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Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Neural Regeneration Research 2024年第2期19卷 316-323页

作者： Yiyang Chen Wenxuan Tang Xinqi Huang Yumei An Jiawen Li Shengye Yuan Haiyan Shan Mingyang Zhang Institute of forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina Shanghai Key Lab of forensic Medicine Key Lab of Forensic ScienceMinistry of Justice(Academy of Forensic Science)ShanghaiChina department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

关键词： intracerebral hemorrhage mitochondrial dysfunction mitophagy neuroinflammation neuroprotection reactive oxygen species secondary brain injury therapeutic target

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The role of snapin in regulation of brain homeostasis

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Neural Regeneration Research 2024年第8期19卷 1696-1701页

作者： Jiawen Li Xinqi Huang Yumei An Xueshi Chen Yiyang Chen Mingyuan Xu Haiyan Shan Mingyang Zhang Shanghai Key Lab of forensic Medicine Key Lab of Forensic ScienceMinistry of JusticeChina(Academy of Forensic Science)ShanghaiChina Institute of forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

关键词： brain homeostasis diabetes neurological diseases snapin traumatic brain injury vesicle fusion

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Major depressive disorder:hypothesis,mechanism,prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第3期9卷 913-944页

作者： Lulu Cui Shu Li Siman Wang Xiafang Wu Yingyu Liu Weiyang Yu Yijun Wang Yong Tang Maosheng Xia Baoman Li department of forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangChina Liaoning Province Key Laboratory of forensic Bioevidence Sciences ShenyangChina China Medical University Centre of forensic Investigation ShenyangChina International Joint Research Centre on Purinergic Signalling/Key Laboratory of Acupuncture for Senile Disease(Chengdu University of TCM) Ministry of Education/School of Health and RehabilitationChengdu University of Traditional Chinese Medicine/Acupuncture and Chronobiology Key Laboratory of Sichuan ProvinceChengduChina department of Orthopaedics The First HospitalChina Medical UniversityShenyangChina

Worldwide,the incidence of major depressive disorder(MDD)is increasing annually,resulting in greater economic and social burdens.Moreover,the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear,and additional diagnostic and therapeutic strategies for MDD still are needed.The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis,hypothalamicpituitary-adrenal(HPA)axis hypothesis,cytokine hypothesis,neuroplasticity hypothesis and systemic influence hypothesis,but these hypothesis cannot completely explain the pathological mechanism of MDD.Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD,thus in recent years,great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies,further revealing the disease features of MDD.Furthermore,some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention,some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms.In this work,we comprehensively summarize the latest research on the pathogenesis and diagnosis of MDD,preventive approaches and therapeutic medicines,as well as the related clinical trials.

关键词： prevention acupuncture hypothesis

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Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy

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Science China(Life Sciences) 2024年第6期67卷 1155-1169页

作者： Shuai Yuan Xudong Zhang Jiabing Zhan Rong Xie Jiahui Fan Beibei Dai Yanru Zhao Zhongwei Yin Qian Liu Dao Wen Wang Huaping Li Chen Chen Division of Cardiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of genetics and Molecular Mechanisms of Cardiological Disorders Wuhan 430030China department of forensic Medicine Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in DCM.Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts.Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in vivo.Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to myofibroblasts.CFIRL knockdown attenuated these effects.Mechanistically,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate IL-6transcription.IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL knockdown.These findings uncover the critical role of CFIRL,a fibroblast-associated lnc RNA,in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes.CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.

