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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 *** have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human *** of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric *** 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 *** review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS *** addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS *** 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

Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai department of Neurosurgery Tongji HospitalSchool of MedicineTongji University department of Pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective ***,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently *** this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning *** found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 *** 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose ***,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved ***,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit

Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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Research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular Research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA department of medicine University of Rochester School of Medicine and DentistryRochesterNYUSA department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA department of Pathology and Laboratory medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

Intranasal administration of stem cell-derived exosomes for central nervous system diseases

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Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho Gotoh Masahito Kawabori Miki Fujimura department of Neurosurgery Hokkaido University Graduate School of MedicineHokkaidoJapan

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular *** nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive *** findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system *** exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic ***,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug ***,researchers have turned their attention to exosomes as a novel therapeutic ***,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical *** overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous *** exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain ***,exosomes,owing to their small size,can readily access the nerve pathways using this *** a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased *** this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system ***,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation

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Journal of Pharmaceutical Analysis 2024年第5期14卷 653-665页

作者： Jiani Zhong Hang Chen Qiming Liu Shenghua Zhou Zhenguo Liu Yichao Xiao department of Cardiovascular medicine Second Xiangya HospitalCentral South UniversityChangsha410011China Xiangya school of medicine Central South UniversityChangsha410008China Center for Precision medicine and Division of Cardiovascular medicine Department of MedicineSchool of MedicineUniversity of MissouriColumbiaMO65211USA

Atrial fibrillation(AF)is the most common cardiac *** medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for *** have unique metabolic characteristics to maintain adenosine triphosphate *** changes occur in myocardial metabolism in ***-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and ***-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial *** article reviews the changes in metabolic characteristics in cardiomyocytes in *** the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.

关键词： Atrial fibrillation Glucagon-like peptide-1 receptor agonists Metabolism

Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第11期30卷 1001-1006页

作者： HE Dan TAN Xiao-ning LI Lin-pei GAO Wen-hui TIAN Xue-fei ZENG Pu-hua Hunan Academy of Chinese medicine school of Integrated Chinese and Western medicine Hunan University of Chinese Medicine Scientific Research department The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine Oncology department The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine school of Traditional Chinese medicine Hunan University of Chinese Medicine

Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer ***:Breast cancer 4T1 cells were divided into 6 groups:control,brazilin 1/2 half maximal inhibitory concentration(IC50),IC50,2×IC50,erastin（10 μg/mL） and capecitabine（10 μg/mL） *** effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay,and the treatment dose of brazilin was *** effect of brazilin on the mitochondrial morphology of 4T1 cells,and the mitochondrial damage was evaluated under electron *** levels of Fe2+,reactive oxygen species（ROS）,malondialdehyde（MDA）,glutathione（GSH） and glutathione peroxidase 4（GPX4） were estimated using various detection *** invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell *** expressions levels of tumor protein p53, solute carrier family 7 member 11（SLC7A11）,GPX4 and acyl-CoA synthetase long-chain family member 4（ACSL4） proteins were quantified by Western blot ***:Compared to the control group,the 10(1/2 IC50),20(IC50) and 40(2×IC50) μg/mL brazilin,erastin,and capecitabine groups showed a significant decrease in the cell survival rate,invasion and migration abilities,GSH,SLC7A11 and GPX4 protein expression levels,and mitochondrial volume and ridge（P<0.05）,and a significant increase in the mitochondria membrane density,Fe2+,ROS and MDA levels,and p53 and ACSL4protein expression levels（P<0.05）.Conclusions:Brazilin actuated ferroptosis in breast cancer cells,and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

关键词： Chinese medicine brazilin breast cancer ferroptosis p53/SLC7A11/GPX4 axis

Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers

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World Journal of Emergency medicine 2024年第1期15卷 3-9页

作者： Rashed Alremeithi Quincy K.Tran Megan T.Quintana Soroush Shahamatdar Ali Pourmand department of Emergency medicine George Washington University School of Medicine and Health SciencesWashington DC 20037USA department of Emergency medicine University of Maryland School of MedicineBaltimore 21201USA Program in Trauma the R Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimore 21201USA Center for Trauma and Critical Care Department of Surgerythe George Washington University School of Medicine&Health SciencesWashington DC 20037USA

BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare *** there have been advances in treatment modalities,survival rates for TCA patients remain *** narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating ***:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,*** search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English *** the search,943 articles were retrieved,and two independent reviewers conducted a screening ***:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable *** were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital *** thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt *** endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic *** implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality ***-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,*** the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ***:TCA remains a signifi cant challenge for emergency medical services due to its high m

关键词： Traumatic cardiac arrest Emergency thoracotomy Resuscitative endovascular balloon occlusion of the aorta

Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

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World Journal of Emergency medicine 2024年第2期15卷 142-146页

作者： Yi Gu Xiandong Liu Tiancao Dong Qian Yang Xiaowei Bao Dongyang Zhao Lunxian Tang department of Internal Emergency medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China school of medicine Tongji UniversityShanghai 200120China

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune *** was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May ***,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

关键词： encephalitis autoimmune aspartate

Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

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BIOCELL 2024年第1期48卷 1-8页

作者： YU LIU ROBERT J.KASPER NATALIE J.S.CHOI department of Family and Community medicine Northwestern University Feinberg School of MedicineChicagoIllinois

Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological *** evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected *** disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ *** the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with *** studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 *** addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 *** review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

关键词： Extracellular vesicles COVID-19 Angiotensin converting enzyme 2 Thimet oligopeptidase