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Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration Research 2024年第2期19卷 405-406页

作者： Fabio Coppedè department of translational Research and of New surgical and medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

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World Journal of Gastroenterology 2024年第17期30卷 2294-2297页

作者： Fabiola Di Dato Raffaele Iorio department of translational medical science Section of PediatricsUniversity of Naples Federico IINaples 80131Italy

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular *** the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis ***,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the *** are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment *** editorial addresses key questions about the topic and whether indications for treatment should be expanded.

关键词： Hepatitis B virus Interferon Nucleos(t)ide analogues Functional cure Children

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma:A Western perspective

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World Journal of Gastroenterology 2024年第31期30卷 3635-3639页

作者： Marco Biolato Maurizio Pompili department of medical and surgical sciences CEMAD Digestive Disease CenterFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy department of translational medicine and Surgery Catholic University of Sacred HeartRome 00168LazioItaly

Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial *** strategies have been evaluated to reduce the incidence of PES,but no standard prevention guidelines currently *** a single-center,placebo-controlled trial,Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES(from 80%to 6%),of post-procedural liver decompensation(from 14%to 0%),and a shorter hospital stay(4 days vs 6 days),alongside an acceptable safety *** results of this study raise several controversial points regarding their applicability in the Western *** the West,there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis,so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone ***,in the West,there is a preferred use of drug-eluting beads loaded with doxorubicin,which are associated with a lower incidence of PES.A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

关键词： Chemotherapeutic drugs Lipiodol Post-embolization syndrome Prevention Prophylaxis

Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li department of Rehabilitation medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study

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World Journal of Transplantation 2024年第2期14卷 99-106页

作者： Marco Biolato Luca Miele Giuseppe Marrone Claudia Tarli Antonio Liguori Rosaria Calia Giovanni Addolorato Salvatore Agnes Antonio Gasbarrini Maurizio Pompili Antonio Grieco department of medical and surgical sciences CEMADFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy department of translational medicine and Surgery Catholic University of Sacred HeartRome 00168Italy

BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation *** To assess the ineligibility rate for liver transplantation and its *** A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation *** predictors for listing were evaluated using multivariable logistic *** In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year *** most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole *** hundred and five motivations for ineligibility were *** most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)*** multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of *** A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of *** referral from another hospital was taken as a strong predictor of non-listing.

关键词： Controindication Eligibility Evaluation Referral Personalized medicine

Optimizing prediction models for pancreatic fistula after pancreatectomy:Current status and future perspectives

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World Journal of Gastroenterology 2024年第10期30卷 1329-1345页

作者： Feng Yang John A Windsor De-Liang Fu department of Pancreatic Surgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China surgical and translational Research Centre Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1142New Zealand

Postoperative pancreatic fistula(POPF)is a frequent complication after pancre-atectomy,leading to increased morbidity and *** prediction models for POPF has emerged as a critical focus in surgical *** over sixty models following pancreaticoduodenectomy,predominantly reliant on a variety of clinical,surgical,and radiological parameters,have been documented,their predictive accuracy remains suboptimal in external validation and across diverse *** models after distal pancreatectomy continue to be pro-gressively reported,their external validation is eagerly ***,POPF prediction after central pancreatectomy is in its nascent stage,warranting urgent need for further development and *** potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm ***,there is potential for the development of personalized prediction models based on patient-or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of *** the future,prospective multicenter studies and the integration of novel imaging technologies,such as artificial intelligence-based radiomics,may further refine predictive *** these issues is anticipated to revolutionize risk stratification,clinical decision-making,and postoperative management in patients undergoing pancre-atectomy.

关键词： Pancreatic fistula Pancreaticoduodenectomy Distal pancreatectomy Central pancreatectomy Prediction model Machine learning Artificial intelligence

Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China Bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang Fei Fei Zhou Fei Xia Li department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National translational science Center for Molecular medicine and department of Cell Biology Fourth Military Medical UniversityXi'an 710000China department of Neurosurgery The Central Hospital of BaojiBaoji 721000China department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude *** plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains *** we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain *** autophagic agonist rapamycin only promotes the initiation of *** proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic *** of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with ***,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH *** results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1291-1298页

作者： Qi Jia Jin Li Xiaofeng Guo Yi Li You Wu Yuliang Peng Zongping Fang Xijing Zhang department of Anesthesiology and Perioperative medicine and department of Intensive Care Unit Xijing Hospital The Fourth Military Medical University department of Critical Care medicine translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins. Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis, while providing nutrients and support for cell survival. Chaperone-mediated autophagy activity can be detected in almost all cells, including neurons. Owing to the extreme sensitivity of neurons to their environmental changes, maintaining neuronal homeostasis is critical for neuronal growth and survival. Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases. It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction. Under certain conditions, regulation of chaperone-mediated autophagy activity attenuates neurotoxicity. In this paper, we review the changes in chaperone-mediated autophagy in neurodegenerative diseases, brain injury, glioma, and autoimmune diseases. We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

关键词： chaperone-mediated autophagy neurodegenerative disease neuronal homeostasis neuroprotection