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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-Jin Ai Ling-Juan Chen Li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao department of Laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese medicine Regulating metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional *** acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting *** To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact *** In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was *** expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading *** induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and *** was also found to downregulate FOXM1 indirectly by regulating ***,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial *** inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of ***,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial *** Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2581-2597页

作者： Hongliang Qiu Sihui Huang Yuting Liu Libo Liu Fengming Guo Yingying Guo Dan Li Xianfeng Cen Yajie Chen Meng Zhang Yan Che Man Xu Qizhu Tang department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China Hubei Key Laboratory of metabolic and Chronic Diseases Wuhan 430060China

Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively *** was recently identified as a major mechanism of DOX-induced ***,a novel ferroptosis inhibitor,is a well-described clinical drug widely ***,its role and pathological mechanism in DOX-induced cardiotoxicity are still *** this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced *** results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in *** and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by ***,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of *** could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with *** results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination *** conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.

关键词： Idebenone DOX-induced cardiotoxicity Ferroptosis FSP1 Ubiquitination Lipid peroxidation Iron overload Clinical translation

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Cuproptosis mediates copper-induced testicular spermatogenic cell death

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Asian Journal of Andrology 2024年第3期26卷 295-301页

作者： Jing-Yi Zhang Xu-Jun Yu Jun-Jun Li Yao Xiao Guang-Sen Li Fang Yang Liang Dong Chengdu university of Traditional Chinese medicine Chengdu 611137China Chengdu Fifth People’s Hospital The Fifth People’s Hospital of Chengdu University of Traditional Chinese MedicineChengdu 611130China TCM Regulating metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China department of Surgery The Reproductive and Women-Children HospitalChengdu University of Traditional Chinese MedicineChengdu 610041China

Cuproptosis,a novel mechanism of programmed cell death,has not been fully explored in the context of spermatogenic *** investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper *** male Institute of Cancer Research(ICR)mice were randomly divided into four groups that received daily oral gavage withsodium chloride(control)or copper sulfate(CuSO_(4))at 50 mg kg^(−1),100 mg kg^(−1),or 200 mg kg^(−1),for 42 consecutive *** to copper overload exhibited a disruption in copper ***,significant upregulated expression of keycuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell *** revealed the presence of ferredoxin 1(Fdx1)in Sertoli cells,Leydig cells,and spermatogenic cells at various stages oftesticular development,and the Fdx1-positive staining area was significantly increased in copper-overloaded *** and decreased adenosine triphosphate levels were also observed,further implicating mitochondrial damage *** analyses revealed pathological lesions and blood−testis barrier destruction in the testicular tissue,accompaniedby decreased sperm concentration and motility,in copper-overloaded *** summary,our results indicate that copper-overloadedmice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell *** findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initialexperimental evidence for the occurrence of cuproptosis in the testis.

关键词： blood−testis barrier cuproptosis ferredoxin 1 spermatogenic cell death

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Molecular biomarkers for vascular cognitive impairment and dementia:the current status and directions for the future

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Neural Regeneration Research 2024年第12期19卷 2579-2580页

作者： Satoshi Hosoki Perminder SSachdev Centre for Healthy Brain Ageing Discipline of Psychiatry and Mental HealthSchool of Clinical MedicineFaculty of Medicine and HealthUniversity of New South WalesSydneyAustralia department of Neurology National Cerebral and Cardiovascular CenterOsakaJapan

Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive *** development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological ***,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.

关键词： prevention diagnosis impairment

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin Feng Weining Hu Mengyao Dai Xiaohui Sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan Cao department of Endocrine and metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research Center for Translational medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research Center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Large-scale manufacturing of functional single-atom ink for convenient glucose sensing

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Nano Research 2024年第8期17卷 7256-7263页

作者： Muyu Yan Xiaofei Zhu Can Xiong Xiao Han Zhenggang Xue Yuen Wu department of Endocrinology Institute of Endocrine and Metabolic DiseasesThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Deep Space Exploration Laboratory University of Science and Technology of ChinaHefei 230026China NEST Laboratory Department of PhysicsDepartment of ChemistryCollege of ScienceShanghai UniversityShanghai 200444China Center of Advanced Nanocatalysis(CAN) Department of Applied ChemistryUniversity of Science and Technology of ChinaHefei 230026China

