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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Diabetes mellitus and glymphatic dysfunction:Roles for oxidative stress,mitochondria,circadian rhythm,artificial intelligence,and imaging

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World Journal of Diabetes 2025年第1期16卷 39-48页

作者： Kenneth Maiese National heart Lungand Blood InstituteNational Institutes of HealthBethesdaMD 20810United States

Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the *** represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately *** cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm *** pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic *** studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.

关键词： Artificial intelligence Circadian rhythm Clock genes Diabetes mellitus magnetic resonance imaging Glymphatic pathway Mitochondria Oxidative stress Programmed cell death Sleep fragmentation

Elevated serum uric acid level as a predictor for cardiovascu-lar and all-cause mortality in Chinese patients with high cardiovascular risk

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Journal of Geriatric Cardiology 2008年第1期5卷 15-20页

作者： Yongquan Wu Meijing Li Jue Li Yingyi Luo Yan Xing Dayi Hu heart Lung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China

Objective To assess the predictive value of serum uric acid levels for cardiovascular and all-cause mortality in a large prospective population based *** The study was based on 3648 participants in Shanghai and Beijing,who were inpatients with high cardiovascular(CV) risk at baseLine (2004.7 to 2005.1),and blood was ***-up for death from cardiovascular disease and any cause was complete until January 1,*** The mean follow-up was 1 *** were 303 deaths during follow-up,of which 121 were *** mortality rates were 8.3 % for all patients,6.8% for female patients (116/1715),and 9.7% (187/1933) for male *** men,patients in the lower and higher uric acid groups had increased cardiac and overall mortality risks compared with patients in the normal uric acid *** relation was found in women but not statistically *** adjusting for other conventional risk factors (age,diabetes,hypertension,diuretic use and smoking),baseline uric acid level was still associated with increased risk for death from cardiovascular disease (P=0.005),or death from all causes (P=0.014) Conclusion Our data suggest that abnormal serum uric acid levels are independently and significantly associated with risk of cardiovascular and all-cause mortality.(J Geriatr Cardiol 2008;5:15-20)

关键词： epidemiology uric acid cardiovascular mortality all-cause mortality

Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA

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Genomics, Proteomics & Bioinformatics 2017年第3期15卷 177-186页

作者： Iain M.Dykes Costanza Emanueli School of Clinical Sciences University of Bristol National heart and lung Institute Imperial College London

Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA （lncRNA）, a heteroge- neous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA （miRNA） pathways, lncRNA has been shown to act as both a source and an inhi- bitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying com- plexes by directing them to specific loci.

关键词： Long non-coding RNA MicroRNA Transcriptional regulation Epigenetics Post-transcriptionalregulation

i2dash:Creation of Flexible,Interactive,and Web-based Dashboards for Visualization of Omics Data

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 568-577页

作者： Arsenij Ustjanzew Jens Preussner Mette Bentsen Carsten Kuenne Mario Looso Max Planck Institute for heart and lung Research Bioinformatics UnitD-61231 Bad NauheimGermany

Data visualization and interactive data exploration are important aspects of illustrating complex concepts and results from analyses of omics data.A suitable visualization has to be intuitive and ***-based dashboards have become popular tools for the arrangement,consolidation,and display of such ***,the combination of automated data processing pipelines handling omics data and dynamically generated,interactive dashboards is poorly ***,we present i2dash,an R package intended to encapsulate functionality for the programmatic creation of customized *** supports interactive and responsive(linked)visualizations across a set of predefined graphical layouts.i2dash addresses the needs of data analysts/software developers for a tool that is compatible and attachable to any R-based analysis pipeline,thereby fostering the separation of data visualization on one hand and data analysis tasks on the other *** addition,the generic design of i2dash enables the development of modular extensions for specific *** a proof of principle,we provide an extension of i2dash optimized for single-cell RNA sequencing analysis,supporting the creation of dashboards for the visualization needs of such *** with these features,i2dash is suitable for extensive use in large-scale sequencing/bioinformatics *** this line,we provide i2dash as a containerized solution,enabling a straightforward large-scale deployment and sharing of dashboards using cloud services.i2dash is freely available via the R package archive CRAN(https://***/package=i2dash).

关键词： Data visualization Dashboard Cloud Data analysis Automation

Extracorporeal membrane oxygenation versus cardiopulmonary bypass during transcatheter aortic valve implantation: a meta-analysis of survival benefits

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World Journal of Emergency Medicine 2024年第4期15卷 306-310页

作者： Huiruo Liu Liangshan Wang Xing Hao Zhongtao Du Chenglong Li Hong Wang Xiaotong Hou centre for Cardiac Intensive Care Beijing Institute of HeartLung and Blood Vessel DiseasesBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Since its approval by the Food and Drug Administration in 2011,transcatheter aortic valve implantation(TAVI)has rapidly evolved to become the preferred ultimate intervention for high-and intermediate-risk patients with severe symptomatic aortic stenosis.[1]This is due to its non-open-heart,minimally invasive and off-pump advantages.[1]Nevertheless,as a result of the frequent frailty and comorbidity profiles of patients undergoing TAVI,such as advanced cardiac dysfunction and extensive coronary artery disease,or technically difficult anatomy for the procedure itself,[2-4]it is common for these patients to experience critical circulatory collapse *** factors are linked to elevated mortality rates,necessitating suitable mechanical circulatory support(MCS)to reverse the disastrous situations.[5]

关键词： anatomy bypass elevated

Pacemaker mimicking a tunnel digger

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Journal of Geriatric Cardiology 2020年第8期17卷 528-529页

作者： Matthaios V.Didagelos Dimitrios Afendoulis Petros Voutas Athanasios N.Kartalis Interventional Cardiology Department West of Scotland Heart and Lung CentreGolden Jubilee National HospitalClydebankUnited Kingdom Cardiology Department "Skylitseio"General Hospital of ChiosGreece

An 81-year-old woman was admitted to our cardiology clinic with episodes of atypical chest *** had a personal history of hypertension and had undergone implantation of a VVIR pacemaker(in a subcutaneous pocket at the right upper side of her thorax)fifteen years before at another institution,because of atrioventricular conduction disturbances(Figure 1DI).

关键词： Arrhythmias Complications Erosion Infection Pacemaker

Atg7 in development and disease： panacea or Pandora＇s Box？

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Protein & Cell 2015年第10期6卷 722-734页

作者： Jianhua Xiong Center for Molecular Medicine National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892USA

Macroautophagy is an evolutionarily conserved intracellular degradation system used by life ranging from yeasts to mammals. The core autophagic machinery is composed of ATG （autophagy-related） protein constituents. One particular member of the ATG protein family, Atg7, has been the focus of recent research. Atg7 acts as an Ellike activating enzyme facilitating both microtubule-associated protein light chain 3 （LC3）- phosphatidylethanolamine and ATG12 conjugation. Thus, Atg7 stands at the hub of these two ubiquitin-like systems involving LC3 and Atg12 in autophagic vesicle expansion. In this review, I focus on the pleiotropic function of Atg7 in development, maintenance of health, and alternations of such control in disease.

关键词： autophagy Atg7 mouse model,development disease

Protective Effect of Hydroxysafflor Yellow A on Inflammatory Injury in Chronic Obstructive Pulmonary Disease Rats

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Chinese Journal of Integrative Medicine 2019年第10期25卷 750-756页

作者： JIN Ming XUE Chang-jiang WANG Yu DONG Fang PENG Yuan-yuan ZHANG Ya-dan ZANG Bao-xia TAN Li Department of Pharmacology Beijing Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Diseases

Objective: To investigate the attenuating effect of Hydroxysafflor yellow A(HSYA) on inflammatory injury in chronic obstructive pulmonary disease(COPD). Methods: Rats were randomly assigned to 7 groups according to body weight including normal control group, HSYA blank group(76.8 mg/kg), COPD group, COPD+HSYA(30, 48, 76.8 mg/kg) groups and COPD+dexamethasone(2 mg/kg), 10 in each group. Passive cigarette smoke and intratracheal instil ation of lipopolysaccharides were used to establish a COPD model in rats. Hematoxylin and eosin staining of lung tissue sections was used, real-time polymerase chain reaction(PCR) was used to assay m RNA levels of some cytokines in lung tissues, the cytokines in bronchoalveolar lavage fluid(BALF) were measured by enzyme-linked immunosorbent assay(ELISA), Western blot analysis was used to determine phosphorylated p38 mitogen-activated protein kinase(MAPK) levels in lung tissues, and nuclear factor-κB(NF-κB) p65 protein levels in lung tissues were detected by immunohistochemistry. Results: lung alveolar septa destruction, alveolus fusion, inflammatory cel infiltration, and bronchiole exudation were observed. These pathological changes were al eviated in the COPD+HSYA group. The m RNA expression of inflammatory factors were significantly increased in lung tissues from COPD rats(all Plung tissues of COPD rats were significantly increased(al Plungs of COPD rats. HSYA could inhibit inflammatory cytokine expression, and increase phosphorylation of p38 MAPK and NF-κB p65 in the lungs of COPD rats. The protective mechanism of HSYA to inhibit COPD i

关键词： Hydroxysafflor yellow A chronic obstructive pulmonary disease inflammation p38 mitogenactivated protein kinase nuclear factor-κB