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High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1βproduction in monocytes:the modulatory effects of EGCG

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Food Science and Human Wellness 2024年第3期13卷 1531-1542页

作者： Chi-Hao Wu Yin-Hsuan Chang Chin-Lin Hsu Sheng-Yi Chen Gow-Chin Yen Graduate Programs of Nutrition Science School of Life ScienceTaiwan Normal UniversityTaipei 106209TaiwanChina Department of Food Science and Biotechnology Chung Hsing UniversityTaichung 40227TaiwanChina School of Nutrition Chung Shan Medical UniversityTaichung 40201TaiwanChina

Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human ***,the molecular mechanisms underlying sRAGE remain *** this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)*** modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also *** enhanced intracellular reactive oxygen species(ROS)generation and RAGE *** secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear ***,the HG effects were counteracted by siRAGE and exacerbated by *** immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this *** data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating *** HG conditions,the treatment of EGCG reduced ROS generation and RAGE ***-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 *** inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.

关键词： Epigallocatechin gallate(EGCG) Inflammasome Nuclear factor erythroid 2-related factor 2(Nrf2) Receptor for advanced glycation end products(RAGE) Soluble RAGE(sRAGE)

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Ten- year follow- up investigation of stroke risk in systemic lupus erythematosus

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Stroke & Vascular Neurology 2024年第1期9卷 1-7页

作者： Jin-An Huang Ching-Heng Lin Ming-Ju Wu Yi-Hsing Chen Kuo-Cheng Chang chung-Wei Hou Division of Neurology Neurological InstituteTaichung Veterans General HospitalTaichungTaiwan Department of Health Business Administration Hungkuang UniversityTaichungTaiwan Department of medical Research Taichung Veterans General HospitalTaichungTaiwan Division of Nephrology Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine Chung Shan Medical UniversityTaichungTaiwan College of Medicine National Chung Hsing UniversityTaichungTaiwan Division of Allergy Immunology and RheumatologyDepartment of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine National Yang-Ming Chiao Tung UniversityTaichungTaiwan

Background and purpose To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus(SLE).Methods A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research *** with SLE between 2000 and 2008 were registered and matched with two controls by the index date,age,gender and Charlson Comorbidity Index(CCI).These subjects were followed until either stroke event or 31 December *** HRs(aHRs)for strokes were estimated with Cox regression models,and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival *** In total,8310 patients with SLE and 16620 patients without SLE were *** general,patients with SLE had higher rates of ischaemic stroke(5.4%vs 3.3%)and haemorrhagic stroke(1.5%vs 0.6%)than in *** multivariate analysis adjusted to age,gender,CCI,urbanisation level and antithrombotics uses,aHRs of all strokes,ischaemic stroke and haemorrhagic stroke were 1.73(95%CI:1.54 to 1.94),1.65(95%CI:1.45 to 1.87)and 2.24(95%CI:1.71 to 2.95),respectively,in patients with *** with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE,even 10 years after SLE diagnosis(6.12%vs 3.50%,p<0.001).Antiplatelet use increased the risk of haemorrhagic stroke in SLE group(aHR=1.74,95%CI:1.18 to 2.57).Conclusions Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 *** should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

关键词： erythematosus diagnosis likely

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Coupling Analysis of Multiple Machine Learning Models for Human Activity Recognition

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Computers, Materials & Continua 2024年第6期79卷 3783-3803页

作者： Yi-Chun Lai Shu-Yin Chiang Yao-Chiang Kan Hsueh-Chun Lin Department of Public Health China Medical UniversityTaichung406040Taiwan Department of Information and Telecommunications Engineering Ming Chuan UniversityGui-ShanTaoyuan333Taiwan Department of Electrical Engineering Yuan Ze UniversityChung-Li32003Taiwan Department and Institute of Health Service Administrations China Medical UniversityTaichung406040Taiwan

