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
Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functi...Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials’ physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration.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
Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated...Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo.Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression,inducing cancer cell apoptosis(intrinsic and extrinsic),enhancing autophagy,inducing cell cycle arrest,as well as inhibiting tumour angiogenesis,invasion and migration.The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper,and the prospective applications of chaetocin in cancer prevention and therapy are also discussed.Our review provides the theoretical basis for exploiting the clinical application of chaetocin in cancer treatment.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
Extensive in vitro and in vivo research reveals multiple intracellular molecular targets of Antrodia camphorata,and these targets affect growth,apoptosis,angiogenesis,invasion and metastasis of cells.These targets inc...Extensive in vitro and in vivo research reveals multiple intracellular molecular targets of Antrodia camphorata,and these targets affect growth,apoptosis,angiogenesis,invasion and metastasis of cells.These targets include tumor suppressor,cell cycle regulator,transcription factor,angiogenesis and metastasis factor,apoptosis and survival regulator,etc.Additionally,more and more attention has been paid to the molecular mechanism of A.camphorata on the regulation of tumor stem cells.Meanwhile,there is evidence that the immunoregulation of A.camphorata is enhanced,which may lead cell cycle arrest or apoptosis.In this paper,molecular mechanism of tumor cells and tumor stem cells regulated at multiple targets by A.camphorata in vitro and in vivo in the past decade is summarized.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
The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In orde...The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.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
Objective： In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was...Objective： In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods： Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups： the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society （ICRS） standard. Results： The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups （P〈0.05）. Conclusions： Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage.展开更多
Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where...Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.展开更多
The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or ...The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP.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
Stem cells,especially mesenchymal progenitors or mesenchymal stem cells(MSCs),possess an intrinsic property to form compact spheroid-like assemblies,a phenomenon known as cell aggregation.In recent years,a growing bod...Stem cells,especially mesenchymal progenitors or mesenchymal stem cells(MSCs),possess an intrinsic property to form compact spheroid-like assemblies,a phenomenon known as cell aggregation.In recent years,a growing body of researches have uncovered that this is a cross-species conserved developmental event essential for initiating organogenesis in a variety of organs.Moreover,the self-assembly property also contributes to the regenerative capacities of MSC aggregates in vivo with broad range of applications in tissue engineering.In this review,the principles of self-assembled mesenchymal aggregation and its involvement in physiological organogenesis,as well as the construction approaches of engineering MSC aggregates and its application for organ regeneration are discussed.The authors aim to provide a speculative overview of the current understanding and the recent findings of cell aggregation,from both the developmental and the engineering perspectives,and thus offer insights into the understanding of stem cell biology and the establishment of novel organ regeneration strategies.展开更多
Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeu...Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events.This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass(namely,CoNZ),which exhibits high enzymatic/catalytic activity while releasing therapeutic ions.Cobalt oxide“Co3O4”tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS.Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process,promoting neovascularization,matrix deposition,and epithelial lining while reducing pro-inflammatory signs.Notably,CoNZ was highly effective in treating pathological wounds(streptozotocin-induced diabetic wounds).Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events.In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ.CoNZ-promoted angiogenesis was attributed to the release of cobalt ions,as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α.Finally,we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine.Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound,indicating the potential of CoNZ as a novel drug-free therapeutic approach.展开更多
The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have ...The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication, articulation, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.展开更多
