Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-...Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.展开更多
Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was perform...Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers.展开更多
Intracellular cAMP and Ca^2+ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone (LH) and human ehorionic gonadotropin (hCG). However, the i...Intracellular cAMP and Ca^2+ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone (LH) and human ehorionic gonadotropin (hCG). However, the identification of Ca^2+ entry implicated in Leydig cell steroidogenesis is not well defined. The objective of this study was to identify the type of Ca^2+ channel that affects Leydig cell steroidogenesis. In vitro steroidogenesis in the freshly dissociated Leydig cells of mice was induced by hCG incubation. The effects of mibefradil (a putative T-type Ca^2+ channel blocker) on steroidogenesis were assessed using reverse transcription (RT)-polymerase chain reaction analysis for the steroidogenic acute regulatory protein (STAR) mRNA expression and testosterone production using radioimmunoassay. In the presence of 1.0 mmol L-1 extracellular Ca^2+, hCG at 1 to 100 IU noticeably elevated both StAR mRNA level and testosterone secretion (P 〈 0.05), and the stimulatory effects of hCG were markedly diminished by mibefradil in a dose-dependent manner (P 〈 0.05). Moreover; the hCG-induced increase in testosterone production was completely removed when external Ca^2+ was omitted, implying that Ca entry is needed for hCG-induced steroidogenesis. Furthermore, a patch-clamp study revealed the presence of mibefradil-sensitive Ca^24- currents seen at a concentration range that nearly paralleled those inhibiting steroidogenesis. Collectively, Our data provide evidence that hCG-stimulated steroidogenesis is mediated at least in part by Ca^2+ entry carried out by the T-type Ca^2+ channel in the Leydig cells of mice.展开更多
Dental pulp is composed of nerves,blood vessels,and various types of cells and surrounded by a thick and hard enamel-dentin matrix.Due to its importance in the maintenance of tooth vitality,there have been intensive e...Dental pulp is composed of nerves,blood vessels,and various types of cells and surrounded by a thick and hard enamel-dentin matrix.Due to its importance in the maintenance of tooth vitality,there have been intensive efforts to analyze the complex cellularlevel organization of the dental pulp in teeth.Although conventional histologic analysis has provided microscopic images of the dental pulp,3-dimensional (3D) cellular-level visualization of the whole dental pulp in an intact tooth has remained a technically challenging task.This is mainly due to the inevitable disruption and loss of microscopic structural features during the process of mechanical sectioning required for the preparation of the tooth sample for histological observation.To accomplish 3D microscopic observation of thick intact tissue,various optical clearing techniques have been developed mostly for soft tissue,and their application for hard tissues such as bone and teeth has only recently started to be investigated.In this work,we established a simple and rapid optical clearing technique for intact mouse teeth without the time-consuming process of decalcification.We achieved 3D cellular-level visualization of the microvasculature and various immune cell distributions in the whole dental pulp of mouse teeth under normal and pathologic conditions.This technique could be used to enable diverse research methods on tooth development and regeneration by providing 3D visualization of various pulpal cells in intact mouse teeth.展开更多
Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues.Although the prevalent treatment is the complete removal of the whole infected tissue,this leads to a loss of ...Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues.Although the prevalent treatment is the complete removal of the whole infected tissue,this leads to a loss of tissue function and serious complications.Herein the dental pulp infection,as one of the most common dental problems,was selected as a clinically relevant case to regenerate using a multifunctional nanotherapeutic approach.For this,a mesoporous bioactive glass nano-delivery system incorporating silicate,calcium,and copper as well as loading epidermal growth factor(EGF)was designed to provide antibacterial/pro-angiogenic and osteo/odontogenic multiple therapeutic effects.Amine-functionalized Cu-doped bioactive glass nanospheres(Cu-BGn)were prepared to be 50–60 nm in size,mesoporous,positive-charged and