Artificial intelligence(AI)technology has become integral in the realm of medicine and healthcare,particularly in human activity recognition(HAR)applications such as fitness and rehabilitation *** study introduces a robust coupling analysis framework that integrates four AI-enabled models,combining both machine learning(ML)and deep learning(DL)approaches to evaluate their effectiveness in *** analytical dataset comprises 561 features sourced from the UCI-HAR database,forming the foundation for training the ***,the MHEALTH database is employed to replicate the modeling process for comparative purposes,while inclusion of the WISDM database,renowned for its challenging features,supports the framework’s resilience and *** ML-based models employ the methodologies including adaptive neuro-fuzzy inference system(ANFIS),support vector machine(SVM),and random forest(RF),for data *** contrast,a DL-based model utilizes one-dimensional convolution neural network(1dCNN)to automate feature ***,the recursive feature elimination(RFE)algorithm,which drives an ML-based estimator to eliminate low-participation features,helps identify the optimal features for enhancing model *** best accuracies of the ANFIS,SVM,RF,and 1dCNN models with meticulous featuring process achieve around 90%,96%,91%,and 93%,*** analysis using the MHEALTH dataset showcases the 1dCNN model’s remarkable perfect accuracy(100%),while the RF,SVM,and ANFIS models equipped with selected features achieve accuracies of 99.8%,99.7%,and 96.5%,***,when applied to the WISDM dataset,the DL-based and ML-based models attain accuracies of 91.4%and 87.3%,respectively,aligning with prior research *** conclusion,the proposed framework yields HAR models with commendable performance metrics,exhibiting its suitability for integration into the healthcare services system through AI-driven applications.

关键词： Human activity recognition artificial intelligence support vector machine random forest adaptive neuro-fuzzy inference system convolution neural network recursive feature elimination

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An artificial intelligence diabetes management architecture based on 5G

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Digital Communications and Networks 2024年第1期10卷 75-82页

作者： Ruochen Huang Wei Feng shan Lu Tao shan Changwei Zhang Yun Liu Department of Geriatrics The First Affiliated Hospital of Nanjing Medical UniversityNanjing210096China Department of Information The First Afliated Hospital of Nanjing Medical UniversityNanjing210096China Department of medical Informatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing211166China Department of Outpatient The First Affiliated Hospital of Nanjing Medical UniversityNanjing210096China Jiangsu Key Laboratory of Wireless Communications Nanjing University of Posts and TelecommunicationsNanjing210003China

Along with the development of 5G network and Internet of Things technologies,there has been an explosion in personalized healthcare *** the 5G and Artificial Intelligence(Al)is introduced into diabetes management architecture,it can increase the efficiency of existing systems and complications of diabetes can be handled more effectively by taking advantage of *** this article,we propose a 5G-based Artificial Intelligence Diabetes Management architecture(AIDM),which can help physicians and patients to manage both acute complications and chronic *** AIDM contains five layers:the sensing layer,the transmission layer,the storage layer,the computing layer,and the application *** build a test bed for the transmission and application ***,we apply a delay-aware RA optimization based on a double-queue model to improve access efficiency in smart hospital wards in the transmission *** application layer,we build a prediction model using a deep forest *** on real-world data show that our AIDM can enhance the efficiency of diabetes management and improve the screening rate of diabetes as well.

关键词： Diabetes 5G Artificial intelligence Deep forest Smart hospital ward

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Outcomes of combined mitochondria and mesenchymal stem cellsderived exosome therapy in rat acute respiratory distress syndrome and sepsis

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World Journal of Stem Cells 2024年第6期16卷 690-707页

作者： Kun-Chen Lin Wen-Feng Fang Jui-Ning Yeh John Y Chiang Hsin-Ju Chiang Pei-Lin Shao Pei-Hsun Sung Hon-Kan Yip Department of Anesthesiology Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina Division of Pulmonary and Critical Care Medicine Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiung 83301TaiwanChina Department of Cardiology The First Affiliated Hospital of Jinan UniversityGuangzhou 510630Guangdong ProvinceChina Department of Computer Science and Engineering National Sun Yat-sen UniversityKaohsiung 804201TaiwanChina Department of Healthcare Administration and medical Informatics Kaohsiung Medical UniversityKaohsiung 80708TaiwanChina School of Medicine Chung Shan Medical UniversityTaichung 40201TaiwanChina Department of Nursing Asia UniversityTaichung 41354TaiwanChina Division of Cardiology Department of Internal MedicineKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung 83301TaiwanChina Institute for Translational Research in Biomedicine Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina Center for Shockwave Medicine and Tissue Engineering Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina Department of medical Research China Medical University HospitalChina Medical UniversityTaichung 40402TaiwanChina School of Medicine College of MedicineChang Gung UniversityTaoyuan 33302TaiwanChina

