Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and in...Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.展开更多
Ankylosing spondylitis(AS)is a chronic,progressive,systemic autoimmune disease characterised by spinal stiffness and ocular,cardiac,intestinal,and peripheral joint involvements.Genetics,infectious agents,and immune-me...Ankylosing spondylitis(AS)is a chronic,progressive,systemic autoimmune disease characterised by spinal stiffness and ocular,cardiac,intestinal,and peripheral joint involvements.Genetics,infectious agents,and immune-mediated inflammatory processes have all been hypothesized to contribute to AS pathogenesis,but the precise aetiology remains elusive.Recent studies have identified biological and cellular factors that correlate with the onset and progression of AS.This has provided avenues of research that may help elucidate disease mechanisms and lead to advances in therapeutic interventions.This study aimed to examine some of the findings from recent molecular studies,focusing on the molecular mechanism and associated factors such as interleukin-17,tumor necrosis factor-alpha,receptor activator of nuclear factor-kappa B/receptor activator of nuclear factor-kappa B ligand/osteoprotegerin pathway,and related micro-RNAs to gain insight into aberrant bone formation in AS and potential approaches to its prevention.This editorial also addresses the contribution of osteoclasts to bone pathology in AS.The author examined the molecular pathways governing osteoclast differentiation and activity,with particular emphasis on relevant cytokines and immune cell interactions.A comprehensive understanding of these mechanisms is essential for the development of targeted therapies to mitigate excessive bone resorption and pathological skeletal remodeling in AS.展开更多
Soft(flexible and stretchable) biosensors have great potential in real-time and continuous health monitoring of various physiological factors, mainly due to their better conformability to soft human tissues and organs...Soft(flexible and stretchable) biosensors have great potential in real-time and continuous health monitoring of various physiological factors, mainly due to their better conformability to soft human tissues and organs, which maximizes data fidelity and minimizes biological interference.Most of the early soft sensors focused on sensing physical signals. Recently, it is becoming a trend that novel soft sensors are developed to sense and monitor biochemical signals in situ in real biological environments, thus providing much more meaningful data for studying fundamental biology and diagnosing diverse health conditions. This is essential to decentralize the healthcare resources towards predictive medicine and better disease management. To meet the requirements of mechanical softness and complex biosensing, unconventional materials, and manufacturing process are demanded in developing biosensors. In this review, we summarize the fundamental approaches and the latest and representative design and fabrication to engineer soft electronics(flexible and stretchable) for wearable and implantable biochemical sensing. We will review the rational design and ingenious integration of stretchable materials, structures, and signal transducers in different application scenarios to fabricate high-performance soft biosensors. Focus is also given to how these novel biosensors can be integrated into diverse important physiological environments and scenarios in situ, such as sweat analysis, wound monitoring, and neurochemical sensing. We also rethink and discuss the current limitations,challenges, and prospects of soft biosensors. This review holds significant importance for researchers and engineers, as it assists in comprehending the overarching trends and pivotal issues within the realm of designing and manufacturing soft electronics for biochemical sensing.