bone-bioactive.The Cu-BGn could release bioactive ions(copper,calcium and silicate ions)with therapeutically-effective doses.The Cu-BGn treatment to human umbilical vein endothelial cells(HUVEC)led to significant enhancement of the migration,tubule formation and expression of angiogenic gene(e.g.vascular endothelial growth factor,VEGF).Furthermore,the EGF-loaded Cu-BGn(EGF@Cu-BGn)showed pro-angiogenic effects with antibacterial activity against E.faecalis,a pathogen commonly involved in the pulp infection.Of note,under the co-culture condition of HUVEC with E.faecalis,the secretion of VEGF was up-regulated.In addition,the osteo/odontogenic stimulation of the EGF@Cu-BGn was evidenced with human dental pulp stem cells.The local administration of the EGF@Cu-BGn in a rat molar tooth defect infected with E.faecalis revealed significant in vivo regenerative capacity,highlighting the nanotherapeutic uses of the multifunctional nanoparticles for regenerating infected/damaged hard tissues.展开更多
The exfoliation of bulk graphitic carbon nitride(g-C_(3)N_(4))into monolayer has been intensively studied to induce maximum sur-face area for fundamental studies,but ended in failure to realize chemi-cally and physica...The exfoliation of bulk graphitic carbon nitride(g-C_(3)N_(4))into monolayer has been intensively studied to induce maximum sur-face area for fundamental studies,but ended in failure to realize chemi-cally and physically well-defined monolayer of g-C_(3)N_(4)mostly due to the difficulty in reducing the layer thickness down to an atomic level.It has,therefore,remained as a challenging issue in two-dimensional(2D)chemistry and physics communities.In this study,an“atomic monolayer of g-C_(3)N_(4)with perfect two-dimensional limit”was successfully prepared by the chemically well-defined two-step routes.The atomically resolved monolayer of g-C_(3)N_(4)was also confirmed by spectroscopic and micro-scopic analyses.In addition,the experimental Cs-HRTEM image was collected,for the first time,which was in excellent agreement with the theoretically simulated;the evidence of monolayer of g-C_(3)N_(4)in the perfect 2D limit becomes now clear from the HRTEM image of orderly hexagonal symmetry with a cavity formed by encirclement of three adjacent heptazine units.Compared to bulk g-C_(3)N_(4),the present g-C_(3)N_(4)monolayer showed significantly higher photocatalytic gen-eration of H2O2 and H2,and electrocatalytic oxygen reduction reaction.In addition,its photocatalytic efficiency for H2O2 production was found to be the best for any known g-C_(3)N_(4)nanomaterials,underscoring the remarkable advantage of monolayer formation in optimizing the catalyst performance of g-C_(3)N_(4).展开更多
Rigidity(or stiffness)of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors,such as contractility,motility,and sp...Rigidity(or stiffness)of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors,such as contractility,motility,and spreading,and the resultant pathophysiological phenomena.Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events,including migration,lineage specification,and mechanical memory.Moreover,the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control,tissue repair,and disease progression.Thus,here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors,with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems,further discussion of the events and considerations in tissue-mimicking 3D conditions,and then examination of the in vivo findings that concern material/matrix rigidity.The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.展开更多
Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells.Among others,methacrylated gelatin(GelMA)has become a representative hydrogel for...Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells.Among others,methacrylated gelatin(GelMA)has become a representative hydrogel formulation,finding various biomedical applications.Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials,aiming to provide enhanced physicochemical and biological properties to GelMA.The benefits of this approach are multiple:i)reinforcing mechanical properties,ii)modulating viscoelastic property to allow 3D printability of bio-inks,iii)rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues(e.g.,muscle,nerve),iv)providing stimuli-responsiveness to actively deliver therapeutic molecules,and v)endowing therapeutic capacity in tissue repair process(e.g.,antioxidant effects).The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues(bone,skin,cardiac,and nerve)that are rarely observable with GelMA.Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics.The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.展开更多
