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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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Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people

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Journal of Genetics and Genomics 2024年第5期51卷 517-530页

作者： Yuntao Sun Mengge Wang Qiuxia Sun Yan Liu Shuhan Duan Zhiyong Wang Yunyu Zhou Jun Zhong Yuguo Huang Xinyu Huang Qingxin Yang Xiangping Li Haoran Su Yan Cai Xiucheng Jiang Jing Chen Jiangwei Yan Shengjie Nie Liping Hu Junbao Yang Renkuan Tang Chuan-Chao Wang Chao Liu Xiaohui Deng Libing Yun Guanglin He West China School of Basic Science&forensic medicine Sichuan UniversityChengduSichuan 610041China Institute of Rare Diseases West China Hospital of Sichuan UniversitySichuan UniversityChengduSichuan 610000China Center for Archaeological Science Sichuan UniversityChengduSichuan 610000China Faculty of forensic medicine Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510275China Guangzhou forensic Science Institute GuangzhouGuangdong 510055China Department of forensic medicine College of Basic MedicineChongqing Medical UniversityChongqing 400331China School of Clinical Medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of Basic Medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of forensic medicine Kunming Medical UniversityKunmingYunnan 650500China School of Stomatology North Sichuan Medical CollegeNanchongSichuan 637100China Department of Medical Laboratory North Sichuan Medical CollegeNanchongSichuan 637007China School of Life Sciences Xiamen UniversityXiamenFujian 361005China Anti-Drug Technology Center of Guangdong Province GuangzhouGuangdong 510230China School of forensic medicine Shanxi Medical UniversityJinzhongShanxi030600China

Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period.However,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain unknown.Here,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking people.We identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis.We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers.Adaptative signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in Tibetan.TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

关键词： Tibeto-Burman people Geneticprofile Natural selection Geneticdiversity Biological adaptation

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Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

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Neural Regeneration Research 2025年第4期20卷 1015-1030页

作者： Ruoyu Huang Qiuyu Pang Lexin Zheng Jiaxi Lin Hanxi Li Lingbo Wan Tao Wang Department of forensic Science School of Basic Medicine and Biological SciencesSuzhou Medicine College of Soochow UniversitySuzhouJiangsu ProvinceChina

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

关键词： cell death cholesterol metabolism intracerebral hemorrhage myelination therapeutic target

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Inhibiting the expression of hepatocyte nuclear factor 4 alpha attenuates lipopolysaccharide/ D-galactosamine-induced fulminant hepatic failure in mice

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Hepatobiliary & Pancreatic Diseases International 2012年第6期11卷 624-629页

作者： En-Qiang Chen, Dao-Yin Gong, Xiao-Hua Leng, Lang Bai, Cong Liu, Li-Chun Wang , Hong Tang Center for Infectious Diseases, West China Hospital and State Key Laboratory of Biotherapy ,Department of forensic Pathology, college of Basic medicine and forensic medicine , Sichuan University, Chengdu 610041, China Center for Infectious Diseases West China Hospital and State Key Laboratory of Biotherapy Sichuan University Chengdu 610041 China Department of forensic Pathology College of Basic Medicine and Forensic Medicine Sichuan University Chengdu 610041 China

BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed. RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF. CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.

关键词： hepatocyte nuclear factor 4α short-hairpin RNA fulminant hepatic failure lipopolysaccharide D-galactosamine

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Demonstration of safety characteristics and effects on gut microbiota of Lactobacillus gasseri HMV18

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Food Science and Human Wellness 2024年第2期13卷 611-620页

作者： Xianxian Jia Miaomiao Jia Xiang Gao Xiang Li Mengyuan Wang Shengqiang Du Rui Huang Xiaotong Li Jun Zhang Shujin Li Chunling Ma Yan Zhang Bin Cong Department of Pathogen Biology Institute of basic MedicineHebei Medical UniversityShijiazhuang 050017China Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology Chinese Academy of Medical SciencesShijiazhuang 050017China Institute of Basic medicine Hebei Medical UniversityShijiazhuang 050017China college of forensic medicine Hebei Key Laboratory of Forensic MedicineCollaborative Innovation Center of Forensic Medical Molecular IdentificationHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety Key Laboratory Hebei Food Inspection and Research InstituteShijiazhuang 050227China

Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.

关键词： Probiotics Lactobacillus gasseri Safety assessment Gut microbiota

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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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An Autopsy and Histopathology-based Study to Ascertain the Cause of Death of Brought Dead Cases

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Journal of forensic Science and medicine 2024年第1期10卷 28-33页

作者： Chandan Bandyopadhyay Prabir Chandra Paul Prabhas Chandra Chakraborty Department of forensic and State medicine Medical CollegeKolkataWest BengalIndia Department of Pathology Jagannath Gupta Institute of Medical Science and HospitalKolkataWest BengalIndia Department of forensic medicine and Toxicology NRS Medical College and HospitalKolkataand M.G.M Medical College and L S.K HospitalKishanganjBiharIndia

Background and Objectives:The cases of apparent natural deaths are encountered in the hospital casualties who are noted dead at the time of the first medical attention and as such are labeled as“Brought Dead.”These include the cases of sudden death,unexplained death,and unattended death.The cause of such deaths is reported in the literature to emanate principally from the cardiovascular system,though there are some documented geographical,racial,and other variations.In the present study,we endeavored to detect the cause of such natural deaths in terms of the disease and the organ system involved,in the deceased individuals of the contemporary Bengali population,with cases due to obvious unnatural causes being excluded.Materials and Methods:An observational,cross-sectional study with 105(n=105,male:89,female:16)study subjects of age group of 20-80 years,selected by systemic random sampling,from the brought dead subjects coming to the mortuary of the NRS Medical college and Hospital for medicolegal autopsy from April 2011 to March 2012,excluding cases having a history of the obvious unnatural event.Organ system-wise gross examination was done,followed by tissue sampling for histopathological examination.The case-wise findings were tabulated and analyzed for descriptive statistics using SPSS software.Results:In the present study,89 cases were male(84.8%)and 16 cases were female(15.2%),which reflects a male:female ratio of 5.56:1.The dead bodies are mostly recovered from the footpaths(47 cases,44%).Sixty-four(61%)cases are of known identity.In 54 cases out of 105(51.4%),morbid pathology is detected in the respiratory system(RS),lobar pneumonia,and cavitary pulmonary tuberculosis being the most frequent disease entity,in both genders.Fifty-one years-sixty-five years is found to be the most commonly affected age group,in both genders.Interpretation and Conclusions:The present study shows that the most common organ system involved in brought dead cases is the RS,which is supported by a few Indian studies.

关键词： Autopsy brought dead cause of death histopathology

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Investigation of the feasibility of NRAV as a biomarker for hepatocellular carcinoma

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Oncology Research 2024年第4期32卷 717-726页

作者： JUN LIU WENLI LI RUYUE LU JIAQING XU CHUNHUI JIANG JUNLIN DUAN LINGZHI ZHANG GUANFU WANG JIAXI CHEN Department of Clinical Laboratory Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical UniversityLinhaiChina Key Laboratory of System medicine and Precision Diagnosis and Treatment of Taizhou TaizhouChina Department of Clinical Laboratory Dongguan Hospital of Traditional Chinese MedicineDongguanChina School of Basic Medical Sciences forensic medicine Hangzhou Medical CollegeHangzhouChina

The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.

关键词： NRAV Hepatocellular carcinoma Prognosis Biomarker Pan-cancer

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