关键词： lncRNA fibroblast fibrosis dilated cardiomyopathy heart failure

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Preimplantation genetic testing for embryos predisposed to hereditary cancer:Possibilities and challenges

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Cancer Pathogenesis and Therapy 2024年第1期2卷 1-14页

作者： Mohammed H.Albujja Maher Al-Ghedan Lakshmidevi Dakshnamoorthy Josep Pla Victori department of forensic Sciences Naif Arab University for Security SciencesRiyadh 11452Saudi Arabia genetics Laboratory Thuriah Medical CenterRiyadh 11523Saudi Arabia department of Genetic Counselling VI-RMA GlobalValencia 46004Spain

Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus.Originally used for early onset monogenic conditions,PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology,assisted reproductive techniques(ARTs),and in vitro fertilization(IVF).This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test,with a particular focus on the current challenges related to laws,ethics,counseling,and technology.Additionally,this review predicts the future potential applications of this method.Although PGT may be utilized to predict and prevent hereditary cancer,each case should be comprehensively evaluated.The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes,and non-pathogenic phenotypes must be carefully evaluated.Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning.PGT may be the preferred treatment for hereditary cancer cases;however,such cases require careful case-by-case evaluations.Therefore,this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.

关键词： Preimplantation genetic testing Hereditary cancer Late-onset diseases Ethics Legal restrictions

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Exploring the molecular landscape of NNK-induced transformation:A comprehensive genome-wide CRISPR/Cas9 screening

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Genes & Diseases 2024年第4期11卷 42-44页

作者： Trang Dinh Mira Rahm Zhenghe Wang Christopher McFarland Athar Khalil department of genetics and Genome Sciences Case WesternReserve UniversityClevelandOH44106USA

Lung cancer is the leading cause of cancer-related deaths worldwide,with an estimated 1.8 million deaths in 2020 alone.1 While several risk factors are associated with lung cancer,smoking remains the most significant environmental cause of the disease.1 One of the most potent carcinogens in tobacco smoke is 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone(NNK),which is produced from nicotine through a series of metabolic reactions.

关键词： CRISPR/Cas9 NNK lung

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Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

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World Journal of Diabetes 2024年第5期15卷 814-817页

作者： Ashraf Al Madhoun department of genetics and Bioinformatics Dasman Diabetes InstituteDasman 15400Kuwait

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

关键词： Glucokinase regulatory protein rs780094 Type 2 diabetes mellitus Dyslipidemia Non-alcoholic fatty liver disease Nephropathy

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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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Medicinal Effects, Phytochemistry,Pharmacology of Euphorbia prostrata and Promising MolecularMechanisms

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Chinese Journal of Integrative Medicine 2024年第2期30卷 181-192页

作者： Nirmala Kumari Yadav Rakesh Yadav department of Pharmacy Banasthali VidyapithBanasthali(304022)RajasthanIndia department of Pharmaceutical Sciences Indira Gandhi UniversityMeerpurRewari(122502)HaryanaIndia National forensic Sciences University Tripura CampusAgartala(799001)TripuraIndia

Euphorbiaceae is a large family of dicotyledonous angiosperms with diverse genera including Euphorbia prostrata(E.prostrata).Current research has provided scientific evidence for traditional uses of E.prostrata against diverse pathological conditions such as anti-hemorrhoidal,anti-inflammatory,analgesic,wound healing,antioxidant,antibacterial,leishmanicidal,antitumor activity,and so on.The phytochemical screening has revealed the presence of glycosides,phytosterols,flavonoids,polyphenols,tannins,and anthraquinones with chemical structures elucidation of their respective compounds.The uniqueness of such multifactorial compounds present in this species endorses it as the potent therapeutic or prophylactic choice for several fatal diseases.Although ethnomedical applications served as a significant citation for pharmacology,the molecular mechanism has not been reviewed yet.The present paper provides a comprehensive review of research outcomes,pharmacology,toxicology,and molecular signaling of phytochemicals of E.prostrata species as a reference for relevant researchers.The study of bioactive compounds in crude extracts and fractions,the demonstration of primary mechanisms of pharmacology,along with the addition of toxicity,and clinical trials,should be conceded in depth.This review underlines the E.prostrata species that can be a promising phytomedicine since we are committed to excavating more intensely into their pharmacological role.

关键词： Euphorbia prostrata Euphorbiaceae phytochemicals ethnomedical applications toxicology molecularmechanism

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Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of Neurology of the Second Afliated Hospital and department of Human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of Physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of Human Reproduction and Developmental genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

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