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Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe Chen Kai Wang Jie Ju Xue Yu Wanpeng Yu Cuiyun Liu Yin Wang Institute for Translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China college of medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and repair.The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal.With the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction.It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial infarction.However,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further explained.It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration.Here,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration.In addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation.Ultimately,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

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Autophagy in neural stem cells and glia for brain health and diseases

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Neural Regeneration Research 2024年第4期19卷 729-736页

作者： Aarti Nagayach Chenran Wang Department of Cancer Biology University of Cincinnati College of Medicine

Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.

关键词： astrocyte autophagy glia microglia neural stem cells neurodegenerative diseases neurodevelopmental disorders oligodendrocyte

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Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： Caleb A.Wood Nicholas M.Tran Department of Neuroscience Baylor College of MedicineHoustonTXUSA Department of Molecular and Human Genetics Baylor College of MedicineHoustonTXUSA

A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

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Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 353-360页

作者： Seogsong Jeong Sun Jae Park Seong Kyun Na Sang Min Park Byung-Cheol Song Yun Hwan Oh Department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea Department of Biomedical Informatics CHA University School of MedicineCHA UniversitySeongnam 13488Korea Department of Internal medicine Inje University College of MedicineSeoul 50834Korea Department of Family medicine Seoul National University HospitalSeoul National University College of MedicineSeoul 03080Korea Department of Internal medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family medicine Chung-Ang University Gwangmyeong HospitalChung-Ang University College of MedicineGwangmyeong 14353Korea

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

关键词： Nonalcoholic fatty liver disease Fatty liver index Hepatic steatosis index

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Mediating effect of resilience on the relationship between rumination and suicide attempts in Chinese adolescents with mood disorders

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General Psychiatry 2024年第2期37卷 306-310页

作者： Dianying Liu Gang Lei Hongdong Deng Xiangyang Zhang Yonghui Dang college of medicine&forensics Xi'an Jiaotong University Health Science CenterXi'anShaanxiChina Ganzhou City Key Laboratory of Mental Health The Third People's Hospital of Ganzhou CityGanzhouJiangxiChina Institute of Psychology Chinese Academy of SciencesBeijingChina

To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,2 and over 500000 adolescent SA are reported annually in the USA due to depression.3 Risk factors for SA include gender,hormone levels,family conflict and,particularly,negative cognitive styles such as rumination.

关键词： adolescent disorders annually

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Vanillylacetone attenuates cadmium chloride-induced hippocampal damage and memory loss through upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression

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Neural Regeneration Research 2024年第12期19卷 2750-2759页

作者： Fahaid H.A.L-Hashem Salah O.Bashir Amal F.Dawood Moutasem S.Aboonq Ismaeel Bin-Jaliah Abdulaiziz M.Al-Garni Mohamed D.Morsy Department of Physiology College of MedicineKing Khalid UniversityAbhaSaudi Arabia Department of Basic Medical Sciences College of MedicinePrincess Nourah bint Abdulrahman UniversityP.O.Box 84428Riyadh 11671Saudi Arabia Department of Physiology College of MedicineTaibah UniversityAl-Madinah Al-MunawwarahSaudi Arabia Department of medicine College of MedicineKing Khalid UniversityAbhaSaudi Arabia

Memory loss and dementia are major public health concerns with a substantial economic burden.Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment.To investigate whether the antioxidant and anti-inflammatory compound vanillyla cetone(zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride(CdCl_(2)) administration in rats,we explo red the potential involvement of the nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway,which is known to modulate oxidative stress and inflammation.Sixty healt hy male Wistar rats were divided into five groups:vehicle-treated(control),vanillylacetone,CdCl_(2),vanillylacetone+ CdCl_(2),vanillylacetone+ CdCl_(2)+ brusatol(a selective pharmacological N rf2inhibitor) groups.Vanillylacetone effectively attenuated CdCl_(2)-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test.Additionally,vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers(interleukin-6,tumor necrosis factor-α,intracellular cell adhesive molecules) and apoptosis biomarkers(Bax and cleaved caspase-3).The control and CdCl_(2)-treated groups treated with va nillylacetone showed reduced generation of reactive oxygen species,decreased malondialdehyde levels,and increased superoxide dismutase and glutathione activities,along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue.All the protective effects of vanillylacetone we re substantially blocked by the co-administration of brusatol(a selective N rf2 inhibitor).Va nillylacetone mitigated hippocampal damage and memory loss induced by CdCl_(2),at least in part, by activating the nuclear transcription factor Nrf2.Additionally,vanillylacetone exerted its potent antioxidant and antiinflammatory actions.