All-in-one treatments represent a paradigm shift in future medicine.For example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intes...All-in-one treatments represent a paradigm shift in future medicine.For example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels.Furthermore,molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy.This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component.These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy.Next,peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions,specifically by nanomicelles.The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation.Hence,the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5(TLR5)as the main target of flagellin binding and Notch-1.The peptide binding potently suppressed inflammatory signaling without drug loading,where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha.The results were produced using a human colorectal cell line,clinical IBD patient cells,gut-on-a-chip,a mouse IBD model,and pig experiments to validate the translational utility.展开更多
We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical prop...We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells,long duration of T cell tethering,and DC-specific co-stimulatory cues.The DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands,anti-CD3(αCD3)and anti-CD28(αCD28)antibodies,followed by adsorption of releasable interleukin-2(IL-2).The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in vivo.We demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared toαCD3/αCD28-func-tionalized Dynabead.More importantly,major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing ability.In addition,most of the expanded T cells(~97%)can be harvested from the scaffold by density gradient centri-fugation.Overall,the DC-mimicking scaffold offers a scalable,modular,and customizable platform for rapid expansion of highly functional T cells for ACT.展开更多
The recent article published in Signal Transduction and Targeted Therapy sheds light on the significance of N6-methyladenosine(m6A)methyltransferase-like protein METTL14 in mitigating the progression of metabolic dysf...The recent article published in Signal Transduction and Targeted Therapy sheds light on the significance of N6-methyladenosine(m6A)methyltransferase-like protein METTL14 in mitigating the progression of metabolic dysfunction-associated fatty liver disease(MAFLD).1 In this study,Wang et al.elucidated the downregulation of METTL14 in hepatocytes from both MAFLD patients and high-fat diet(HFD)-induced MAFLD mouse models,underscoring its pivotal role in maintaining hepatic lipid and redox homeostasis in normal livers.展开更多
基金supported by the grants from National Research Foundation(NRF,#2021R1A5A2022318,#RS-2023-00220408,#RS-2023-00247485),Republic of Korea.
文摘Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.
基金supported by Dankook University Research Grant (2011)
文摘Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers.
文摘Intracellular cAMP and Ca^2+ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone (LH) and human ehorionic gonadotropin (hCG). However, the identification of Ca^2+ entry implicated in Leydig cell steroidogenesis is not well defined. The objective of this study was to identify the type of Ca^2+ channel that affects Leydig cell steroidogenesis. In vitro steroidogenesis in the freshly dissociated Leydig cells of mice was induced by hCG incubation. The effects of mibefradil (a putative T-type Ca^2+ channel blocker) on steroidogenesis were assessed using reverse transcription (RT)-polymerase chain reaction analysis for the steroidogenic acute regulatory protein (STAR) mRNA expression and testosterone production using radioimmunoassay. In the presence of 1.0 mmol L-1 extracellular Ca^2+, hCG at 1 to 100 IU noticeably elevated both StAR mRNA level and testosterone secretion (P 〈 0.05), and the stimulatory effects of hCG were markedly diminished by mibefradil in a dose-dependent manner (P 〈 0.05). Moreover; the hCG-induced increase in testosterone production was completely removed when external Ca^2+ was omitted, implying that Ca entry is needed for hCG-induced steroidogenesis. Furthermore, a patch-clamp study revealed the presence of mibefradil-sensitive Ca^24- currents seen at a concentration range that nearly paralleled those inhibiting steroidogenesis. Collectively, Our data provide evidence that hCG-stimulated steroidogenesis is mediated at least in part by Ca^2+ entry carried out by the T-type Ca^2+ channel in the Leydig cells of mice.
