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Adipose-derived mesenchymal stem cells(MSCs)are a superior cell source for bone tissue engineering 被引量:4
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作者 Yannian Gou Yanran Huang +18 位作者 Wenping Luo Yanan Li Piao Zhao Jiamin Zhong Xiangyu Dong Meichun Guo Aohua Li Ailing Hao Guozhi Zhao Yonghui Wang Yi Zhu Hui Zhang Yunhan Shi William Wagstaff Hue H.Luu Lewis L.Shi Russell R.Reid Tong-Chuan He jiaming fan 《Bioactive Materials》 SCIE CSCD 2024年第4期51-63,共13页
Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most pro... Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most promising seed cells for bone tissue engineering.As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat,MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.To identify an optimal progenitor cell source for bone tissue engineering,we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources,including immortalized mouse embryonic fibroblasts(iMEF),immortalized mouse bone marrow stromal stem cells(imBMSC),immortalized mouse calvarial mesenchymal progenitors(iCAL),and immortalized mouse adipose-derived mesenchymal stem cells(iMAD).We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro,whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair.Transcriptomic analysis revealed that,while each MSC line regulated a distinct set of target genes upon BMP9 stimulation,all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt,TGF-β,PI3K/AKT,MAPK,Hippo and JAK-STAT pathways.Collectively,our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering. 展开更多
关键词 Mesenchymal stem cell(MSC) Bone tissue engineering Multipotent progenitor cells Adipose-derived mesenchymal stem cells Osteogenic differentiation ADIPOGENESIS
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Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model 被引量:1
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作者 Meichun Guo Yannian Gou +5 位作者 Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He jiaming fan 《Genes & Diseases》 SCIE CSCD 2024年第4期28-30,共3页
Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and MCT4.Previous studies have... Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and MCT4.Previous studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate. 展开更多
关键词 HYPERTENSIVE MCT1 DRUG
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A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine 被引量:1
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作者 Xiangyu Dong Yannian Gou +10 位作者 Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng Rex C.Haydon Hue H.Luu Russell R.Reid Tongchuan He Yan Xu jiaming fan 《Genes & Diseases》 SCIE CSCD 2024年第3期26-29,共4页
With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogene... With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods. 展开更多
关键词 TRANSPORT METHODS simplified
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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities
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作者 Michael Yu Kevin Qin +16 位作者 jiaming fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He 《Genes & Diseases》 SCIE CSCD 2024年第3期155-187,共33页
The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.Wnt proteins are secreted,lipid-modified signaling molecules that activate the canoni... The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.Wnt proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling pathways.Cellular behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling paths.Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues.This includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem cells.Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties.Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders.Not surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including cancer.Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and metastasis.Altogether,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway.Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies. 展开更多
关键词 β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling
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GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus
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作者 Guozhi Zhao Piao Zhao +21 位作者 Yonghui Wang Hui Zhang Yi Zhu Jiamin Zhong Wulin You Guowei Shen Changi Luo Ou Mei Xingye Wu Jingjing Li Yi Shu Hongwei Wang Wiliam Wagstaff Hue HLuu Yang Bi Lewis LShi Russell RReid Tong-Chuan He Li Jiang Wei Tang jiaming fan Ziwei Tang 《Genes & Diseases》 SCIE CSCD 2024年第6期367-380,共14页
Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv inf... Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv infection-associated oxidative stress and reactive oxygen species(ROS)production.Here,we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells,and expedites adenovirus production.By stably overexpressing GAPDH in HEK293(293G)and 293pTP(293GP)cells,respectively,we demonstrated that rAdV-induced RoS production and cell apoptosis were significantly suppressed in 293G and 293GP cells.Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells.Similarly,Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells.We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells.293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells,indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production.These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production.Therefore,the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy. 展开更多
关键词 GAPDH GENETHERAPY Oxidative stress Packaging cell line Reactive oxygen species Recombinant adenovirus
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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk
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作者 Kevin Qin Michael Yu +18 位作者 jiaming fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi 《Genes & Diseases》 SCIE CSCD 2024年第1期103-134,共32页
Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors an... Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling. 展开更多
关键词 β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk
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Association of creatine kinase with Alzheimer’s disease pathology:A cross-sectional study
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作者 Yutong Wang Peiyang Gao +4 位作者 Hongman Liu Tingyu Wang jiaming fan Tingbo Jiang Alzheimer’s Disease Neuroimaging Initiative(ADNI) 《Chinese Medical Journal》 SCIE CAS CSCD 2024年第1期117-119,共3页
To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and mitochondria.It can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,a... To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and mitochondria.It can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,and pericarditis because it is a vital kinase directly related to intracellular energy operation,muscle contraction,and adenosine triphosphate(ATP)regeneration.Several studies have confirmed in recent years that serum biomarkers such as elevated CK are associated with Alzheimer’s disease(AD)and its related pathological protein.[1]Previous research indicated that systemic conditions,particularly cardiovascular and cerebrovascular diseases,are significant risk factors for cognitive impairment,and dysfunction of peripheral organs may also contribute to cognitive decline and AD.[2]However,the connection between CK and AD remains unknown.Therefore,to investigate the association between CK and cerebrospinal fluid(CSF)AD pathology biomarkers,we analyzed data from the Alzheimer’s Disease Neuroimaging Initiative(ADNI),a global multi-centered database. 展开更多
关键词 ALZHEIMER PATHOLOGY ORGANS
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Long noncoding RNA(lncRNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases 被引量:2
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作者 Junyi Liao Bowen Chen +18 位作者 Zhenglin Zhu Chengcheng Du Shengqiang Gao Guozhi Zhao Piao Zhao Yonghui Wang Annie Wang Zander Schwartz Lily Song Jeffrey Hong William Wagstaff Rex CHaydon Hue HLuu jiaming fan Russell RReid Tong-Chuan He Lewis Shi Ning Hu Wei Huang 《Genes & Diseases》 SCIE CSCD 2023年第4期1351-1366,共16页
Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of... Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions. 展开更多
关键词 CANCER Epigenetic regulation H19 LncRNA Long-noncoding RNA Metabolic diseases Stem cell differentiation
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SV40 large T antigen-induced immortalization reprograms mouse cardiomyocyte progenitors with mesenchymal stem cell characteristics and osteogenic potential 被引量:1
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作者 Yichun Yu Jiamin Zhong +13 位作者 Connie Chen Yannian Gou Guozhi Zhao Piao Zhao Yonghui Wang Wei Zeng Annie Wang William D.Wagstaff Jr Rex C.Haydon Tong-Chuan He Russell R.Reid Michael J.Lee Hue H.Luu jiaming fan 《Genes & Diseases》 SCIE CSCD 2023年第4期1161-1164,共4页
While progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart,primary cardiomyogenic progenitors(CPs)have a limited life span in culture,hampering the use of CPs for in vitro... While progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart,primary cardiomyogenic progenitors(CPs)have a limited life span in culture,hampering the use of CPs for in vitro and in vivo studies.We previously isolated primary CPs from mouse E15.5 fetal heart,and reversibly immortalized them with SV40 large T antigen(SV40 LTA),resulting in immortalized CPs(iCPs),which maintain long-term proliferation and ex-press cardiomyogenic markers and retain differentiation potential under appropriate differentiation conditions. 展开更多
关键词 PROGENITOR cardio potential
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The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine 被引量:19
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作者 Sami Mostafa Mikhail Pakvasa +26 位作者 Elam Coalson Allen Zhu Alex Alverdy Hector Castillo jiaming fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid 《Genes & Diseases》 SCIE 2019年第3期201-223,共23页
Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and c... Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. 展开更多
关键词 ADIPOGENESIS Bone morphogenetic proteins(BMPs) BMP9/GDF2 Mesenchymal stem cells(MSCs) METABOLISM OSTEOGENESIS Regenerative medicine TUMORIGENESIS
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Wnt and BMP signaling crosstalk in regulating dental stem cells:Implications in dental tissue engineering 被引量:19
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作者 Fugui Zhang Jinlin Song +19 位作者 Hongmei Zhang Enyi Huang Dongzhe Song Viktor Tollemar Jing Wang Jinhua Wang Maryam Mohammed Qiang Wei jiaming fan Junyi Liao Yulong Zou Feng Liu Xue Hu Xiangyang Qu Liqun Chen Xinyi Yu Hue H.Luu Michael J.Lee Tong-Chuan He Ping Ji 《Genes & Diseases》 SCIE 2016年第4期263-276,共14页
Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues ma... Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade. 展开更多
关键词 BMP signaling Dental stem cells Oral stem cells Regenerative dentistry Signal transduction Tissue engineering Wnt signaling
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Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism 被引量:14
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作者 Wei Liu Zhongliang Deng +25 位作者 Zongyue Zeng jiaming fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou 《Genes & Diseases》 SCIE 2020年第2期235-244,共10页
Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in ... Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood. 展开更多
关键词 BMP9/GDF2 Bone morphogenetic proteins(BMPs) Hepatic metabolism Mesenchymal stem cells NEUROGENESIS Osteogenic differentiation Pulmonary arterial hypertension TUMORIGENESIS
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Ferroptosis as a novel form of regulated cell death:Implications in the pathogenesis,oncometabolism and treatment of human cancer 被引量:7
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作者 Feifei Pu Fengxia Chen +21 位作者 Zhicai Zhang Deyao Shi Binlong Zhong Xiao Lv Andrew Blake Tucker jiaming fan Alexander J.Li Kevin Qin Daniel Hu Connie Chen Hao Wang fang He Na Ni Linjuan Huang Qing Liu William Wagstaff Hue H.Luu Rex C.Haydon Le Shen Tong-Chuan He Jianxiang Liu Zengwu Shao 《Genes & Diseases》 SCIE 2022年第2期347-357,共11页