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)are promising candidates for regenerative therapy due to their self-renewal capability,multilineage differentiation potential,and immunomodulatory effects.The molecular character...BACKGROUND Mesenchymal stem cells(MSCs)are promising candidates for regenerative therapy due to their self-renewal capability,multilineage differentiation potential,and immunomodulatory effects.The molecular characteristics of MSCs are influenced by their location.Recently,epidural fat(EF)and EF-derived MSCs(EF-MSCs)have garnered attention due to their potential benefits to the spinal microenvironment and their high expression of neural SC markers.However,their clinical applications are limited due to cell senescence and limited accessibility of EF.Although many studies have attempted to establish an immortalized,stable SC line,the characteristics of immortalized EF-MSCs remain to be clarified.AIM To establish and analyze stable immortalized EF-MSCs.METHODS The phenotypes of EF-MSCs were analyzed using optical microscopy.Cell immortalization was performed using lentiviral vectors.The biomolecular characteristics of the cells were analyzed by immunoblotting,quantitative PCR,and proteomics.RESULTS The immortalized EF-MSCs demonstrated a significantly extended lifespan compared to the control group,with well-preserved adipogenic potential and SC surface marker expression.Introduction of human telomerase reverse transcriptase genes markedly increased the lifespan of EF-MSCs.Proteomics analysis revealed substantial increase in the expression of DNA replication pathway components in immortalized EF-MSCs.CONCLUSION Immortalized EF-MSCs exhibited significantly enhanced proliferative capacity,retained adipogenic potential,and upregulated the expression of DNA replication pathway components.展开更多
Composite biomaterials comprising polylactide(PLA)and hydroxyapatite(HA)are applied in bone,cartilage and dental regenerative medicine,where HA confers osteoconductive properties.However,after surgical implantation,ad...Composite biomaterials comprising polylactide(PLA)and hydroxyapatite(HA)are applied in bone,cartilage and dental regenerative medicine,where HA confers osteoconductive properties.However,after surgical implantation,adverse immune responses to these composites can occur,which have been attributed to size and morphology of HA particles.Approaches to effectively modulate these adverse immune responses have not been described.PLA degradation products have been shown to alter immune cell metabolism(immunometabolism),which drives the inflammatory response.Accordingly,to modulate the inflammatory response to composite biomaterials,inhibitors were incorporated into composites comprised of amorphous PLA(aPLA)and HA(aPLA+HA)to regulate glycolytic flux.Inhibition at specific steps in glycolysis reduced proinflammatory(CD86+CD206-)and increased pro-regenerative(CD206+)immune cell populations around implanted aPLA+HA.Notably,neutrophil and dendritic cell(DC)numbers along with proinflammatory monocyte and macrophage populations were decreased,and Arginase 1 expression among DCs was increased.Targeting immunometabolism to control the proinflammatory response to biomaterial composites,thereby creating a pro-regenerative microenvironment,is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis,which could lead to improved bone regeneration.展开更多
基金Supported by 2024 Yeungnam University Grant,No.224A480005.
文摘Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.
基金Supported by 2024 Yeungnam University Research Grant.
文摘Ankylosing spondylitis(AS)is a chronic,progressive,systemic autoimmune disease characterised by spinal stiffness and ocular,cardiac,intestinal,and peripheral joint involvements.Genetics,infectious agents,and immune-mediated inflammatory processes have all been hypothesized to contribute to AS pathogenesis,but the precise aetiology remains elusive.Recent studies have identified biological and cellular factors that correlate with the onset and progression of AS.This has provided avenues of research that may help elucidate disease mechanisms and lead to advances in therapeutic interventions.This study aimed to examine some of the findings from recent molecular studies,focusing on the molecular mechanism and associated factors such as interleukin-17,tumor necrosis factor-alpha,receptor activator of nuclear factor-kappa B/receptor activator of nuclear factor-kappa B ligand/osteoprotegerin pathway,and related micro-RNAs to gain insight into aberrant bone formation in AS and potential approaches to its prevention.This editorial also addresses the contribution of osteoclasts to bone pathology in AS.The author examined the molecular pathways governing osteoclast differentiation and activity,with particular emphasis on relevant cytokines and immune cell interactions.A comprehensive understanding of these mechanisms is essential for the development of targeted therapies to mitigate excessive bone resorption and pathological skeletal remodeling in AS.
基金support from the National Science Foundation under Award Nos. EFMA-2318057, ECCS-2339495, ECCS-2334134, ECCS-2216131, and CMMI-2323917。
文摘Soft(flexible and stretchable) biosensors have great potential in real-time and continuous health monitoring of various physiological factors, mainly due to their better conformability to soft human tissues and organs, which maximizes data fidelity and minimizes biological interference.Most of the early soft sensors focused on sensing physical signals. Recently, it is becoming a trend that novel soft sensors are developed to sense and monitor biochemical signals in situ in real biological environments, thus providing much more meaningful data for studying fundamental biology and diagnosing diverse health conditions. This is essential to decentralize the healthcare resources towards predictive medicine and better disease management. To meet the requirements of mechanical softness and complex biosensing, unconventional materials, and manufacturing process are demanded in developing biosensors. In this review, we summarize the fundamental approaches and the latest and representative design and fabrication to engineer soft electronics(flexible and stretchable) for wearable and implantable biochemical sensing. We will review the rational design and ingenious integration of stretchable materials, structures, and signal transducers in different application scenarios to fabricate high-performance soft biosensors. Focus is also given to how these novel biosensors can be integrated into diverse important physiological environments and scenarios in situ, such as sweat analysis, wound monitoring, and neurochemical sensing. We also rethink and discuss the current limitations,challenges, and prospects of soft biosensors. This review holds significant importance for researchers and engineers, as it assists in comprehending the overarching trends and pivotal issues within the realm of designing and manufacturing soft electronics for biochemical sensing.
文摘BACKGROUND Mesenchymal stem cells(MSCs)are promising candidates for regenerative therapy due to their self-renewal capability,multilineage differentiation potential,and immunomodulatory effects.The molecular characteristics of MSCs are influenced by their location.Recently,epidural fat(EF)and EF-derived MSCs(EF-MSCs)have garnered attention due to their potential benefits to the spinal microenvironment and their high expression of neural SC markers.However,their clinical applications are limited due to cell senescence and limited accessibility of EF.Although many studies have attempted to establish an immortalized,stable SC line,the characteristics of immortalized EF-MSCs remain to be clarified.AIM To establish and analyze stable immortalized EF-MSCs.METHODS The phenotypes of EF-MSCs were analyzed using optical microscopy.Cell immortalization was performed using lentiviral vectors.The biomolecular characteristics of the cells were analyzed by immunoblotting,quantitative PCR,and proteomics.RESULTS The immortalized EF-MSCs demonstrated a significantly extended lifespan compared to the control group,with well-preserved adipogenic potential and SC surface marker expression.Introduction of human telomerase reverse transcriptase genes markedly increased the lifespan of EF-MSCs.Proteomics analysis revealed substantial increase in the expression of DNA replication pathway components in immortalized EF-MSCs.CONCLUSION Immortalized EF-MSCs exhibited significantly enhanced proliferative capacity,retained adipogenic potential,and upregulated the expression of DNA replication pathway components.
基金Funding for this work was provided in part by the James and Kathleen Cornelius Endowment at MSU.The Mass Spectrometry core at MSU,especially A.J.Schilmiller and J.O’Keefe,helped to analyze releasates.
文摘Composite biomaterials comprising polylactide(PLA)and hydroxyapatite(HA)are applied in bone,cartilage and dental regenerative medicine,where HA confers osteoconductive properties.However,after surgical implantation,adverse immune responses to these composites can occur,which have been attributed to size and morphology of HA particles.Approaches to effectively modulate these adverse immune responses have not been described.PLA degradation products have been shown to alter immune cell metabolism(immunometabolism),which drives the inflammatory response.Accordingly,to modulate the inflammatory response to composite biomaterials,inhibitors were incorporated into composites comprised of amorphous PLA(aPLA)and HA(aPLA+HA)to regulate glycolytic flux.Inhibition at specific steps in glycolysis reduced proinflammatory(CD86+CD206-)and increased pro-regenerative(CD206+)immune cell populations around implanted aPLA+HA.Notably,neutrophil and dendritic cell(DC)numbers along with proinflammatory monocyte and macrophage populations were decreased,and Arginase 1 expression among DCs was increased.Targeting immunometabolism to control the proinflammatory response to biomaterial composites,thereby creating a pro-regenerative microenvironment,is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis,which could lead to improved bone regeneration.