基金supported by the Basic Research Program (NRF-2017R1E1A1A01074190)the Bio & Medical Technology Development Program (NRF-2017M3A9E4047243) of the National Research Foundation of Korea funded by the Ministry of Science and ICT, Republic of Korea
文摘Dental pulp is composed of nerves,blood vessels,and various types of cells and surrounded by a thick and hard enamel-dentin matrix.Due to its importance in the maintenance of tooth vitality,there have been intensive efforts to analyze the complex cellularlevel organization of the dental pulp in teeth.Although conventional histologic analysis has provided microscopic images of the dental pulp,3-dimensional (3D) cellular-level visualization of the whole dental pulp in an intact tooth has remained a technically challenging task.This is mainly due to the inevitable disruption and loss of microscopic structural features during the process of mechanical sectioning required for the preparation of the tooth sample for histological observation.To accomplish 3D microscopic observation of thick intact tissue,various optical clearing techniques have been developed mostly for soft tissue,and their application for hard tissues such as bone and teeth has only recently started to be investigated.In this work,we established a simple and rapid optical clearing technique for intact mouse teeth without the time-consuming process of decalcification.We achieved 3D cellular-level visualization of the microvasculature and various immune cell distributions in the whole dental pulp of mouse teeth under normal and pathologic conditions.This technique could be used to enable diverse research methods on tooth development and regeneration by providing 3D visualization of various pulpal cells in intact mouse teeth.
基金a National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(2019R1C1C1002490,2018R1A2B3003446)by the Global Research Development Center Program(2018K1A4A3A01064257)by the Priority Research Center Program provided by the Ministry of Education(2019R1A6A1A11034536)。
文摘Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues.Although the prevalent treatment is the complete removal of the whole infected tissue,this leads to a loss of tissue function and serious complications.Herein the dental pulp infection,as one of the most common dental problems,was selected as a clinically relevant case to regenerate using a multifunctional nanotherapeutic approach.For this,a mesoporous bioactive glass nano-delivery system incorporating silicate,calcium,and copper as well as loading epidermal growth factor(EGF)was designed to provide antibacterial/pro-angiogenic and osteo/odontogenic multiple therapeutic effects.Amine-functionalized Cu-doped bioactive glass nanospheres(Cu-BGn)were prepared to be 50–60 nm in size,mesoporous,positive-charged and bone-bioactive.The Cu-BGn could release bioactive ions(copper,calcium and silicate ions)with therapeutically-effective doses.The Cu-BGn treatment to human umbilical vein endothelial cells(HUVEC)led to significant enhancement of the migration,tubule formation and expression of angiogenic gene(e.g.vascular endothelial growth factor,VEGF).Furthermore,the EGF-loaded Cu-BGn(EGF@Cu-BGn)showed pro-angiogenic effects with antibacterial activity against E.faecalis,a pathogen commonly involved in the pulp infection.Of note,under the co-culture condition of HUVEC with E.faecalis,the secretion of VEGF was up-regulated.In addition,the osteo/odontogenic stimulation of the EGF@Cu-BGn was evidenced with human dental pulp stem cells.The local administration of the EGF@Cu-BGn in a rat molar tooth defect infected with E.faecalis revealed significant in vivo regenerative capacity,highlighting the nanotherapeutic uses of the multifunctional nanoparticles for regenerating infected/damaged hard tissues.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.2020R1I1A1A01072161)and under the framework of the International Cooperation Program managed by NRF(No.2017K2A9A2A10013104)supported by the NRF grant funded by the Korea government(MSIP)(No.NRF-2020R1A2C3008671).
文摘The exfoliation of bulk graphitic carbon nitride(g-C_(3)N_(4))into monolayer has been intensively studied to induce maximum sur-face area for fundamental studies,but ended in failure to realize chemi-cally and physically well-defined monolayer of g-C_(3)N_(4)mostly due to the difficulty in reducing the layer thickness down to an atomic level.It has,therefore,remained as a challenging issue in two-dimensional(2D)chemistry and physics communities.In this study,an“atomic monolayer of g-C_(3)N_(4)with perfect two-dimensional limit”was successfully prepared by the chemically well-defined two-step routes.The atomically resolved monolayer of g-C_(3)N_(4)was also confirmed by spectroscopic and micro-scopic analyses.In addition,the experimental Cs-HRTEM image was collected,for the first time,which was in excellent agreement with the theoretically simulated;the evidence of monolayer of g-C_(3)N_(4)in the perfect 2D limit becomes now clear from the HRTEM image of orderly hexagonal symmetry with a cavity formed by encirclement of three adjacent heptazine units.Compared to bulk g-C_(3)N_(4),the present g-C_(3)N_(4)monolayer showed significantly higher photocatalytic gen-eration of H2O2 and H2,and electrocatalytic oxygen reduction reaction.In addition,its photocatalytic efficiency for H2O2 production was found to be the best for any known g-C_(3)N_(4)nanomaterials,underscoring the remarkable advantage of monolayer formation in optimizing the catalyst performance of g-C_(3)N_(4).
基金supported by the grants(2021R1A5A2022318,2019R1C1C1002490,2018R1A2B3003446,2018K1A4A3A01064257,2019R1A6A1A11034536),National Research Foundation,Republic of Korea.
文摘Rigidity(or stiffness)of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors,such as contractility,motility,and spreading,and the resultant pathophysiological phenomena.Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events,including migration,lineage specification,and mechanical memory.Moreover,the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control,tissue repair,and disease progression.Thus,here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors,with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems,further discussion of the events and considerations in tissue-mimicking 3D conditions,and then examination of the in vivo findings that concern material/matrix rigidity.The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.
基金supported by the grants(2015K1A1A2032163,2020R1I1A1A01071828,2018K1A4A3A01064257,2021R1A5A2022318,2018R1D1A1B07048020),National Research Foundation(NRF),Republic of Korea.
文摘Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells.Among others,methacrylated gelatin(GelMA)has become a representative hydrogel formulation,finding various biomedical applications.Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials,aiming to provide enhanced physicochemical and biological properties to GelMA.The benefits of this approach are multiple:i)reinforcing mechanical properties,ii)modulating viscoelastic property to allow 3D printability of bio-inks,iii)rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues(e.g.,muscle,nerve),iv)providing stimuli-responsiveness to actively deliver therapeutic molecules,and v)endowing therapeutic capacity in tissue repair process(e.g.,antioxidant effects).The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues(bone,skin,cardiac,and nerve)that are rarely observable with GelMA.Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics.The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.
文摘All-in-one treatments represent a paradigm shift in future medicine.For example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels.Furthermore,molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy.This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component.These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy.Next,peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions,specifically by nanomicelles.The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation.Hence,the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5(TLR5)as the main target of flagellin binding and Notch-1.The peptide binding potently suppressed inflammatory signaling without drug loading,where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha.The results were produced using a human colorectal cell line,clinical IBD patient cells,gut-on-a-chip,a mouse IBD model,and pig experiments to validate the translational utility.
基金School of Engineering and Applied Science of Columbia University and the National Research Foundation of Korea(2020R1F1A1072699,2018K1A4A3A01064257,and 2021R1A5A2022318)Dankook University(Priority Institute Support Program in 2021,Global Research Program).
文摘We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells,long duration of T cell tethering,and DC-specific co-stimulatory cues.The DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands,anti-CD3(αCD3)and anti-CD28(αCD28)antibodies,followed by adsorption of releasable interleukin-2(IL-2).The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in vivo.We demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared toαCD3/αCD28-func-tionalized Dynabead.More importantly,major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing ability.In addition,most of the expanded T cells(~97%)can be harvested from the scaffold by density gradient centri-fugation.Overall,the DC-mimicking scaffold offers a scalable,modular,and customizable platform for rapid expansion of highly functional T cells for ACT.
基金This study was supported by the National Research Foundation of Korea(grant number 2021R1C1C1003904 to J.H.)。
文摘The recent article published in Signal Transduction and Targeted Therapy sheds light on the significance of N6-methyladenosine(m6A)methyltransferase-like protein METTL14 in mitigating the progression of metabolic dysfunction-associated fatty liver disease(MAFLD).1 In this study,Wang et al.elucidated the downregulation of METTL14 in hepatocytes from both MAFLD patients and high-fat diet(HFD)-induced MAFLD mouse models,underscoring its pivotal role in maintaining hepatic lipid and redox homeostasis in normal livers.