The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy.Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells.Anti-tumor drugs w... The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy.Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells.Anti-tumor drugs were developed to induce apoptosis,but some patient’s show apoptosis escape and chemotherapy resistance.Therefore,other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment.Ferroptosis is a newly discovered iron-dependent,non-apoptotic type of cell death that is highly negatively correlated with cancer development.Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis.This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment. 展开更多
关键词 Cancer Cancer therapy Clinical application Ferroptosis Lipid peroxidation PATHOGENESIS
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Thermal conductivity and mechanical properties of high density polyethylene composites filled with silicon carbide whiskers modified by cross-linked poly (vinyl alcohol) 被引量:5
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作者 jiaming fan Shiai Xu 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2018年第12期2407-2414,共8页
A thin layer of poly(vinyl alcohol)(PVA) was coated on the surface of silicon carbide whiskers(SCWs)and crosslinked by glutaraldehyde, and then these modified whiskers(mSCWs) were incorporated into high density polyet... A thin layer of poly(vinyl alcohol)(PVA) was coated on the surface of silicon carbide whiskers(SCWs)and crosslinked by glutaraldehyde, and then these modified whiskers(mSCWs) were incorporated into high density polyethylene(HDPE) to prepare HDPE/mSCW composites with a high thermal conductivity.The thermal conductivity, mechanical properties, heat resistance, thermal stability and morphology of HDPE/mSCW and HDPE/SCW composites were characterized and compared. The results reveal that the thermal conductivity of both HDPE/SCW and HDPE/mSCW composites increases with the increase of filler loading, and reaches a maximum of 1.48 and 1.69 W/(m K) at 40 wt% filler loading, which is 251.20% and 300.75% higher than that of HDPE, respectively. Significantly, HDPE/mSCW composites have a higher thermal conductivity than their HDPE/SCW counterparts with the same filler loading. In addition, the heat resistance, Young’s modulus and yield strength of both HDPE/SCW and HDPE/mSCW composites are also improved compared with that of HDPE. mSCW can be homogenously dispersed in the HDPE matrix, which contributes to the formation of thermally conductive networks by the inter-connection of mSCWs. 展开更多
关键词 Polyethylene composites Silicon carbide WHISKER Thermal conductivity
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Argonaute(AGO)proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells(MSCs) 被引量:4
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作者 Yukun Mao Na Ni +19 位作者 Linjuan Huang jiaming fan Hao Wang fang He Qing Liu Deyao Shi Kai Fu Mikhail Pakvasa William Wagstaff Andrew Blake Tucker Connie Chen Russell R.Reid Rex C.Haydon Sherwin H.Ho Michael J.Lee Tong-Chuan He Jian Yang Le Shen Lin Cai Hue H.Luu 《Genes & Diseases》 SCIE 2021年第6期918-930,共13页
As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the m... As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs.However,the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood.Emerging evidence indicates that noncoding RNAs,especially microRNAs,may play important roles in regulating MSC differentiation and bone formation.As highly conserved RNA binding proteins,Argonaute(AGO)proteins are essential components of the multi-protein RNA-induced silencing complexes(RISCs),which are critical for small RNA biogenesis.Here,we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs.We first found that BMP9 upregulated the expression of Ago1,Ago2 and Ago3 in MSCs.By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes,we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase(ALP)activity in MSCs.Furthermore,we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization,and ectopic bone formation.Collectively,our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs. 展开更多
关键词 Argonaute(AGO)proteins BMP9 Bone formation Lineage-specific differentiation Mesenchymal stem cells miRNA biogenesis Osteogenic signaling
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Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering 被引量:2
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作者 Jiamin Zhong Hao Wang +20 位作者 Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi Connie Chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo Guillermo A.Ameer Le Shen Tong-Chuan He jiaming fan 《Bioactive Materials》 SCIE 2022年第3期523-540,共18页
Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.A... Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration. 展开更多
关键词 KERATINOCYTES Skin tissue engineering Reversible immortalization SV40 large T antigen PPCN Skin wound healing
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Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway 被引量:2
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作者 Liqin An Qiong Shi +10 位作者 Ying Zhu Hao Wang Qi Peng Jinghong Wu Yu Cheng Wei Zhang Yanyu Yi Zihao Bao Hui Zhang Yetao Luo jiaming fan 《Genes & Diseases》 SCIE 2021年第4期531-544,共14页
Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previo... Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly inhibits hepatic steatosis and lowers serum triglycerides,playing a protective role against the progression of non-alcoholic fatty liver disease(NAFLD).However,the direct impact of BMP4 on hepatic glucose metabolism is poorly understood.Here,we investigated the regulatory roles of BMP4 in hepatic glucose metabolism.Through a comprehensive analysis of the 14 types of BMPs,we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation,reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism.Mechanistically,we demonstrated that BMP4 reduced the hepatic glucose lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.Collectively,our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism.This knowledge should aid us to understand the molecular pathogenesis of NAFLD,and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism. 展开更多
关键词 BMP4 Glucose metabolism Glycogen accumulation mTORC2 signaling Non-alcoholic fatty liver disease(NAFLD)
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