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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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Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

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Oncology Research 2024年第2期32卷 353-360页

作者： ZHI ZHANG XIAOSONG LI YING ZHANG HAO ZHU ZHENGUO QIAO YANG LU XIUWEI MI HUIHUA CAO GENHAI SHEN SONGBING HE department of General Surgery Suzhou Ninth People’s HospitalSuzhou Ninth Hospital Affiliated to Soochow UniversitySuzhouChina Medical College of Nantong university NantongChina department of Gastroenterology Suzhou Ninth People’s HospitalSuzhou Ninth Hospital Affiliated to Soochow UniversitySuzhouChina department of General Surgery The First Affiliated Hospital of Soochow UniversitySuzhouChina department of Oncological Surgery Kunshan Traditional Hospital Affiliated to Nanjing University of Chinese MedicineKunshanChina

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality *** in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome *** this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain ***,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in *** findings showed a reduced AIM2 expression in most CRC cell *** of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell *** research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and ***,our achievements distinctly underscored AIM2’s antitumor role in ***2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

关键词： Absent in melanoma 2 Proliferation Migration Apoptosis P38MAPK Colorectal cancer

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Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

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Neural Regeneration Research 2024年第4期19卷 825-832页

作者： Jiatong Zhang Qi Zhu Jie Wang Zheng Peng Zong Zhuang Chunhua Hang Wei Li department of Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University department of Neurosurgery Nanjing Drum Tower HospitalClinical College of Nanjing Medical University

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood *** are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial *** mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging *** response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological *** interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid *** review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control *** also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

关键词： mitochondrial biogenesis mitochondrial dynamics mitochondrial dysfunction mitochondrial fission and fusion mitochondrial quality control mitophagy subarachnoid hemorrhage

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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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High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu department of Rehabilitation Medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction *** magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem ***,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic ***-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ***,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and *** effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem ***,we validated the effect of repetitive TMS on AKT *** found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin *** findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling *** study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro *** results provide a stro ng scientific foundation for the clinical application of repetitive ***,repetitive TMS treatment may not only be an efficient an

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer

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Nano Research 2024年第8期17卷 7504-7512页

作者： Meijin Yang Zhiying Tang Xiaoying Li Yanzi Yu Lizhen He Tianfeng Chen College of Chemistry and Materials Science Department of Oncology of The First Affiliated HospitalJinan UniversityGuangzhou 510632China

Bone metastasis along with osteolysis is a common complication of advanced breast cancer,which directly destroys bone function and becomes one of the major causes of cancer-related *** is crucial to develop a new strategy to achieve effective cancer therapy and inhibition of osteolytic bone *** ruthenium(Ru)complexes exhibit therapeutic potential in cancer ***,the clinical applications of Ru complexes were limited by poor bioavailability,lacking targeting,nonspecific ***,in this study,engineering of cell membrane biomimetic modification was used to construct a highly biocompatible nanoplatform with carrying Ru metal complex of RuPOP and Se nanoparticles(SeNPs).Strikingly,the obtained RPSR nanoparticles can efficiently inhibit the proliferation,invasion and migration of breast cancer cells(MDA-MB-231 cells)in *** importantly,RPSR nanoparticles can induce cycle arrest,apoptosis by generating excessive intracellular(reactive oxygen species,ROS)to disrupt the normal redox balance and induce DNA damage in tumor ***,RPSR nanoparticles can also reshape bone microenvironment by regulating selenoproteins to inhibit osteoclasts and avoid osteolytic bone metastasis induced by tumor *** together,this study not only provides an effective cell membrane biomimetic strategy to enhance the shortcomings of metal complexes,but also demonstrates potential clinical significance for the combined treatment of anti-cancer and bone metastasis inhibition.

关键词： cell membrane nanoparticles biomimetic modification ruthenium complexes selenium nanoparticles tumor bone metastasis

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Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 273-286页

作者： Di Pan Hao-Nan Liu Peng-Fei Qu Xiao Ma Lu-Yao Ma Xiao-Xiao Chen Yu-Qin Wang Xiao-Bing Qin Zheng-Xiang Han department of Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina department of Gastroenterology The Second Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina department of General Surgery The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human *** to challenges in early diagnosis,most patients lose the opportunity for radical treatment when ***,recent advancements in cancer immunotherapy provide new directions for the treatment of *** instance,monoclonal antibodies against immune check-point inhibitors(ICIs)such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with ***,tumor cells can evade the immune system through various *** the rapid development of genetic engineering and molecular biology,various new immunotherapies have been used to treat HCC,including ICIs,chimeric antigen receptor T cells,engineered cytokines,and certain cancer *** review summarizes the current status,research progress,and future directions of different immunotherapy strategies in the treatment of HCC.

关键词： Hepatocellular carcinoma Immunotherapies Immune checkpoint inhibitor Clinical efficacy Adverse reactions

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Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 361-369页

作者： Zhong-Xing Shi Chang-Fu Li Li-Feng Zhao Zhong-Qi Sun Li-Ming Cui Yan-Jie Xin Dong-Qing Wang Tan-Rong Kang Hui-Jie Jiang department of Interventional Radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China department of Digestive Medicine Daqing Longnan HospitalDaqing 163453China department of Radiology Daqing Longnan HospitalDaqing 163453China department of Radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment *** study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient ***:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were *** tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were *** radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was *** predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration ***:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s *** were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment *** predicted treatment response also allowed for significant discrimination of Kaplan-Meier *** Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interva

关键词： Hepatocellular carcinoma Transarterial chemoembolization Radiomics Treatment response Prediction

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A deep learning model based on contrast-enhanced computed tomography for differential diagnosis of gallbladder carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 376-384页

作者： Fei Xiang Qing-Tao Meng Jing-Jing Deng Jie Wang Xiao-Yuan Liang Xing-Yu Liu Sheng Yan department of Hepatobiliary Pancreatic Surgery Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Radiology Affiliated Chuzhou First People’s HospitalAnhui Medical UniversityChuzhou 239000China

Background:Gallbladder carcinoma(GBC)is highly malignant,and its early diagnosis remains *** study aimed to develop a deep learning model based on contrast-enhanced computed tomography(CT)images to assist radiologists in identifying ***:We retrospectively enrolled 278 patients with gallbladder lesions(>10 mm)who underwent contrast-enhanced CT and cholecystectomy and divided them into the training(n=194)and validation(n=84)*** deep learning model was developed based on ResNet50 *** and clinical models were built based on support vector machine(SVM)*** comprehensively compared the performance of deep learning,radiomics,clinical models,and three ***:Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance,HHL firstorder kurtosis,and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC,and were selected for developing radiomics *** regression analysis revealed that age≥65 years[odds ratios(OR)=4.4,95%confidence interval(CI):2.1-9.1,P37 U/mL(OR=4.0,95%CI:1.6-10.0,P=0.003)were significant clinical risk factors of *** deep learning model achieved the area under the receiver operating characteristic curve(AUC)values of 0.864(95%CI:0.814-0.915)and 0.857(95%CI:0.773-0.942)in the training and validation datasets,which were comparable with radiomics,clinical models and three *** sensitivity of deep learning model was the highest both in the training[90%(95%CI:82%-96%)]and validation[85%(95%CI:68%-95%)]***:The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

关键词： Gallbladder carcinoma Computed tomography Deep learning Radiomics

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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong Li Wei Li Yanli Zhang Linping Xu Yongping Song department of Hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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