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Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro

World Journal of Stem Cells 2024年第2期16卷 163-175页

作者： Yan Ren Yan-Ni Cui Hong-Wei Wang The second Clinical medical College Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of Hematology The Second Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of Hematology Key Laboratory of Molecular Diagnosis and Treatment of Blood Diseases in Shanxi ProvinceTaiyuan 030001Shanxi ProvinceChina

BACKGROUND In vitro expansion to increase numbers of hematopoietic stem cells(HSCs)in cord blood could improve clinical efficacy of this vital ***(NAM)can promote HSC expansion ex vivo,but its effect on hematopoietic stem and progenitor cells(HSPCs,CD34^(+)CD38)and functional subtypes of HSCs-shortterm repopulating HSCs(ST-HSCs,CD34^(+)CD38CD45RACD49f^(+))and long-term repopulating HSCs(LT-HSCs,CD34^(+)CD38CD45RACD49f^(+)CD90^(+))is not yet *** a sirtuin 1(SIRT1)inhibitor,NAM participates in regulating cell adhesion,polarity,migration,proliferation,and ***,SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or *** propose that the concentration of NAM may influence proliferation,differentiation,and SIRT1 signaling of *** To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and *** CD34^(+)cells were purified from umbilical cord blood using MacsCD34 beads,and cultured for 10-12 d in a serum-free medium supplemented with cytokines,with different concentrations of NAM added according to experimental *** cytometry was used to detect phenotype,cell cycle distribution,and apoptosis of the cultured ***-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors,che mokines,components of hypoxia pathways,and antioxidant ***-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species(ROS).Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead *** Compared with the control group,the proportion and expansion folds of HSPCs(CD34^(+)CD38)incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased(all P<0.05).The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly

关键词： Hematopoietic stem cells Nicotinamide Concentration Proliferation Differentiation Sirtuin 1

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Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression

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Genes & Diseases 2024年第2期11卷 952-963页

作者： Zhenhao Zhang Doudou Jing Baijun Xuan Zhicai Zhang Wei Wu Zengwu Shao department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of Orthopedics The Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young ***,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than *** patients with osteosarcoma exhibit different characteristics compared to young patients,which usually results in a poor *** mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical *** cells can accelerate tumor progression by metabolic *** research has shown that methylmalonic acid(MMA)was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive *** found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma *** expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient ***,we first confirmed a novel molecular mechanism between cellular senescence and cancer,in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT ***,the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT *** conclusion,we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma,and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.

关键词： Cellular senescence Elderly patients MAFB-NOTCH3axis Methylmalonic acid Osteosarcoma PI3K-AKTpathway

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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit*

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Biomedical and Environmental Sciences 2024年第7期37卷 726-738页

作者： Xue F. Chen W. Lian X. He G. Tian J. Liu Y. Wang G. department of Neurology The Second Clinical School of Medicine Shanxi Medical University Shanxi Taiyuan 030002 China The second Clinical School of Medicine Shanxi Medical University Shanxi Taiyuan 030002 China department of Clinical lab The First People's Hospital of Zhaotong Yunnan Zhaotong 657000 China department of Neurology Sanya Central Hospital (Hainan Third People's Hospital) Hainan Medical University Hainan Sanya 57200 China

Objective: Intracranial hemorrhage (ICH), the second most common subtype of stroke, exacerbates the disruption of the blood-brain barrier (BBB), leading to vasogenic edema, plasma protein extravasation, and infiltration of neurotoxic substances. The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage. This study aimed to investigate the effect of circadian rhythms on BBB function, neuronal damage, and clearance capabilities. Methods: The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH. After intervention with different light groups, neuronal apoptosis was determined, glial phagocytosis was analyzed, the expression of endogenous clearing-related proteins aquaporin 4 (AQP4) and low-density lipoprotein receptor-related protein 1 (LRP1) was detected by western blotting and immunofluorescence dual standard method, and the expression of the tight junction protein occludin and melatonin receptor 1A (MTNR1A) was quantitatively analyzed. Results: Circadian rhythms play a key role in maintaining the integrity of the BBB, reducing oxidative stress-induced neuronal damage, and improving microglial phagocytosis. Meanwhile, the expression of occludin and MTNR1A in neurovascular unit (NVU) co-cultured with hemoglobin improved the expression of AQP4 and LRP1, the key proteins in the NVU's endogenous brain clearance system. Conclusion: Circadian rhythm (alternating black and white light) protects the NVU BBB function after ICH, promotes the expression of proteins related to the clearance of the hematoma, provides new evidence for the clinical treatment of patients recovering from ICH, and improves the circadian rhythm to promote brain metabolism and hematoma clearance. © 2024 The Editorial Board of Biomedical and Environmental Sciences

关键词： Aquaporin-4 Blood-brain barrier Circadian rhythm Melatonin receptor 1A Neurovascular unit

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New roles of tumor-derived exosomes in tumor microenvironment

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Chinese Journal of Cancer Research 2024年第2期36卷 151-166页

