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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Frailty in patients undergoing transcatheter aortic valve replacement:from risk scores to frailty-based management

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Journal of Geriatric cardiology 2021年第6期18卷 479-486页

作者： Andreas Tzoumas Damianos G.Kokkinidis Stefanos Giannopoulos George Giannakoulas Leonidas Palaiodimos Dimitrios V Avgerinos Polydoros N Kampaktsis Robert T.Faillace Aristotle university of Thessaloniki ThessalonikiGreece Department of Medicine Jacobi Medical CenterAlbert Einstein College of MedicineBronxUSA division of cardiology Rocky Mountain Regional VA Medical CenterUniversity of ColoradoDenverUSA First cardiology.Department AHEPA University HospitalAristotle University of ThessalonikiThessalonikiGreece division of Hospital Medicine Montefiore Medical CenterAlbert Einstein College of MedicineBronxUSA Department of Cardiothoracic Surgery New York-Presbyterian/Weill Cornell Medical CenterNew YorkUSA division of cardiology New York University Langone Medical CenterNew YorkUSA

Aortic stenosis(AS)is the most common valvular disease in the western coun-tries and is associated with aging.[1,2]Transcatheter aortic valve replacement(TAVR)now offers a therapeutic option for elderly patients who are deemed inoperable and is an excellent alternative for those who are considered high-risk for surgical valve replacement.[3,4]However,mortality after TAVR is still high with one-year and two-year mortality rates of 24.3%and 33.9%,respectively.[5]Thus,util-ization of effective risk stratification tools before TAVR cannot be overstated.

关键词： mortality patients aortic

维普期刊数据库

ST-segment elevation myocardial infarction in Kawasaki disease:A case report and review of literature

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World Journal of Clinical Cases 2022年第26期10卷 9368-9377页

作者： Joonpyo Lee Jeongduk Seo Yong Hoon Shin Albert Youngwoo Jang Soon Yong Suh division of cardiology Department of Internal MedicineGachon UniversityGil Medical CenterIncheon 21565South Korea

BACKGROUND Kawasaki disease(KD)is an acute self-limiting febrile vasculitis that occurs during childhood and can cause coronary artery aneurysm(CAA).CAAs are associated with a high rate of adverse cardiovascular *** SUMMARY A Korean 35-year-old man with a 30-year history of KD presented to the emergency room with chest *** coronary angiography was performed as ST-segment elevation in the inferior leads was observed on the *** aneurysm of the left circumflex(LCX)coronary artery was found with massive thrombi within.A drug-eluting 4.5 mm 23 mm-sized stent was inserted into the occluded area without *** maximal diameter of the LCX was 6.0 mm with a Z score of 4.7,suggestive of a small aneurysm considering his age,sex,and body surface *** further present a case series of 19 patients with KD,including the current patient,presenting with acute coronary syndrome(ACS).Notably,none of the cases showed Z scores;only five patients(26%)had been regularly followed up by a physician,and only one patient(5.3%)was being treated with antithrombotic therapy before ACS *** For KD presenting with ACS,regular follow up and medical therapy may be crucial for improved outcomes.

关键词： Kawasaki disease Acute coronary syndrome ST elevation myocardial infarction Coronary angiography Percutaneous coronary intervention Case report

Robotics in genital gender-affirming surgery

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Plastic and Aesthetic Research 2023年第1期10卷 74-82页

作者： Brielle Weinstein Henry Govekar Edward Cherullo Kristin M.Jacobs Loren Schechter Department of Surgery Division of Plastic and Reconstructive SurgeryRush University Medical CenterChicagoIL 60612USA Department of Surgery Division of Colorectal SurgeryRush University Medical CenterChicagoIL 60612USA Department of Urology Rush University Medical CenterChicagoIL 60612USA Department of Surgery Division of Plastic and Reconstructive SurgeryDepartment of Obstetrics and GynecologyRush University Medical CenterChicagoIL 60612USA

Gender-affirming genital surgery includes a constellation of pelvic procedures that can help feminize or masculinize the *** advances in robotic surgery can aid surgical access to and visualization of the pelvis,thereby facilitating certain *** this scoping review,we will discuss the developing role of the robot in genital affirming genital ***,techniques,and outcomes using the robot in both feminizing and masculinizing genital procedures will be reviewed.

