P=0.091).There was no difference in relapse of AF after one year between age groups(≥75 years adjusted HR=1.00,95%CI:0.78-1.26,P=0.969).CONCLUSION In patients≥75 years of age selected for catheter ablation for AF,the incidence of periprocedural complica-tions,as well as one-year freedom from AF showed no statistical difference,when compared to patients 65−74 years of age.

关键词： patients fibrillation atrial

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Anticoagulation for atrial fibrillation in heart failure patients:balancing between Scylla and Charybdis

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Journal of Geriatric Cardiology 2021年第5期18卷 352-361页

作者： Grigorios Tsigkas Anastasiοs Apostolos Stefanos Despotopoulos Georgios Vasilagkos Angeliki Papageorgiou Eleftherios Kallergis Georgios Leventopoulos Virginia Mplani Ioanna Koniari Dimitrios Velissaris John Parissis Department of Cardiology University Hospital of PatrasPatrasGreece Department of Cardiology University Hospital of HeraklionHeraklionGreece Department of Cardiology University Hospital of South ManchesterNHS Foundation TrustManchesterUnited Kingdom Department of Internal Medicine University Hospital of PatrasPatrasGreece Second Department of Cardiology National and Kapodistrian University of AthensAttikon University HospitalAthensGreece

The management of heart failure(HF)and atrial fibrillation(AF)in realworld practice remains a debating issue,while the number of HF patients with AF increase *** it is unclear if rhythm or rate control therapy is more beneficial and under which circumstances,anticoagulation therapy is the cornerstone of the AFHF patients’*** antagonists were the goldstandard during the past,but currently their usage is limited in specific *** K oral anticoagulants(NOACs)have gained ground during the last ten years and considered as goldstandard of a wide spectrum of HF *** current manuscript aims to review the current literature regarding the indications and the optimal choice and usage of NOACs in HF patients with AF.

关键词： patients fibrillation vitamin

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Atrial fibrillation in older adults with cancer

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Journal of Geriatric Cardiology 2022年第1期19卷 1-8页

作者： Manish Kumar Nerea Lopetegui-Lia Christina Al Malouf Mansour Almnajam Patrick P.Coll Agnes S.Kim Department of Medicine Pat and Jim Calhoun Cardiology CenterUniversity of Connecticut School of MedicineFarmingtonCT 06030USA Department of Hematology and Oncology Cleveland ClinicOhio 44195USA De-partment of Cardiology Mount Sinai Hospital/Icahn School of MedicineNew York 10029USA Department of Fam-ily Medicine UConn Center of AgingUniversity of ConnecticutSchool of MedicineFarmingtonCT 06030USA

Cancer and atrial fibrillation(AF)are common co-morbid conditions in older *** cancer and cancer treatment increase the risk of developing new AF which increases morbidity and *** rate and rhythm control along with anticoagulation therapy remain the mainstay of treatment of AF in older adults with both cancer and *** to the treatment may be necessary because of drug interactions with concurrent *** and old age increase the risk of both,thromboembolism and *** risk of these complications is further enhanced by concomitant cancer therapy,frailty,poor nutrition status and,coexisting geriatric ***,careful attention needs to be given to the risks and benefits of using anticoagulant *** review focuses on the management of AF in older patients with cancer,including at the end-of-life care.

关键词： fibrillation Cancer chemotherapy

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The association of atrial fibrillation and dementia incidence: a meta-analysis of prospective cohort studies

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Journal of Geriatric Cardiology 2019年第3期16卷 298-306页

作者： Dao-Shen LIU Jing CHEN Wei-Ming JIAN Guang-Rong ZHANG Zhi-Rong LIU Department of Neurology Xijing Hospitalthe Fourth Military Medical UniversityXi’anShaanxiChina Department of Geriatrics Xijing Hospitalthe Fourth Military Medical UniversityXi’anShaanxiChina

Objectives To assess and synthesize the prospective cohort studies published so far on the association between atrial fibrillation (AF) and dementia *** We searched PubMed,Web of Science,and the Cochrane Library for potential studies published in English previous to April *** independent reviewers screened the search results for prospective cohort studies reporting the association between AF and dementia incidence in patients with normal cognitive function at baseline and not suffering from an acute *** Newcastle-Ottawa Scale was adopted to evaluate the quality of the included *** pooled hazard ratio (HR) of AF for dementia was calculated with the Comprehensive Meta-Analysis software,version *** and publication bias were assessed with the I2 test and funnel plot,*** We finally identified 11 prospective cohort studies covering 112,876 *** the included studies reported an adjusted HR obtained in multiple Cox regression *** qualities of the included studies ranged from moderate to *** pooled analysis with a fixed-effects model,AF was independently associated with dementia incidence (HR = 1.34,95% CI: 1.24–1.44).Subgroup analysis of studies considering anticoagulation as an important confounding factor achieved a similar *** on the I2 test and funnel plot,we did not detect obvious heterogeneity and publication bias in our ***-regression on age did not find significant *** The results of our meta-analysis further confirmed that AF was an independent risk factor for dementia in patients with normal baseline cognitive function not suffering from acute *** for dementia in AF patients and including dementia as an independent outcome in large AF treatment trials is warranted.

关键词： Atrial fibrillation Arrhythmias Cognitive impairment Dementia Meta-analysis

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