Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the ...Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC.Methods:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were confirmed by cell counting kit-8(CCK-8),colony forming,Transwell assays.And Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunofluorescence assays.Then nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)staining.Results:In our study,we proved that curcumin significantly inhibited the CRC cell viability,cell migration,and cell invasion abilities.In addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells.Further,in the nude mice model,curcumin treatment significantly decreased the size and weight of xenotransplant tumors.Conclusion:Therefore,curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.展开更多
Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells.Recent studies have revealed a close relationship between exosomes and bone homeostasis. It i...Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells.Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury.展开更多
Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease progression.Particularly,mitochondrial dysfunctions are identified in many common pa...Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease progression.Particularly,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and cancer.However,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases.Nonetheless,these complexities do not prevent mitochondria from being among the most important therapeutic targets.In recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials.Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various diseases.Mitochondrial components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries.Here,we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases.We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology agents.Finally,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.展开更多
As the crucial powerhouse for cell metabolism and tissue survival,the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands.In addition to intrac...As the crucial powerhouse for cell metabolism and tissue survival,the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands.In addition to intracellular changes,mitochondria can also be transferred intercellularly.Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction,the intercellular mitochondrial transfer also occurs under physiological conditions.In this review,the phenomenon of mitochondrial transfer is described according to its function under both physiological and pathological conditions,including tissue homeostasis,damaged tissue repair,tumor progression,and immunoregulation.Then,the mechanisms that contribute to this process are summarized,such as the trigger factors and transfer routes.Furthermore,various perspectives are explored to better understand the mysteries of cell-cell mitochondrial trafficking.In addition,potential therapeutic strategies for mitochondria-targeted application to rescue tissue damage and degeneration,as well as the inhibition of tumor progression,are discussed.展开更多
Biopolymers play a critical role as scaffolds used in tendon and ligament(TL)regeneration.Although advanced biopolymer materials have been proposed with optimised mechanical properties,biocompatibility,degradation,and...Biopolymers play a critical role as scaffolds used in tendon and ligament(TL)regeneration.Although advanced biopolymer materials have been proposed with optimised mechanical properties,biocompatibility,degradation,and processability,it is still challenging to find the right balance between these properties.Here,we aim to develop novel hybrid biocomposites based on poly(p-dioxanone)(PDO),poly(lactide-co-caprolactone)(LCL)and silk to produce high-performance grafts suitable for TL tissue repair.Biocomposites containing 1-15%of silk were studied through a range of characterisation techniques.We then explored biocompatibility through in vitro and in vivo studies using a mouse model.We found that adding up to 5%silk increases the tensile properties,degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the composites.Furthermore,addition of silk increases surface roughness and hydrophilicity.In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h,while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation.Finally,we selected a promising biocomposite and created a prototype TL graft based on extruded fibres.We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament(ACL)repair applications.展开更多
Tendon and ligament(TL)injuries affect millions of people annually.Biopolymers play a significant role in TL tissue repair,whether the treatment relies on tissue engineering strategies or using artificial tendon graft...Tendon and ligament(TL)injuries affect millions of people annually.Biopolymers play a significant role in TL tissue repair,whether the treatment relies on tissue engineering strategies or using artificial tendon grafts.The biopolymer governs the mechanical properties,biocompatibility,degradation,and fabrication method of the TL scaffold.Many natural,synthetic and hybrid biopolymers have been studied in TL regeneration,often combined with therapeutic agents and minerals to engineer novel scaffold systems.However,most of the advanced biopolymers have not advanced to clinical use yet.Here,we aim to review recent biopolymers and discuss their features for TL tissue engineering.After introducing the properties of the native tissue,we discuss different types of natural,synthetic and hybrid biopolymers used in TL tissue engineering.Then,we review biopolymers used in commercial absorbable and non-absorbable TL grafts.Finally,we explain the challenges and future directions for the development of novel biopolymers in TL regenerative treatment.展开更多
基金This work was financially supported by the Second Batch of Medical and Health Science and Technology Plan(self-financing)Projects in Shantou in 2020,Shantou Science and Technology Bureau Document Shantou([2020]No.58).