Printing techniques hold great potential in the manufacture of electronics such as sensors,micro-supercapacitors,and flexible ***,developing large-scale functional conductive inks with appropriate rheological properties and active components still remains a ***,through optimizing the formulations of ink,iron single sites supported N-doped carbon black(Fe_(1)-NC)inks can serve as both conductive electrodes and high-reactive catalysts to realize convenient glucose detection,which pronouncedly reduces the dosage of enzyme and simplifies the sensors *** detail,utilizing in-situ pyrolysis method,Fe_(1)-NC single-atom catalysts(SACs)are prepared in bulk(dekagram-level).The batched Fe_(1)-NC SACs materials can be uniformly mixed with modulated ink to realize the screen printing with high resolution and ***,the whole scalable preparation and ink-functional process can be extended to various metals(including Co,Ni,Cu,and Mn).The introduction of highly active Fe_(1)-NC sites reduces the amount of enzyme used in glucose detection by at least 50%,contributing to the cost reduction of *** strategy in harnessing the SACs onto the carbon inks thus provides a broad prospect for the low-cost and large-scale printing of sensitive sensing devices.

关键词： large-scale manufacturing single-atom inks screen printing glucose sensing low enzyme dosage

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Exercise-induced microbial changes in preventing type 2 diabetes

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Science China(Life Sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui Wang Kaiqing Lin Ruwen Wang Shanshan Guo Peijie Chen Hao Wu Tiemin Liu Ru Wang School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai Key Laboratory of metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China State Key Laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China State Key Laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut *** we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and *** found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students *** additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance ***,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation *** propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

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VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

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World Journal of Stem Cells 2024年第2期16卷 207-227页

作者： Yun Yuan Xu-Fan Zhang Yu-Chen Li Hong-Qing Chen Tian Wen Jia-Lian Zheng Zi-Yi Zhao Qiong-Ying Hu department of Laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina department of Nuclear medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina department of Hepatology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110032Liaoning ProvinceChina Hospital of Chengdu university of Traditional Chinese medicine Chengdu 610072Sichuan ProvinceChina Traditional Chinese medicine Regulating metabolic Diseases Key Laboratory of Sichuan Province Chengdu 610072Sichuan ProvinceChina

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)*** are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of ***,targeting this specific subpopulation has been recognized as a promising strategy for overcoming *** To investigate the effect of VX-509 on CCSCs and elucidate the underlying *** CCSCs were enriched from CRC cell lines by in conditioned serum-free *** blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the *** anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in *** Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC ***-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in ***,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in *** was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database ***-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT ***,VX-509 rev

关键词： Colorectal cancer stem cells Stemness VX-509 Epithelial-mesenchymal transition Nodal

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Fluorescence‑Based Calibration Model for In‑Situ Measurement of Micro‑scaled Lubricant Thickness Distribution at Indentation Interface

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Nanomanufacturing and Metrology 2024年第2期7卷 76-88页

作者： Motoya Yoshikawa Saeko Fujii Shotaro Kadoya Tatsuya Sugihara Masaki Michihata Satoru Takahashi department of Precision Engineering The University of TokyoHongo 7‑3‑1BunkyoTokyo 113‑8656Japan department of Mechanical Engineering Osaka UniversityYamadaoka 2‑1SuitaOsaka 565‑0871Japan

This study proposes a model for the measurement of microscale liquid film thickness distribution using fluorescence *** interfacial conditions between the tool and the workpiece in mechanical machining are important for understanding these phenomena and *** this study,indentation tests with transparent tools were used to observe interfaces;however,it was challenging to obtain the signal from a thin fluorescent liquid film on smooth and steeply inclined ***,fluorescence-based measurement,such as laser-induced fluorescence,was *** measure the absolute thickness of the thin fluorescent film,calibration of the measurement system is ***,a theoretical model was proposed considering the multiple reflections of excitation light and fluorescence at the inclined surface between the indenter and *** measuring the profile of the surface topography of the indented workpiece and comparing the results with those measured by a surface profiler,the validity of the proposed calibration method and the performance of this measurement system were *** measured surface profiles,including scratches of 2–4μm,were in good agreement,demonstrating the validity of the proposed method.

关键词： Laser-induced fluorescence(LIF) Thickness distribution In-situ measurement Lubricant Mechanical machining

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Drawing lines in the sand: The growing threat of obesity in type 1 diabetes

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World Journal of Diabetes 2024年第5期15卷 823-827页

作者： Theocharis Koufakis Dimitrios Patoulias Ioanna Zografou Nikolaos Papanas Djordje S Popovic Second Propedeutic department of Internal medicine Aristotle University of ThessalonikiThessaloniki 54642Greece Diabetes Centre Second Department of Internal MedicineDemocritus University of ThraceAlexandroupolis 68100Greece Clinic for Endocrinology Diabetes and Metabolic DisordersClinical Center of VojvodinaMedical FacultyUniversity of Novi SadNovi Sad 21000Serbia

In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in *** focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this *** exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in *** our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of *** regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes *** this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

关键词： Obesity Overweight Type 1 diabetes metabolic syndrome

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