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Music as medicine for traumatic brain injury:a perspective on future research directions

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Neural Regeneration Research 2024年第10期19卷 2105-2106页

作者： Anthony E.Kline Eleni H.Moschonas Corina O.Bondi Department of Physical medicine&Rehabilitation University of PittsburghPittsburghPAUSA Safar Center for Resuscitation Research University of PittsburghPittsburghPAUSA Center for Neuroscience University of PittsburghPittsburghPAUSA Department of Critical Care medicine University of PittsburghPittsburghPAUSA Center for the Neural Basis of Cognition University of PittsburghPittsburghPAUSA Department of Psychology University of PittsburghPittsburghPAUSA Department of Neurobiology University of PittsburghPittsburghPAUSA

Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.

关键词： injury traumatic

High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke P.Lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various diseases.However,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities.Here,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets.By adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet.We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid biopsies.Due to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： Shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano Department of Orthopedic Surgery Keio University School of Medicine Department of Physiology Keio University School of Medicine

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen Department of Ophthalmology School of MedicineUniversity of Missouri Department of Biomedical Sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body.They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases.Some of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric disorders.In addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS diseases.This review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies.In addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases.Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

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Journal of Sport and Health Science 2024年第5期13卷 621-630页

作者： Yujia(Susanna)Qiao Terri L.Blackwell Peggy M.Cawthon Paul M.Coen Steven R.Cummings Giovanna Distefano Samaneh Farsijani Daniel E.Forman Bret H.Goodpaster Stephen B.Kritchevsky Theresa Mau Frederico G.S.Toledo Anne B.Newman Nancy W.Glynn Department of Epidemiology School of Public HealthUniversity of PittsburghPittsburghPA 15261USA San Francisco Coordinating Center California Pacific Medical Center Research InstituteSan FranciscoCA 94143USA Department of Epidemiology and Biostatistics University of CaliforniaSan FranciscoCA 94143USA Translational Research Institute AdventHealthOrlandoFL 32804USA Department of medicine(Geriatrics and Cardiology) University of Pittsburghand GeriatricsResearchEducationand Clinical Center(GRECC)VA Pittsburgh Healthcare SystemPittsburghPA 15261USA Department of Internal medicine Section on Gerontology and Geriatric MedicineWake Forest School of MedicineWinston-SalemNC 27109USA Division of Endocrinology and Metabolism Department of MedicineUniversity of PittsburghPittsburghPA 15261USA

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associatio

关键词： Aging Exercise Mitochondria

Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou school of Traditional Chinese medicine Beijing University of Chinese Medicine

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol(LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor(LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9(PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

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World Journal of Gastroenterology 2024年第9期30卷 1011-1017页

作者： Chun-Cheng Chiang Hsuan Yeh Ruei-Feng Shiu Wei-Chun Chin Tzung-Hai Yen school of medicine University of PittsburghPittsburghPA 15213United States pittsburgh Liver Research Center University of PittsburghPittsburghPA 15213United States Division of Experimental Pathology Department of PathologyUniversity of PittsburghPittsburghPA 15213United States Division of Endocrinology Department of PediatricsUniversity of PittsburghPittsburghPA 15213United States Center of Excellence for The Oceans National Taiwan Ocean UniversityKeelung 20224Taiwan Institute of Marine Environment and Ecology National Taiwan Ocean UniversityKeelung 20224TaiwanChina Department of Materials Science and Engineering University of California MercedMercedCA 95343United States Department of Nephrology Clinical Poison CenterChang Gung Memorial HospitalTaoyuan 333TaiwanChina College of medicine Chang Gung UniversityTaoyuan 333TaiwanChina

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

关键词： Microplastics Nanoplastics Liver Reactive oxidative species Cell death Autophagy Innate immunity Metabolic dysfunction-associated fatty liver disease Gut-liver axis

Omics approaches in asthma research:Challenges and opportunities

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Chinese Medical Journal Pulmonary and Critical Care medicine 2024年第1期2卷 1-9页

作者： Molin Yue Shiyue Tao Kristina Gaietto Wei Chen Department of Biostatistics School of Public HealthUniversity of PittsburghPittsburghPA 15224USA Division of Pediatric Pulmonary medicine UPMC Children’s Hospital of PittsburghUniversity of PittsburghPittsburghPA 15224USA

Asthma,a chronic respiratory disease with a global prevalence of approximately 300 million individuals,presents a significant societal and economic burden.This multifaceted syndrome exhibits diverse clinical phenotypes and pathogenic endotypes influenced by various factors.The advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying mechanisms.Omics technologies are employed to systematically screen for potential biomarkers,encompassing genes,transcripts,methylation sites,proteins,and even the microbiome components.This review provides an insightful overview of omics applications in asthma research,with a special emphasis on genetics,transcriptomics,epigenomics,and the microbiome.We explore the cutting-edge methods,discoveries,challenges,and potential future directions in the realm of asthma omics research.By integrating multi-omics and non-omics data through advanced sta-tistical techniques,we aspire to advance precision medicine in asthma,guiding diagnosis,risk assessment,and personalized treatment strategies for this heterogeneous condition.

关键词： Asthma Genomics Transcriptomics Epigenomics Metagenomics Multi-omics integration

Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern Chinese medicine Resources Chengdu University of Traditional Chinese Medicine school of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin