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Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

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Neural Regeneration Research 2024年第9期19卷 2041-2049页

作者： Zhihua Wang Wu Zhou Zhixiong Zhang Lulu Zhang Meihua Li Department of Neurosurgery The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Postdoctoral Innovation Practice Base The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Department of Nephrology Nanchang People’s Hospital Affiliated to Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury *** oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox *** is a classic drug used to treat type 2 diabetes that can inhibit *** studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 ***,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord *** test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord ***,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell *** intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord ***,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord *** together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

关键词： acyl-CoA synthetase long-chain family member 4 ferroptosis glutathione peroxidase 4 heme oxygenase-1 inflammation iron lipid peroxidation metformin neuroprotection spinal cord injury

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Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

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Oncology Research 2024年第5期32卷 899-910页

作者： YIWEN ZHU LIU YANG YING YU YING XIONG PING XIAO XIAO FU XIN LUO Department of Rehabilitation Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330006China Department of General Practice The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal *** there is no permanent therapy for this condition,it is necessary to develop a ***,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were *** experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were *** MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity *** reduced the Warburg effect and induced ferroptosis(FPT)in MG63 *** ferroptosis diminished HYSA’s anti-cancer activities in MG63 *** stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 ***-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°*** significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand ***,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 *** is a possible therapeutic option for OC or other cancers.

关键词： Hydroxysafflor yellow A Osteosarcoma HIF-1α FPT

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Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients

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Current Medical Science 2024年第4期44卷 771-788页

作者： Hong-xiang HUANG Pei-yuan ZHONG Ping LI Su-juan PENG Xin-jing DING Xiang-lian CAI Jin-hong CHEN Xie ZHUI Zhi-hui LUI Xing-yu TAO Yang-yang LIU Li CHEN Department of Oncology The First Affiliated Hospital of Nanchang UniversityNanchang330006China Jiangxi Institute of Respiratory Disease The First Affiliated Hospital of Nanchang UniversityNanchang330006China Department of Oncology Jiangxi Provincial People’s HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchang330006China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Nanchang UniversityNanchang330006China

Objective The activities and products of carbohydrate metabolism are involved in key processes of ***,its relationship with hepatocellular carcinoma(HCC)is *** The cancer genome atlas(TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public *** expressed genes(DEGs)between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes(CRGs)to obtain differentially expressed CRGs(DE-CRGs).Then,univariate Cox and least absolute shrinkage and selection operator(LASSO)analyses were applied to identify risk model genes,and HCC samples were divided into high/low-risk groups according to the median risk ***,gene set enrichment analysis(GSEA)was performed on the risk model *** sensitivity of the risk model to immunotherapy and chemotherapy was also *** A total of 8 risk model genes,namely,G6PD,PFKFB4,ACAT1,ALDH2,ACYP1,OGDHL,ACADS,and TKTL1,were ***,the risk score,cancer status,age,and pathologic T stage were strongly associated with the prognosis of HCC *** the stromal score and immune score had significant negative/positive correlations with the risk score,reflecting the important role of the risk model in immunotherapy ***,the stromal and immune scores had significant negative/positive correlations with risk scores,reflecting the important role of the risk model in immunotherapy ***,we found that high-/low-risk patients were more sensitive to 102 drugs,suggesting that the risk model exhibited sensitivity to chemotherapy *** results of the experiments in HCC tissue samples validated the expression of the risk model *** Through bioinformatic analysis,we constructed a carbohydrate metabolism-related risk model for HCC,contributing to the prognosis prediction and treatment of HCC patients.

关键词： hepatocellular carcinoma carbohydrate metabolism the cancer genome atlas bioinformatics

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Blueberry anthocyanins extract attenuates oxidative stress and angiogenesis on an in vitro high glucose-induced retinopathy model through the miR-33/GLCCI1 axis

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BIOCELL 2024年第8期48卷 1275-1284页

作者： WENBIN LUO YULING ZOU HONGXI WU ZHONGYI YANG ZHIPENG YOU Department of Ophthalmology The Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang330000China Department of Ophthalmology in Ocular Fundus Diseases Affiliated Eye Hospital of Nanchang UniversityNanchang330000China Department of Ophthalmic Treatment of Refractive Errors Affiliated Eye Hospital of Nanchang UniversityNanchang330000China

Background:Diabetes retinopathy(DR)is a complication of diabetes that affects patients’*** studies have found blueberry anthocyanins extract(BAE)can inhibit the progression of DR,but its mechanism is not completely ***:To study the role of BAE in diabetes retinopathy,we treated human retinal endothelial cells(HRCECs)with 30 mM high glucose to simulate the microenvironment of diabetes retinopathy and used BAE to intervene the in vitro high glucose-induced retinopathy *** cell viability and apoptosis rates were examined by Cell Counting Kit 8(CCK-8)assay and flow cytometry *** binding sites between miR-33 and glucocorticoid-induced transcript 1(GLCCI1)were assessed by luciferase reporter *** neovascularization and oxidative stress contribute to diabetic *** tubule formation assay was applied to detect the retinal *** oxidative stress in the HRCECs was manifested by the reactive oxygen species(ROS)level,the malondialdehyde(MDA)level,and the superoxide dismutase(SOD)***:Compared with HRCECs cells cultured under normal conditions,high glucose(HG)can induce oxidative stress in HRCRCs,specifically manifested in the increase of ROS and MDA levels,and the decrease of SOD *** relieved the tubule formation in n the *** also relieved the ROS and MDA levels and increased the SOD *** reporter assay revealed that GLCCI1 is a target molecule downstream of *** HRCEC,BAE significantly inhibited the expression of miR-33 induced by ***-33 mimic inhibited the BAE’s effects on oxidative stress and angiogenesis in an in vitro high glucose-induced retinopathy ***:BAE alleviated the oxidative stress and microangiogenesis of HRCEC by regulating the miR-33/GLCCI1 axis.

关键词： Blueberry anthocyanins extract Diabetic retinopathy Oxidative stress Retinal neovascularization miR-33 CLCCI1

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A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

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Current Medical Science 2024年第3期44卷 485-493页

作者： Xia-hui HUANG Tian-xiang CHEN Hong-liang LIU Ming-wen HUANG Department of General Surgery The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the *** lesions have been recognized as one of the three major precancerous lesions in the biliary tract since *** 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 *** are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and *** a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 *** histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant *** to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging *** resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

关键词： intraductal papillary neoplasm of the bile duct subclassification neoplasms precancerous tissue prognosis

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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu Medical College of nanchang university Department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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Identification of TP53 mutation-associated prognostic genes and investigation of the immune cell infiltration in patients with hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 520-523页

作者： Qijun Yang Lianke Gao Yuhan Xu Gaoquan Cao Yingcheng He Wenyige Zhang Xue Zhang Chengfeng Wu Kaili Liao Xiaozhong Wang Department of Clinical Laboratory The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Queen Mary College of nanchang university NanchangJiangxi 330031China Advanced Manufacturing College of nanchang university NanchangJiangxi 330031China The Forth Clinical School of nanchang university The South Road of Bayi SquareNanchangJiangxi 330031China Department of Vascular Surgery The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Primary liver cancer,which is mainly composed of hepatocellular carcinoma(HcC),is the sixth most common type of cancer worldwide and the thirdmost common cause of cancer mortality.1 The total number of mutations present in tumor specimens is called tumor mutation burden(TMB)and it is an emerging biomarker of immunotherapy response.2 TMB can predict clinical responses to immunotherapy such as ICl(immune checkpoint inhibitor)treatments and higher TMB is related to better survival.3 TP53,a gene encoding a tumor suppressor protein that triggers apoptosis and cell cycle arrest,is one of the most prevalent mutations in 25%-30%of HCC patients.4 Research shows that TP53 mutations in HCC patients are associated with advanced tumor grade and poor prognosis.5 To identify the TP53 mutation-related genes which can predict HCC patients'prognosis and explore the immune cell infiltration,we constructed a risk model based on six TP53 mutation-related genes which can accurately predict patients'***,six immune cells with a similar expression pattern were identified in The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)databases.

关键词： TP53 patients hepatocellular

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IGF2BPs as novel m^(6)A readers:Diverse roles in regulating cancer cell biological functions,hypoxia adaptation,metabolism,and immunosuppressive tumor microenvironment

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Genes & Diseases 2024年第2期11卷 890-920页

作者： Meiqi Duan Haiyang Liu Shasha Xu Zhi Yang Fusheng Zhang Guang Wang Yutian Wang Shan Zhao Xiaofeng Jiang Department of General Surgery The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning 110032China Department of Gastroendoscopy The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning 110032China Department of Rheumatology and Immunology The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110002China

m^(6)A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological ***-like growth factor 2 mRNA-binding proteins(IGF2BP)are newly identified m^(6)A‘readers’.They belong to a family of RNA-binding proteins,which bind to the m^(6)A sites on different RNA sequences and stabilize them to promote cancer *** this review,we summarize the mechanisms by which different upstream factors regulate IGF2BP in *** current literature analyzed here reveals that the IGF2BP family proteins promote cancer cell proliferation,survival,and chemoresistance,inhibit apoptosis,and are also associated with cancer glycolysis,angiogenesis,and the immune response in the tumor ***,with the discovery of their role as‘readers’of m^(6)A and the characteristic re-expression of IGF2BPs in cancers,it is important to elucidate their mechanism of action in the immunosuppressive tumor *** also describe in detail the regulatory and interaction network of the IGF2BP family in downstream target RNAs and discuss their potential clinical applications as diagnostic and prognostic markers,as well as recent advances in IGF2BP biology and associated therapeutic value.

关键词： Cancer IGF2BP Immunosuppressive TME m^(6)A Molecular mechanism Therapy

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Alcohol drinking triggered decrease of oxidative balance score is associated with high all-cause and cardiovascular mortality in hypertensive individuals:findings from NHANES 1999–2014

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Journal of Geriatric Cardiology 2024年第8期21卷 779-790页

作者： Yu-Jun ZHANG Jing-Jing SONG Jian-Hao ZHAN Chu-Lin ZHOU Ao LI Mao-Qi WANG Ben-Jie LI Cong-Cong DING Yi-Wei ZHANG Zi-Heng TAN Zai-Hua CHENG Xiao HUANG Department of Cardiology the Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangChina Huankui Academy Nanchang UniversityNanchangChina School of Ophthalmology and Optometry of nanchang university NanchangChina The Second Clinical Medical College Nanchang UniversityNanchangChina Queen Mary School Nanchang UniversityNanchangChina The First Clinical Medical College Nanchang UniversityNanchangChina Department of Cardiovascular Medicine Huzhou First People’s HospitalZhejiangChina

BACKGROUND Oxidative stress is closely associated with hypertensive *** oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle *** objective of this study was to investigate the association between OBS and mortality in hypertensive *** This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)*** models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of *** Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity *** after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never *** In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular *** hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.

关键词： high finding Alcohol

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OSMR is a potential driver of inflammation in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第11期19卷 2513-2521页

作者： Wenzhi Chen Shishi Jiang Shu Li Cheng Li Renshi Xu Department of Neurology Jiangxi Provincial People’s HospitalXiangya Hospital Jiangxi Hospital of Central South UniversityThe Clinical College of Nanchang Medical CollegeThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly ***,inflammation is known to play an important role in the development of this *** identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral ***,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on SJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral *** results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory ***,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral *** findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.

关键词： amyotrophic lateral sclerosis driver neuroinflammation OSMR C9ORF72 neurodegenerative disease pathogenesis oxidative stress protein misfolding mitochondrial dysfunction

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