关键词： Robotic surgery gender affirming surgery vaginoplasty peritoneal vaginoplasty intestinal vaginoplasty metoidioplasty colpectomy vaginectomy phalloplasty

Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment

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Microsystems & Nanoengineering 2022年第2期8卷 135-147页

作者： Muhammad R.Haque Caitlin R.Wessel Daniel D.Leary Chengyao Wang Abhinav Bhushan Faraz Bishehsari division of Digestive Diseases Rush Center for Integrated Microbiome&Chronobiology ResearchRush University Medical CenterChicagoIL 60612USA university of Louisville School of Medicine LouisvilleKT 40202USA Department of Biomedical Engineering Illinois Institute of TechnologyChicagoIL 60616USA

The patient population suffering from pancreatic ductal adenocarcinoma(PDAC)presents,as a whole,with a high degree of molecular tumor *** heterogeneity of PDAC tumor composition has complicated treatment and stalled success in clinical *** in vitro techniques insufficiently replicate the intricate stromal components of PDAC tumor microenvironments(TMEs)and fail to model a given tumor's unique genetic *** development of patient-derived organoids(PDOs)has opened the door for improved personalized medicine since PDOs are derived directly from patient tumors,thus preserving the tumors'unique behaviors and genetic *** study developed a tumor-chip device engineered to mimic the PDAC TME by incorporating PDOs and stromal cells,specifically pancreatic stellate cells and *** PDOs in a multicellular microfluidic chip device prolongs cellular function and longevity and successfully establishes a complex organotypic tumor environment that incorporates desmoplastic stroma and immune *** primary cancer cells in monoculture were subjected to stroma-depleting agents,there was no effect on cancer cell ***,targeting stroma in our tumor-chip model resulted in a significant increase in the chemotherapy effect on cancer cells,thus validating the use of this tumor-chip device for drug testing.

关键词： cancer chemotherapy adenocarcinoma

Left and right ventricular diastolic dysfunction and diastolic heart failure: does one lead to the other?

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Journal of Geriatric cardiology 2009年第1期6卷 3-10页

作者： Faramarz Tehrani Anita Phan Ernst R. Schwarz division of cardiology Department of Medicine Cedars-Sinai Medical Center and University of California Los Angeles Los Angeles California Division of Cardiology Department of Medicine Cedars-Sinai Medical Center and University of California Los Angeles Los Angeles California Division of Cardiology Department of Medicine Cedars-Sinai Medical Center and University of California Los Angeles Los Angeles California

Background and Objective Diastolic dysfunction of the left ventricle is a mechanical abnormality diagnosed primarily by echocardiogram, and can be distinguished into three separate degrees based on the severity of reduction in passive compliance and active myocardial relaxation. Methods A literature search was performed for basic science studies, clinical studies and major practice guidelines on the subject of diastolic dysfunction and diastolic heart failure. Important findings were analyzed and correlated with regard to clinical relevance. Results Left ventricular diastolic dysfunction appears to compromise exercise tolerance and is believed to contribute to the pathophysiology in patients with diastolic heart failure. In the clinical setting, however, oftentimes no clear distinction is made between echocardiographically diagnosed diastolic dysfunction and diastolic heart failure, and adequate treatment recommendations are sparse and aimed to prevent worsening and progression of clinical symptoms. To date, there is a lack of high powered trials assessing the possible progression rate from echocardiographically diagnosed diastolic dysfunction to the clinical diagnosis of diastolic heart failure. Furthermore, there are no solid indices to assess the degree of severity of diastolic dysfunction or its progression. Pure right ventricular diastolic dysfunction appears to be even less understood and under-recognized, although it may play a role in the development of both right and left heart failure. Currently there are few but interesting data on the possible interaction between ventricles with diastolic dysfunction and the overall affect on the development of heart failure. Conclusions The timeline and progression of diastolic dysfunction to diastolic heart failure have not been well established and warrant further investigation.

