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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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ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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Nano Research 2024年第3期17卷 1772-1784页

作者： Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu Department of Orthopedics Orthopedic Laboratory of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China The affiliated Traditional Chinese Medicine hospital of Southwest medical university Luzhou 646699China Department of Orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China Department of Orthopedics Chongqing University Three Gorges HospitalChongqing 404000China Department of Geriatrics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025China Beijing Key Laboratory of Lignocellulosic Chemistry College of Material Science and TechnologyBeijing Forestry UniversityBeijing 100083China

Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high *** article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug *** can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS *** produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS *** the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of *** vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS *** in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS ***,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关键词： zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis

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New therapeutic target NCF1-directed multi-bioactive conjugate therapies prevent preterm birth and adverse pregnancy outcomes

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Science Bulletin 2024年第16期69卷 2604-2621页

作者： Juan Cheng Xiaoyan Jia Limei Yang Siqi Zhang Zhiyu Chen Qian Gui Ting Li Zedan Pu Hongbo Qi Jianxiang Zhang Chongqing Key Laboratory of Maternal and Fetal Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Women and Children’s hospital of Chongqing medical university Chongqing 401147China Department of Obstetrics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Pharmaceutics College of PharmacyThird Military Medical University(Army Medical University)Chongqing 400038China Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Yu-Yue Pathology Scientific Research Center Chongqing 400039China State Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University(Army Medical University)Chongqing 400038China

Preterm birth(PTB)is a leading cause of neonatal morbidity and mortality worldwide,yet the cellular and molecular mechanisms driving this condition remain undeciphered,thus limiting discovery of new ***-depth analyses of human and mouse tissues associated with PTB,in combination with cellular studies,indicated that aberrantly high-expressed neutrophil cytoplasmic factor(NCF)1 leads to oxidative distress,recruitment,and pro-inflammatory activation of neutrophils and macrophages,while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells(USMCs)as well as apoptosis of USMCs and amniotic epithelial cells,thereby causing *** to these new findings,we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin,a reactive oxygen species-responsive/scavenging component,and an anti-inflammatory *** bioengineered macromolecular conjugate can selfassemble into multi-bioactive nanoparticles(LPA NP).In a mouse model of PTB,LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes,by regulating NCF1-mediated oxidativeinflammatory cascades,i.e.,attenuating oxidative stress,inhibiting inflammatory cell activation,reducing local inflammation,and decreasing contraction/apoptosis of myometrial *** LPA NP into temperature-responsive,self-healing,and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery,by prolonging retention time,sustaining nanotherapy release,and increasing bioavailability in the placenta/***,both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice,with negligible side effects on the mother and offspring.

关键词： Preterm birth Neutrophil cytoplasmic factor Bioactive conjugate Nanotherapy Hydrogel therapy

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical Research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

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Current medical Science 2024年第2期44卷 406-418页

作者： Cheng-cheng ZHU Heng-liang SUN Teng-fei LONG Yuan-yuan LYU Jiang-li LIU Guan-tai NI Anhui medical university Hefei 230032China Department of Obstetrics and Gynecology The First Affiliated Hospital of Wannan Medical CollegeWuhu 241001China

Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s *** precise mechanism underlying the development of UCEC remains *** finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant *** study aimed to examine the involvement of ZNF554 in the development of ***:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot *** with stably overexpressed or knocked-down ZNF554 were established through lentivirus ***-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and *** iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle ***-PCR and Western blotting were conducted to examine relative mRNA and protein *** immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell *** expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in ***554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle *** contrast,a decrease in ZNF554 expression resulted in the opposite ***,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling ***,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and

关键词： zinc finger protein 554 endometrial carcinoma RNA binding motif 5 Wingless/β-catenin signaling pathway

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Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

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World Journal of Gastroenterology 2024年第14期30卷 2038-2058页

作者： Pan Zheng Xue-Yang Li Xiao-Yu Yang Huan Wang Ling Ding Cong He Jian-Hua Wan Hua-Jing Ke Nong-Hua Lu Nian-Shuang Li Yin Zhu Department of Gastroenterology Digestive Disease HospitalThe First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ *** the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal *** this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP *** To investigate the shared molecular changes underlying the development of AP across varying severity *** AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce ***,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)*** Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue *** with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS *** Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome *** significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal *** from the GEO database revealed that only MYD88 concurred in both mouse panc

关键词： Acute pancreatitis RNA-sequencing Experimental acute pancreatitis models Inflammatory Apoptosis TLR and NOD-like signaling pathways

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Click-hydrogel delivered aggregation-induced emissive nanovesicles for simultaneous remodeling and antibiosis of deep burn wounds

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Aggregate 2024年第1期5卷 244-256页

作者： Xu Chen Meijiao Zhao Qihu Xie Sitong Zhou Xiaoping Zhong Judun Zheng Ronghua Yang Xianjin Du Jinyu Xia Yuhui Liao Department of Infectious Diseases The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina Molecular Diagnosis and Treatment Center for Infectious Diseases Dermatology HospitalSouthern Medical UniversityGuangzhouChina Department of Burns and Plastic Surgery The Second Affiliated Hospital of Shantou University Medical CollegeShantouChina Department of Dermatology TheFirst People’s Hospital of FoshanFoshanChina Department of Burn and Plastic Surgery Guangzhou First People’s HospitalSouth China University of TechnologyGuangzhouChina Department of Critical Care Medicine Renmin Hospital of Wuhan UniversityWuhanChina

As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent *** this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry *** aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating *** addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on *** hydrogel could be injected to conform to the wound morphology while responding to the acidic *** vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen *** study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.

关键词： aggregation-induced emission burn wounds nanovesicles

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Single-Nucleus RNA Sequencing Reveals Cardiac Macrophage Landscape in Hypoplastic Left Heart Syndrome

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Congenital Heart Disease 2024年第2期19卷 233-246页

作者： Xiaozhuo Xu Yilin Huang Xu Han first Clinical medical college Affiliated Hospital of Nanjing University of Chinese MedicineNanjing210008China Department of Geriatrics Affiliated Hospital of Nanjing University of Chinese MedicineNanjing210029China

Background:Hypoplastic left heart syndrome(HLHS)is one of the most challenging congenital heart diseases in clinical *** cardiac tissues,resident macrophages fulfill critical functions in maintaining a stable cardiac state and have strong regenerative capacity and organ ***,the molecular mechanisms of macro-phages in HLHS remained ***:Single-nucleus RNA sequencing(snRNA-seq)data of HLHS and healthy control(donors)samples obtained from the Gene Expression Omnibus(GEO)database were normalized and clustered using the Seurat ***“FindMarkers”function was used to screen differentially expressed genes(DEGs)between the HLHS and donor groups and to analyze the functional enrichment of the set of genes of ***,cell-cell communication,pseudotime,and single-cell regulatory network inference and cluster-ing(SCENIC)analyses were used to study the mechanisms of macrophages in ***:Based on the snRNA-seq data of HLHS and donors,we identified a total of 9 cell clusters,among which the proportion of macrophages was significantly less in the HLHS group than in the control *** of macrophage subpopulations(Macrophages 1,2,and 3)showed that Macrophages 1 was mainly involved in nervous system development,angiogenesis,and apoptotic *** addition,analysis of communication between Macro-phages 1 and cardiomyocytes revealed that ligand-acceptor pairs such as GAS6/AXL,IL6,IGF1,THY1,and L1CAM were present only in the donor ***,pesudotime and SCENIC analyses demonstrated that FOXO3 and ELF2 played a critical role for Macrophages 1 to maintain cardiac function in patients with ***:Our study improved the current understanding of the molecular mechanisms of macrophage devel-opment in HLHS,showing that manipulating the regulatory role of macrophages in the heart can be a novel treat-ment for HLHS.

关键词： Hypoplastic left heart syndrome single-nucleus RNA sequencing macrophage cellular subpopulation transcription factor

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Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第5期30卷 449-457页

作者： XIE Shuang-ran MA Liang XU Xin-yu ZHOU Shu XIE Hui-miao XIE Chang-sheng The first Clinical medical college Zhejiang Chinese Medical UniversityHangzhou 310053China Department of medical Oncology Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical UniversityHangzhou 310007China Department of Dermatology the Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Famous Chinese Medicine Clinic the Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310005China Department of medical Oncology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China

Backgroup:Currently,aromatherapy is being increasingly utilized in clinical practice,particularly in managing the side effects associated with radiotherapy and ***,it remains to be established whether aromatherapy can effectively alleviate these ***:To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and ***:Seven databases were researched from inception until September 29,2023,including PubMed,Scopus,and Web of Science,Chinese National Knowledge Infrastructure,Wanfang database,China Biology Medicine disc and VIP Chinese medical Journal *** Manager version 5.3 was utilized for data *** Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the *** quality rating was assessed using the Grading of Recommendations Assessment,Development,and Evaluation(GRADE) approach through the GRADEpro GDT online ***:Nineteen studies involving 1,541 patients were *** can alleviate nausea [relative risk(RR)=0.64,95% confidence interval(CI):0.53 to 0.78,P<0.05,I^(2)=46%;standardized mean difference(SMD)=-0.86,95% CI:-1.21 to-0.51,P<0.05,I^(2)=64%] and vomiting(RR=0.54,95% CI:0.42 to 0.69,P<0.05,I^(2)=35%;SMD=-1.28,95% CI:-1.52 to-1.03,P<0.05,I^(2)=92%),improve sleep disorders [mean difference(MD)=-3.39,95% CI:-3.95 to-2.84,P<0.05,I^(2)=0%],relieve pain(SMD=-1.58,95% CI:-1.96 to-1.21,P<0.05,I^(2)=0%),mitigate fatigue(SMD=-1.28,95% CI:-2.44 to-0.11,P<0.05,I^(2)=93%) and enhance quality of life(SMD=0.50,95% CI:0.22 to 0.79,P<0.05,I^(2)=0%) in cancer patients after radiotherapy and chemotherapy,but it may not have a significant effect on *** risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2,and no studies were considered to be of high grade according to the GRADE ***:Aromatherapy is an efficacious,safe a

关键词： aromatherapy cancer chemoradiotherapy physical psychological

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Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

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Current medical Science 2024年第3期44卷 503-511页

作者： Jian-gang BI Qi LI Yu-sheng GUO Li-ping LIU Shi-yun BAO Ping XU Department of Hepatobiliary and Pancreatic Surgery Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Endocrinology Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China

Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC *** interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down *** RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western *** cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion *** HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal *** PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC ***,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each ***,PCED1B-AS1 increased the expression level of CD44,which was targeted by *** cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite ***,PCED1B-AS1 suppressed the role of ***,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in *** PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

关键词： long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1) hepatocellular carcinoma microRNA-34a(miR-34a) CD44 proliferation invasion

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