作者： Shiqian Chen Jinzhe Sun Huan Zhou Hongbin Lei Dan Zang Jun Chen department of Oncology the Second Hospital of Dalian Medical UniversityDalian 116023China department of Radiotherapy the Second Hospital of Dalian Medical UniversityDalian 116023China

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

关键词： Tumor-derived exosomes tumorigenesis tumor microenvironment diagnosis treatment

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Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of *** To explore the role of MTDH on stemness and immune infiltration in *** MTDH expression in HCC tissues was detected using TCGA and GEO *** was used to analyze the tissue *** was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell *** invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing ***,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free *** expression was determined by western blotting and quantitative reverse transcri-ption *** cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like *** effects of MTDH inhibition on tumor growth were evaluated in *** correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB *** HCC tissues expressed higher levels of MTDH than normal liver *** MTDH expression was associated with a poor *** cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these *** inhibition suppressed HCC progression and CD133 expression in *** was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T *** was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 a

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

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Carbon nanotubes-reinforced polylactic acid/hydroxyapatite porous scaffolds for bone tissue engineering

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Frontiers of Materials Science 2024年第1期18卷 59-69页

作者： Weiwei Lan Mingbo Wang Zhenjun Lv Jun Li Fuying Chen Ziwei Liang Di Huang Xiaochun Wei Weiyi Chen Research Center for Nano-Biomaterials&Regenerative Medicine Department of Biomedical EngineeringCollege of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan 030024China Guangdong Engineering Technology Research Center of Implantable medical Polymer Shenzhen Lando Biomaterials Co.Ltd.Shenzhen 518107China shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuan 030060China department of orthopaedics The Second Hospital of Shanxi Medical UniversityTaiyuan 030001China

In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite *** this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)*** results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through *** addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)***,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable ***,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.

关键词： CNTs/PLA/HA scaffold TIPS method mechanical property bone tissue engineering

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Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells

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Regenerative Biomaterials 2024年第2期3卷 76-87页

作者： Tao Lu Long Yang Zhuoyang Li Yin Liu Shun'en Xu Chuan Ye department of orthopaedics The Affliated Hospital of Guizhou Medical UniversityGuiyang 550004China department of orthopaedics The First People's Hospital of GuiyangGuiyang 550004China Center for Tissue Engineering and Stem Cell Research Guizhou Medical UniversityGuiyang 550004China department of Otolaryngology Head and Neck Surgery Xinqiao HospitalArmy Medical University(Third Military Medical University)Chongqing 400037China department of Dental implant Stomatological Hospital of GuiyangGuiyang 550000China

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(DEX)within the'fbers,ensuring sustained osteogenic *** scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were *** subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction *** fabricated P34HB ultrafine fiber slow-release *** ization *** distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active *** vitro tests showcased a prolonged release of DEX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular *** Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on ***,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 *** findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.

关键词： bone tissue engineering cell electrospinning in vivo induction immediate implantation biomaterials

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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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Bioinspired 4D Printing Shape-Memory Polyurethane Rhinoplasty Prosthesis for Dynamic Aesthetic Adjustment

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Journal of Bionic Engineering 2024年第3期21卷 1397-1411页

作者： Jiaqi Liu Guiwei Li He Liu Jincheng Wang Hui Wang Xue Gao Qingping Liu Chenyu Wang department of Plastic and Reconstructive Surgery The First Hospital of Jilin UniversityChangchun130021China department of orthopaedics The Second Hospital of Jilin UniversityChangchun130041China Key Laboratory of Bionic Engineering(Ministry of Education) Jilin UniversityChangchun130022China

The disparity between the postoperative outcomes of rhinoplasty and the expected results frequently necessitates secondary or multiple surgeries as a compensatory measure,greatly diminishing patient ***,there is renewed optimism for addressing these challenges through the innovative realm of Four-Dimensional(4D)*** groundbreaking technology enables three-dimensional objects with shape-memory properties to undergo predictable transformations under specific external ***,implants crafted using 4D printing offer significant potential for dynamic *** by worms in our research,we harnessed 4D printing to fabricate a Shape-Memory Polyurethane(SMPU)for use as a nasal augmentation *** choice of SMPU was guided by its Glass Transition Temperature(Tg),which falls within the acceptable temperature range for the human *** attribute allowed for temperature-responsive intraoperative self-deformation and postoperative *** chosen animal model for experimentation was *** into account the anatomical structure of the rabbit nose,we designed and produced nasal augmentation prostheses with superior *** prostheses were then surgically implanted in a minimally invasive manner into the rabbit ***,they exhibited successful temperature-controlled in-surgery self-deformation according to the predetermined shape and non-invasive remodeling within a mere 9 days *** histological evaluations confirmed the practical viability of these prostheses in a living *** research findings posit that worm-inspired 4D-printed SMPU nasal prostheses hold significant promise for achieving dynamic aesthetic adjustments.

关键词： 4D printing Shape memory polyurethane Rhinoplasty Self-deformation Dynamic aesthetic adjustment

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