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Extracellular vesicles derived from mesenchymal stem cells:the wine in Hebe's hands to treat skin aging

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Precision Clinical Medicine 2024年第2期7卷 170-189页

作者： Qixiang Gui Neng Ding Zuochao Yao Minjuan Wu Ruifeng Fu Yue Wang Yunpeng Zhao Lie Zhu Department of Plastic and Reconstructive Surgery Second Affliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)Shanghai 20o001China Department of Plastic and Reconstructive Surgery of Shanghai East Hospital School of MedicineTongji UniversityShanghai 200120China Department of Histology and Embryology Naval Medical UniversityShanghai 200433China Shanghai Key Laboratory of cell Engineering Translational Medical Research CenterNaval Medical UniversityShanghai 200433China hanghai Institute of stem cell research and Clinical Translation Shanghai 200092China

Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of *** and delaying skin aging has become one of the prominent research subjects in recent *** stem celis(MsCs)are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation ***-derived extracellular vesicles(MSC-EVs)are nanoscale biological vesicles that facilitate intercellular communication and regulate biological *** studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory,anti-oxidative stress,and wound healing promoting *** review presents the latest progress of MSC-EVs in delaying skin *** mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts,reducing the expression of matrix metalloproteinases,resisting oxidative stress,and regulating *** then briefly discuss the recently discovered treatment methods of MSc-EVs in the field of skin ***,the advantages and limitations of EV-based treatments are also presented.

关键词： mesenchymal stem cell extracellular vesicles exosomes skin aging anti-aging photoaging

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

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Oncology research 2024年第1期32卷 49-60页

作者： QIUQIANG CHEN XUEJUN GUO WENXUE MA Key Laboratory for Translational Medicine The First Affiliated HospitalHuzhou University School of MedicineHuzhou313000China Department of Hematology Puyang Youtian General HospitalPuyang457001China Department of Medicine Moores Cancer CenterSanford Stem Cell InstituteUniversity of California San DiegoLa JollaSan Diego92093USA

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune ***47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer ***,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely *** comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell ***,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic *** review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting *** the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if ***,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment ***,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

关键词： CD47 Cancer immunotherapy CD47-targeted therapies Tumor microenvironment Macrophage Cancer cell Immune evasion Checkpoint inhibitors CAR T-cell therapy Cancer treatment outcomes

Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and stem cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering research center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of stem cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (PTEN) in sensitivity of acute myeloid leukemia to chemotherapy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 700-710页

作者： Liming LIN Jingjing TAO Ying MENG Yichao GAN Xin HE Shu LI Jiawei ZHANG Feiqiong GAO Dijia XIN Luyao WANG Yili FAN Boxiao CHEN Zhimin LU Yang XU Department of Hematology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated Hospital and Institute of Translational MedicineCancer CenterZhejiang University School of MedicineHangzhou 310029China Institute of Genetics Zhejiang UniversityHangzhou 310058China Division of Hematopoietic stem cell&Leukemia research Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Hematology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most ***,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)***101 suppresses the proliferation of myeloid malignancy cells and primary AML *** induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 *** knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling *** inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell *** findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

关键词： Genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library Phosphatase and tensin homologous(PTEN) Rapamycin Acute myeloid leukemia(AML) Chemotherapy

The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

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Journal of Bionic Engineering 2024年第2期21卷 924-937页

作者： Sharareh Ghaziof Shahrokh Shojaei Mehdi Mehdikhani Mohammad Khodaei Milad Jafari Nodoushan Department of Biomedical Engineering Central Tehran BranchIslamic Azad UniversityTehran***Iran stem cells research center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran Department of Biomedical Engineering Faculty of EngineeringUniversity of IsfahanIsfahan***Iran Materials Engineering Group Golpayegan College of EngineeringIsfahan University of TechnologyGolpayegan87717-67498Iran Hard Tissue Engineering research center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of *** this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the ***,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were *** microstructural observation of the scaffolds reported interconnected pores with 150–300µm in *** 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D *** release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th *** addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved *** findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

关键词： Polycaprolactone Gold nanoparticles Drug delivery systems Spironolactone cell behavior Myoblasts

Enhanced angiogenesis in porous poly(ε-caprolactone) scaffolds fortified with methacrylated hyaluronic acid hydrogel after subcutaneous transplantation

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Biomaterials Translational 2024年第1期5卷 59-68页

作者： Yang H. Zheng M. Zhang Y. Li C. Lai J.H.C. Zhang Q. Chan K.W.Y. Wang H. Zhao X. Yang Z. Xu C. Department of Biomedical Engineering City University of Hong Kong Hong Kong center for Pluripotent stem cell research and Engineering Research Institute of Tsinghua Guangdong Province Guangzhou China Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Hong Kong

A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment, survival, and retention in cell transplantation processes. This study presents a composite scaffold made of poly(ε-caprolactone) (PCL) and methacrylated hyaluronic acid (MeHA) hydrogel and describes the corresponding physical properties (surface area, porosity, and mechanical strength) and host response (angiogenesis and fibrosis) after subcutaneous transplantation. Specifically, we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities. Subsequently, we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds. In experiments with mice, the scaffold composed of 3% PCL and 10–100 kDa, degree of substitution 70% MeHA results in the least fibrosis and a higher degree of angiogenesis. This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation, given their desirable physical properties and host response. © 2024, Chinese Medical Multimedia Press Co Ltd. All rights reserved.

关键词： angiogenesis cell transplantation hyaluronic acid poly(ε-caprolactone) scaffold

Impact of umbelliprenin-containing niosome nanoparticles on VEGF-A and CTGF genes expression in retinal pigment epithelium cells

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 7-15页

作者： Farzad Dastaviz Akram Vahidi Teymoor Khosravi Ayyoob Khosravi Mehdi Sheikh Arabi Abouzar Bagheri Mohsen Rashidi Morteza Oladnabi stem cell research center Golestan University of Medical SciencesGorgan ***Iran Department of Medical Genetics School of Advanced Technologies in MedicineGolestan University of Medical SciencesGorgan ***Iran Student research Committee Golestan University of Medical SciencesGorgan ***Iran Department of Molecular Medicine Faculty of Advanced Medical TechnologiesGolestan University of Medical SciencesGorgan ***Iran Department of Medical Nanotechnology Faculty of Advanced Medical TechnologiesGolestan University of Medical SciencesGorgan ***Iran Department of Clinical Biochemistry and Genetics Faculty of MedicineMazandaran University of Medical SciencesSari ***Iran Department Pharmacology Faculty of MedicineMazandaran University of Medical SciencesSari ***Iran Gorgan Congenital Malformations research center Golestan University of Medical SciencesGorgan ***Iran

AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective tissue growth factor(CTGF)genes in a human retinal pigment epithelium(RPE)-like retina-derived cell ***:UMB-containing niosomes were created,optimized,and ***-like cells were treated with free UMB and UMB-containing *** IC_(50)values of the treatments were determined using an MTT *** expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA ***’characteristics,including drug entrapment efficiency,size,dispersion index,and zeta potential were *** UMB had an IC_(50)of 96.2μg/mL,while UMB-containing niosomes had an IC_(50)of 25μg/***:Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells(P=0.001).Additionally,UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells(P=0.05).However,there was no significant reduction in the expression of both genes in cells treated with free ***:Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes ***,the latter demonstrates significantly greater efficacy,potentially due to the lower UMB dosage and gradual *** findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

关键词： umbelliprenin niosome age-related macular degeneration vascular endothelial growth factor-A connective tissue growth factor

RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

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Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family center for Leukemia research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2