Background Transforming growth factor-β1 （TGF-β1） is known to have a role in keloid formation through the activation of fibroblasts and the acceleration of collagen deposition. The objective of this current study ...Background Transforming growth factor-β1 （TGF-β1） is known to have a role in keloid formation through the activation of fibroblasts and the acceleration of collagen deposition. The objective of this current study was to isolate TGF-β1 phage model peptides from a phage display 7-mer peptide library to evaluate their therapeutic effect on inhibiting the activity of keloid fibroblasts.Methods A phage display 7-mer peptide library was screened using monoclonal anti-human TGF-β1 as the target to obtain specific phages containing ectogenous model peptides similar to TGF-β1. Enzyme-linked immunosorbent assay （ELISA） was performed to select monoclonal phages with good binding activity, which underwent DNA sequencing. MTT assay and apoptosis assessment were used to evaluate the biological effects of the phage model peptides on keloid fibroblasts. Immunofluorescence assay was employed to show the binding affinity of the model peptides on phages causing keloid fibroblasts. Quantitative real-time PCR analysis was carried out to detect the expressions of nuclear factor κB （NF-κB） mRNA, connective tissue growth factor （CTGF） mRNA and TGF-β receptor Ⅱ （TβRII） mRNA in keloid fibroblasts.Results Specific phages with good results of ELISA were beneficiated. Four phage model peptides were obtained. The data of MTT showed that TGF-β1 and one phage model peptide （No. 4） could promote keloid fibroblasts proliferation,however, three phage model peptides （No. 1-3） could inhibit keloid fibroblasts proliferation. The results of apoptosis assessment showed that the three phage model peptides could slightly induce the apoptosis in keloid fibroblasts. The data of immunofluorescence assay revealed that the model peptides on phages rather than phages could bind to keloid fibroblasts. The findings of quantitative real-time PCR analysis suggested that the expressions of NF-κB mRNA and CTGF mRNA in the three phage model peptide groups decreased, while the expression of TβRII mRNA slightly increased.Conclusions Three phage model peptides isolated from a phage display 7-mer peptide library can inhibit keloid fibroblasts proliferation and induce the apoptosis in keloid fibroblasts. They can inhibit the activity of keloid fibroblasts by blocking TGF-β1 binding to its receptor and then regulating the expressions of NF-κB, CTGF and TβRII.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
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National Research Foundation of Korea(NRF,2021R1A5A2022318,2019R1A6A1A11034536,RS-2023-00220408,RS-2024-00334160,RS-2024-00348908)Ministry of Science and ICT and Ministry of Education.
文摘Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials’ physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration.
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Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo.Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression,inducing cancer cell apoptosis(intrinsic and extrinsic),enhancing autophagy,inducing cell cycle arrest,as well as inhibiting tumour angiogenesis,invasion and migration.The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper,and the prospective applications of chaetocin in cancer prevention and therapy are also discussed.Our review provides the theoretical basis for exploiting the clinical application of chaetocin in cancer treatment.
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Shandong Medical and Health Development Plan(2018WS423).
文摘Extensive in vitro and in vivo research reveals multiple intracellular molecular targets of Antrodia camphorata,and these targets affect growth,apoptosis,angiogenesis,invasion and metastasis of cells.These targets include tumor suppressor,cell cycle regulator,transcription factor,angiogenesis and metastasis factor,apoptosis and survival regulator,etc.Additionally,more and more attention has been paid to the molecular mechanism of A.camphorata on the regulation of tumor stem cells.Meanwhile,there is evidence that the immunoregulation of A.camphorata is enhanced,which may lead cell cycle arrest or apoptosis.In this paper,molecular mechanism of tumor cells and tumor stem cells regulated at multiple targets by A.camphorata in vitro and in vivo in the past decade is summarized.
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 grant from National High Technology Research and Development Program of China (863 Program) (2012AA020507)
文摘The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.
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.
基金supported by the National Natural Science Foundation of China(Nos.81171472,81201407,and 81071270)the Innovation Team Project of Sichuan Provincial Education Department(No.13TD0030)+1 种基金the Major Transformation Cultivation Project of Sichuan Provincial Education Department(No.15CZ0021)the Science and Technology Project of Nanchong City(No.14A0021),China
文摘Objective： In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods： Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups： the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society （ICRS） standard. Results： The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups （P〈0.05）. Conclusions： Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage.
基金financially supported by grants from the Nature Science Foundation of China (81620108007)National Key Research and Development Program of China (2016YFC1101400)+1 种基金Nature Science Foundation of China (31571532, 31601099)National Institutes of Health, Department of Health and Human Services (R01DE017449 to S.S.)
文摘Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.
基金funded by grants from the National Natural Science Foundation of China (Nos. 81620108007 and 81870768)the National Key Research and Development Program of China (Nos. 2016YFC1101400 and 2017YFA0104800)the Scientific Young Alma of Shaanxi province (2018KJXX-015)。
文摘The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP.