关键词： hippocampus neuroprotective Nrf2 gene oxidative stress vanillylacetone

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Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

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Journal of Animal Science and Biotechnology 2024年第1期15卷 236-252页

作者： Zhaoqi He Caijun Zhao Yuhong He Zhuoyu Liu Guyue Fan Kun Zhu Yiqi Wang Naisheng Zhang Yunhe Fu Xiaoyu Hu Department of Clinical Veterinary medicine College of Veterinary MedicineJilin UniversityChangchun 130062Jilin ProvinceChina

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully clarified.Recently,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(S.maltophilia)was significantly increased in both the rumen and milk microbiota.Accordingly,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary gland.Therefore,this study investigated the mechanism by which enterogenic S.maltophilia induces mastitis.Results First,S.maltophilia was labelled with superfolder GFP and administered to mice via gavage.The results showed that treatment with S.maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal leakage.Furthermore,tracking of ingested S.maltophilia revealed that S.maltophilia could migrate from the gut to the mammary gland and induce mastitis.Subsequently,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S.maltophilia.Then,using mouse mammary epithelial cells(MMECs),we verified that S.maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusions In conclusion,the results showed that enterogenic S.maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis.Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

关键词： Calcium-ROS-AMPK-mTOR-autophagy pathway Gut-mammary axis Mastitis S.maltophilia

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Performance of the EDACS-ADP incorporating high-sensitivity troponin assay:Do components of major adverse cardiac events matter?

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World Journal of Emergency medicine 2024年第3期15卷 175-180页

作者： Yedalm Yoo Shin Ahn Bora Chae Won Young Kim Department of Emergency medicine Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea

BACKGROUND:The accelerated diagnostic protocol(ADP)using the Emergency Department Assessment of Chest pain Score(EDACS-ADP),a tool to identify patients at low risk of a major adverse cardiac event(MACE)among patients presenting with chest pain to the emergency department,was developed using a contemporary troponin assay.This study was performed to validate and compare the performance of the EDACS-ADP incorporating high-sensitivity cardiac troponin I between patients who had a 30-day MACE with and without unstable angina(MACE I and II,respectively).METHODS:A single-center prospective observational study of adult patients presenting with chest pain suggestive of acute coronary syndrome was performed.The performance of EDACS-ADP in predicting MACE was assessed by calculating the sensitivity and negative predictive value.RESULTS:Of the 1,304 patients prospectively enrolled,399(30.6%;95%confidence interval[95%CI]:27.7%–33.8%)were considered low-risk using the EDACS-ADP.Among them,the rates of MACE I and II were 1.3%(5/399)and 1.0%(4/399),respectively.The EDACS-ADP showed sensitivities and negative predictive values of 98.8%(95%CI:97.2%–99.6%)and 98.7%(95%CI:97.0%–99.5%)for MACE I and 98.7%(95%CI:96.8%–99.7%)and 99.0%(95%CI:97.4%–99.6%)for MACE II,respectively.CONCLUSION:EDACS-ADP could help identify patients as safe for early discharge.However,when unstable angina was added to the outcome,the 30-day MACE rate among the designated lowrisk patients remained above the level acceptable for early discharge without further evaluation.

关键词： Chest pain Major adverse cardiac event Acute coronary syndrome Emergency department

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Self-adhesive pads in defi brillation or cardioversion: risks due to unfamiliarity and recommendations

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World Journal of Emergency medicine 2024年第1期15卷 64-66页

作者： Hansol Chung Department of Emergency medicine Yeungnam University College of MedicineDaegu 42415Republic of Korea

During cardiopulmonary resuscitation(CPR),defibrillation,or cardioversion,the use of self-adhesive pads instead of conventional paddles has gradually become common.In particular,it was recommended during the COVID-19 pandemic,as it allows defibrillation or cardioversion to be performed without close contact between the rescuer and patient.[1,2]Self-adhesive pads can minimize the downtime of chest compressions before and after defibrillation and protect the patient from electric arc formation,skin burns,and fi re.Once the pads are attached,electrocardiographic rhythm analysis,defibrillation,synchronous cardioversion,and cardiovascular support are all possible.Unlike paddles,self-adhesive pads can save time because the application of conductive jelly,repeated positioning,and application of 10-12 kg of pressure on the chest are not needed.The European Resuscitation Council(ERC)Guidelines 2021 state that the use of self-adhesive pads is recommended in advanced cardiovascular life support(ACLS).[3]Nevertheless,some medical staff still tend to prefer the use of conventional paddles instead of self-adhesive pads in hospitals.

关键词： attached cardio conductive

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Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models

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Neural Regeneration Research 2024年第8期19卷 1728-1733页

作者： Sanika M.Joshi Theresa Currier Thomas Nafisa M.Jadavji college of Osteopathic medicine Midwestern UniversityGlendaleCAUSA Department of Biomedical Sciences Midwestern UniversityGlendaleCAUSA Department of Child Health College of Medicine–PhoenixUniversity of ArizonaPhoenixAZUSA college of Veterinary medicine Midwestern UniversityGlendaleCAUSA Department of Neuroscience Carleton UniversityOttawaCanada

Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.

关键词： folic acid nicotinamide one-carbon metabolism riboflavin traumatic brain injury vitamin B12 vitamin B2 vitamin B3

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