BACKGROUND The treatment of acute respiratory distress syndrome(ARDS)complicated by sepsis syndrome(SS)remains *** To investigate whether combined adipose-derived mesenchymal-stem-cells(ADMSCs)-derived exosome(EXAD)and exogenous mitochondria(mitoEx)protect the lung from ARDS complicated by *** In vitro study,including L2 cells treated with lipopolysaccharide(LPS)and in vivo study including male-adult-SD rats categorized into groups 1(sham-operated-control),2(ARDS-SS),3(ARDS-SS+EXAD),4(ARDS-SS+mitoEx),and 5(ARDS-SS+EXAD+mitoEx),were included in the present *** In vitro study showed an abundance of mitoEx found in recipient-L2 cells,resulting in significantly higher mitochondrial-cytochrome-C,adenosine triphosphate and relative mitochondrial DNA levels(P<0.001).The protein levels of inflammation[interleukin(IL)-1β/tumor necrosis factor(TNF)-α/nuclear factor-κB/toll-like receptor(TLR)-4/matrix-metalloproteinase(MMP)-9/oxidative-stress(NOX-1/NOX-2)/apoptosis(cleaved-caspase3/cleaved-poly(ADP-ribose)polymerase)]were significantly attenuated in lipopolysaccharide(LPS)-treated L2 cells with EXAD treatment than without EXAD treatment,whereas the protein expressions of cellular junctions[occluding/β-catenin/zonula occludens(ZO)-1/E-cadherin]exhibited an opposite pattern of inflam-mation(all P<0.001).Animals were euthanized by 72 h post-48 h-ARDS induction,and lung tissues were *** 72 h,flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflam-matory cells(Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+)and albumin were lowest in group 1,highest in group 2,and significantly higher in groups 3 and 4 than in group 5(all P<0.0001),whereas arterial oxygen-saturation(SaO2%)displayed an opposite pattern of albumin among the *** findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers(CD68+/γ-H2AX)displayed an identical pattern of SaO2%among the groups(all P<0.0001).The pro

关键词： Acute respiratory distress syndrome Sepsis syndrome Exosomes Mitochondria Adipose tissue-derived mesenchymal stem cells Inflammation

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IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of shandong university of Traditional Chinese Medicine JinanShandong 250355China Department of Reproductive Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease *** these rare cancer cells,however,remains challenging with respect to therapeutic ***,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid *** expression of IL-13RA2 was positively correlated with canonical stemness markers in *** further demonstrated that the level of IL-13 was up-regulated in the serum of CRC ***,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in *** phenotype could be reversed by knocking down ***,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of *** further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of *** conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

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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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Design,synthesis,and biological evaluation of novel chrysin derivatives as poly(ADP-ribose)polymerase 1(PARP1)inhibitors for the treatment of breast cancer

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Chinese Journal of Natural Medicines 2024年第5期22卷 455-465页

作者： YANG Yao TONG Jing XIE Xianshun CAO Hong FU Yong LUO Yong LIU shan CHEN Wen YANG Ning Hengyang medical School University of South ChinaHengyang 421200China Emergency Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hengyang medical School The Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hemato-oncology Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Department of Breast and Thyroid Surgery Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China

In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA ***,5d induced apoptosis and caused an extended G1/S-phase in these cell *** docking studies revealed that 5d possesses a strong binding affinity toward *** vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 ***,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

关键词： Chrysin derivatives PARP1 Antitumor DNA damage Small molecules

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Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

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BIOCELL 2024年第8期48卷 1265-1273页

作者： shan JIANG XIUFENG LIN YANFEI CHEN XINNING LI JIALI KANG Department of Gynecology and Obstetrics The First Affiliated Hospital of Jinan UniversityGuangzhou510180China Reproductive medical Center Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhou510180China

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor *** has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and ***,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still ***:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian *** assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer *** pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer ***:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian *** experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this ***,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

关键词： Ultra-conserved non-coding RNA uc.243 Drug efflux Drug transporters Chemoresistance Ovarian cancer

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Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1564-1577页

作者： Sai-Nan Li shan Yang Hao-Qi Wang Tian-Li Hui Meng Cheng Xi Zhang Bao-Kun Li Gui-Ying Wang The First Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina The Second Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina Department of General Surgery The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality *** to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient *** noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain *** To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this *** Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin *** bioinformatics tools were employed to elucidate molecular *** expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain *** assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA *** between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream ***,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy *** LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)*** was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 *** expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing *** RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of *** PRNT/ZNF184

关键词： Colorectal cancer Oxaliplatin resistance Prion protein testis specific Zinc finger protein 184 Homeodomain interacting protein kinase 2

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