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National Key Research and Development Program of China,Grant/Award Number:2022YFA1104400National Natural Science Foundation of China,Grant/Award Numbers:81930025,82301028,82371020+1 种基金China Postdoctoral Science Foundation,Grant/Award Number:BX20230485Shaanxi Youth Science and Technology Rising Star Program,Grant/Award Number:2023KJXX-027。
文摘Stem cells,especially mesenchymal progenitors or mesenchymal stem cells(MSCs),possess an intrinsic property to form compact spheroid-like assemblies,a phenomenon known as cell aggregation.In recent years,a growing body of researches have uncovered that this is a cross-species conserved developmental event essential for initiating organogenesis in a variety of organs.Moreover,the self-assembly property also contributes to the regenerative capacities of MSC aggregates in vivo with broad range of applications in tissue engineering.In this review,the principles of self-assembled mesenchymal aggregation and its involvement in physiological organogenesis,as well as the construction approaches of engineering MSC aggregates and its application for organ regeneration are discussed.The authors aim to provide a speculative overview of the current understanding and the recent findings of cell aggregation,from both the developmental and the engineering perspectives,and thus offer insights into the understanding of stem cell biology and the establishment of novel organ regeneration strategies.
基金supported by the National Research Foundation of Korea(2021R1A5A2022318,2018K1A4A3A01064257,2019R1A6A1 A11034536,RS-2023-00220408,2022K1A3A1A08085419,2021R1I1 A1A01049104).
文摘Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events.This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass(namely,CoNZ),which exhibits high enzymatic/catalytic activity while releasing therapeutic ions.Cobalt oxide“Co3O4”tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS.Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process,promoting neovascularization,matrix deposition,and epithelial lining while reducing pro-inflammatory signs.Notably,CoNZ was highly effective in treating pathological wounds(streptozotocin-induced diabetic wounds).Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events.In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ.CoNZ-promoted angiogenesis was attributed to the release of cobalt ions,as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α.Finally,we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine.Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound,indicating the potential of CoNZ as a novel drug-free therapeutic approach.
基金the grants from the National Natural Science Foundation of China (Nos.31501121,31401255,81570976,and 31500786)Natural Science Foundation research project of Shaanxi Province (Nos.2016JQ8019 and 016KW-005).
文摘The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication, articulation, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.
基金This study was supported by grants from the Nationa1 Natura1 Science Foundation of China （No. 30670571, 30772258 and 81071560）, Science and Technology Research Program of Shandong Province （No. 2009GG10002078）, Scientific Research Development Plan of the Department of Education of Shandong Province （No. J07WD03） and National Basic Research Program of China （973 Program） （No. 2005CB522603）.
文摘Background Transforming growth factor-β1 （TGF-β1） is known to have a role in keloid formation through the activation of fibroblasts and the acceleration of collagen deposition. The objective of this current study was to isolate TGF-β1 phage model peptides from a phage display 7-mer peptide library to evaluate their therapeutic effect on inhibiting the activity of keloid fibroblasts.Methods A phage display 7-mer peptide library was screened using monoclonal anti-human TGF-β1 as the target to obtain specific phages containing ectogenous model peptides similar to TGF-β1. Enzyme-linked immunosorbent assay （ELISA） was performed to select monoclonal phages with good binding activity, which underwent DNA sequencing. MTT assay and apoptosis assessment were used to evaluate the biological effects of the phage model peptides on keloid fibroblasts. Immunofluorescence assay was employed to show the binding affinity of the model peptides on phages causing keloid fibroblasts. Quantitative real-time PCR analysis was carried out to detect the expressions of nuclear factor κB （NF-κB） mRNA, connective tissue growth factor （CTGF） mRNA and TGF-β receptor Ⅱ （TβRII） mRNA in keloid fibroblasts.Results Specific phages with good results of ELISA were beneficiated. Four phage model peptides were obtained. The data of MTT showed that TGF-β1 and one phage model peptide （No. 4） could promote keloid fibroblasts proliferation,however, three phage model peptides （No. 1-3） could inhibit keloid fibroblasts proliferation. The results of apoptosis assessment showed that the three phage model peptides could slightly induce the apoptosis in keloid fibroblasts. The data of immunofluorescence assay revealed that the model peptides on phages rather than phages could bind to keloid fibroblasts. The findings of quantitative real-time PCR analysis suggested that the expressions of NF-κB mRNA and CTGF mRNA in the three phage model peptide groups decreased, while the expression of TβRII mRNA slightly increased.Conclusions Three phage model peptides isolated from a phage display 7-mer peptide library can inhibit keloid fibroblasts proliferation and induce the apoptosis in keloid fibroblasts. They can inhibit the activity of keloid fibroblasts by blocking TGF-β1 binding to its receptor and then regulating the expressions of NF-κB, CTGF and TβRII.
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.