文摘Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC.Methods:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were confirmed by cell counting kit-8(CCK-8),colony forming,Transwell assays.And Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunofluorescence assays.Then nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)staining.Results:In our study,we proved that curcumin significantly inhibited the CRC cell viability,cell migration,and cell invasion abilities.In addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells.Further,in the nude mice model,curcumin treatment significantly decreased the size and weight of xenotransplant tumors.Conclusion:Therefore,curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.
基金the support from Perron Institute for Neurological and Translational Science, Department of Orthopaedics, The Second Affiliated HospitalYuying Children's Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, Shanghai Sixth People’s Hospital of Shanghai Jiaotong University
文摘Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells.Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury.
基金supported by the National Natural Science Foundation of China(82002339 to Junjie Gao)Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System(BJ1-9000-22-4002).
文摘Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease progression.Particularly,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and cancer.However,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases.Nonetheless,these complexities do not prevent mitochondria from being among the most important therapeutic targets.In recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials.Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various diseases.Mitochondrial components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries.Here,we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases.We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology agents.Finally,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.
基金supported by the grants from National Natural Science Foundation of China(Nos.81820108020 and 81672143)Shanghai Pujiang Program(No.2020PJD039)the fund from China Scholarship Council.
文摘As the crucial powerhouse for cell metabolism and tissue survival,the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands.In addition to intracellular changes,mitochondria can also be transferred intercellularly.Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction,the intercellular mitochondrial transfer also occurs under physiological conditions.In this review,the phenomenon of mitochondrial transfer is described according to its function under both physiological and pathological conditions,including tissue homeostasis,damaged tissue repair,tumor progression,and immunoregulation.Then,the mechanisms that contribute to this process are summarized,such as the trigger factors and transfer routes.Furthermore,various perspectives are explored to better understand the mysteries of cell-cell mitochondrial trafficking.In addition,potential therapeutic strategies for mitochondria-targeted application to rescue tissue damage and degeneration,as well as the inhibition of tumor progression,are discussed.
基金The authors also gratefully acknowledge funding from the Australian Research Council(IC170100061)through the Centre for Personalised Therapeutics Technologies,and the Science-Industry PhD Fellowship from the Western Australia Department of Jobs,Tourism,Science and Innovation(awarded to B.S.H.).
文摘Biopolymers play a critical role as scaffolds used in tendon and ligament(TL)regeneration.Although advanced biopolymer materials have been proposed with optimised mechanical properties,biocompatibility,degradation,and processability,it is still challenging to find the right balance between these properties.Here,we aim to develop novel hybrid biocomposites based on poly(p-dioxanone)(PDO),poly(lactide-co-caprolactone)(LCL)and silk to produce high-performance grafts suitable for TL tissue repair.Biocomposites containing 1-15%of silk were studied through a range of characterisation techniques.We then explored biocompatibility through in vitro and in vivo studies using a mouse model.We found that adding up to 5%silk increases the tensile properties,degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the composites.Furthermore,addition of silk increases surface roughness and hydrophilicity.In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h,while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation.Finally,we selected a promising biocomposite and created a prototype TL graft based on extruded fibres.We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament(ACL)repair applications.
基金supported by the Department of Jobs,Tourism,Science and Innovation(JTSI),Government of Western Australia,through the Science Industry PhD Fellowship Program.
文摘Tendon and ligament(TL)injuries affect millions of people annually.Biopolymers play a significant role in TL tissue repair,whether the treatment relies on tissue engineering strategies or using artificial tendon grafts.The biopolymer governs the mechanical properties,biocompatibility,degradation,and fabrication method of the TL scaffold.Many natural,synthetic and hybrid biopolymers have been studied in TL regeneration,often combined with therapeutic agents and minerals to engineer novel scaffold systems.However,most of the advanced biopolymers have not advanced to clinical use yet.Here,we aim to review recent biopolymers and discuss their features for TL tissue engineering.After introducing the properties of the native tissue,we discuss different types of natural,synthetic and hybrid biopolymers used in TL tissue engineering.Then,we review biopolymers used in commercial absorbable and non-absorbable TL grafts.Finally,we explain the challenges and future directions for the development of novel biopolymers in TL regenerative treatment.