关键词： Diastolic dysfunction diastolic heart failure left ventricular dysfunction heart failure cardiomyopathy

Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Comparison of long-term outcome between patients aged 〈 65 years vs. ≥ 65 years after atrial fibrillation ablation

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Journal of Geriatric cardiology 2017年第9期14卷 569-574页

作者： Zsuzsanna Kis Anna ME Noten Mihran Martirosyan Astrid A Hendriks Rohit Bhagwandien Tamas Szili-Torok Department of cardiology Erasmus MC University Medical Center Rotterdam the Netherlands

Background Atrial fibrillation （AF） is the most frequent arrhythmia, and its prevalence is increasing with aging. We aimed to com-pare the long-term outcome data of patients 〈 65 years vs.≥ 65 years who underwent catheter ablation （CA） for drug-refractory AF. MethodsConsecutive patients with primary pulmonary vein isolation performed between March 2001 and December 2011, and those who completeda five-year of follow-up were divided into two groups： patients aged 〈 65 years into group 1, and patients aged ≥ 65 into group 2. Long-termoutcome data concerning mortality, thromboembolic events （TE） and success rates were compared between these groups. Results A totalnumber of 390 patients were included, group 1 contained 310 patients, and 80 patients in group 2. In group 2, patients had more often impairedrenal function （P 〈 0.001） and thyroid disease （P = 0.047）. A total of fifteen patients died during the 6.63 ± 2.1 years of follow-up, with a sig-nificantly higher incidence in the older group （8/80 vs. 7/310 patients, P = 0.004）. The majority of fatal outcome was due to cancerous dis-eases in both groups. No difference was observed concerning the long-term TE rate （12/310 vs. 4/80 patients, P = 0.75）. Rhythm controlfailed in 25.9% of the patients, with no difference between the groups： 26.4% in group 1 vs. 23.7% in group 2 （P = 0,67）, ConclusionsDespite growing prevalence of AF in aging population, the elderly patients are underrepresented in CA procedures. Similar clinical successand TE complication rate are observed between the age-groups. Our data suggest more liberal criteria might be applied while selecting pa-tients for AF ablation.

关键词： Atrial fibrillation Catheter ablation Clinical outcome The elderly Thromboembolic complication

Systolic and Diastolic Strain Measurements Show Left Ventricular Dysfunction in Women with Turner Syndrome

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Congenital Heart Disease 2021年第4期16卷 357-368页

作者： Allard T.van den Hoven Sultan Yilmazer Lidia R.Bons Roderick W.Jvan Grootel L.W.Geenen An M.van Berendoncks Anthonie L.Duijnhouwer Hans-Marc J.Siebelink Jolien W.Roos-Hesselink Annemien E.van den Bosch Department of Congenital cardiology Erasmus MCRotterdamNetherlands Department of cardiology Radboud University Medical CenterNijmegenNetherlands Department of cardiology Leiden University Medical CenterRotterdamNetherlands

Aim:This study aimed to describe the systolic left ventricular global longitudinal strain(LvGLS)and left ventricular peak early diastolic strain rate(Sre)in adult women with Turner syndrome(TS)and to determine its relationship with exercise capacity and clinical ***:In this cross-sectional cohort study,consecutively included adult TS women underwent an electrocardiogram,transthoracic echocardiogram(TTE)and cardiopulmonary exercise test(CPET)on the same *** and Sre were measured using 2D speckle tracking analysis(STE)and compared with age-matched healthy female ***:Ninety-four adult women(age 36±13 years)with TS and 32 healthy age-matched female controls were *** with TS had a significantly impaired/reduced systolic LvGLS(–17.82±2.98%vs.–21.80±1.85%,p0.001),compared to healthy female ***,TS women had reduced diastolic function as measured by conventional echocardiographic parameters:A higher A-wave(p<0.001),lower E/A-ratio(p=0.001),longer deceleration time(p=0.006),and a higher E/E’-ratio(p<0.001).Women with TS also had a significantly reduced maximal workload(p=0.033),reduced oxygen uptake(p<0.001)and a reduced maximal heart rate(p<0.001)during *** linear regression analysis revealed that Age,karyotype and QT-duration were significantly associated with Sre,but not with LvGLS,in the TS ***:Systolic and diastolic strain and exercise capacity were significantly reduced in TS women compared to healthy *** correlation between strain itself and exercise capacity could be demonstrated,but correlations with conventional TTE parameters and baseline characteristics were found.

关键词： Turnersyndrome speckletracking echocardiography strain exercise capacity