RESUMO
Renal fibrosis compromises kidney function, and it is a risk factor for chronic kidney disease (CKD). CKD ultimately progresses to end-stage kidney disease that can be cured only by kidney transplantation. Owing to the increasing number of CKD patients, effective treatment strategies are urgently required for renal fibrosis. TGF-ß is a well-established fibrogenic factor that signals through SMAD2/3 signaling pathway. It was shown that there is a cross-talk between TGF-ß/SMAD and WNT/ß-catenin signaling pathways in renal tubular epithelial cells, and that a WNT/ß-catenin inhibitor, ICG-001, ameliorates TGF-ß1induced renal fibrosis. IC-2, a derivative of ICG-001, has been shown to potently induce hepatocyte differentiation of human mesenchymal stem cells by inhibiting WNT/ß-catenin signaling. In the present study, we examined the effect of ICG-001, IC-2, and IC-2 derivatives (IC-2-506-1, IC-2-506-2, IC-2-506-3, IC-2-Ar-Cl, IC-2-OH, IC-2-OTBS, and IC-2-F) on TGF-ß1-induced SMAD activation and fibrogenic response in immortalized human renal tubular epithelial HK-2 cells. All these compounds inhibited LiCl-induced WNT/ß-catenin reporter activation to a similar extent, whereas ICG-001, IC-2-OTBS, and IC-2-F almost completely suppressed TGF-ß1-induced SMAD reporter activation without apparent cytotoxicity. Phosphorylation of SMAD2/3 by TGF-ß1 was more potently inhibited by IC-2-OTBS and IC-2-F than by ICG-001 and IC-2. IC-2-F suppressed TGF-ß1-induced COL1A1 protein expression, whereas IC-2-506-1 and IC-2-OTBS suppressed TGF-ß1-induced epithelial-mesenchymal transition. These results demonstrated that IC-2 derivatives suppress the TGF-ß1-induced fibrogenic response of tubular epithelial cells and thus could be promising therapeutic agents for the treatment of renal fibrosis.
Assuntos
Células Epiteliais/efeitos dos fármacos , Nefropatias/prevenção & controle , Túbulos Renais/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose , Humanos , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , FosforilaçãoRESUMO
This study investigated the prophylactic effects of orally administered surface-deacetylated chitin nanofibers (SDACNFs) and chitosan against 5-fluorouracil (5-FU)-induced intestinal mucositis, which is a common side effect of 5-FU chemotherapy. SDACNFs and chitosan abolished histological abnormalities associated with intestinal mucositis and suppressed hypoproliferation and apoptosis of intestinal crypt cells. These results indicate that SDACNF and chitosan are useful agents for preventing mucositis induced by anti-cancer drugs.
Assuntos
Quitina/administração & dosagem , Quitina/uso terapêutico , Quitosana/uso terapêutico , Fluoruracila/efeitos adversos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Nanofibras/química , Acetilação , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Quitina/farmacologia , Quitosana/administração & dosagem , Quitosana/farmacologia , Feminino , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Camundongos Endogâmicos C57BL , Nanofibras/administração & dosagem , Nanofibras/ultraestrutura , Peroxidase/metabolismoRESUMO
We previously developed biobased wrinkled surfaces based on wood mimetic skins in which microscopic wrinkles were fabricated on a chitosan film by immersion in a phenolic acid solution, horseradish peroxidase-catalyzed surface reaction, and drying. Here, we prepared a diverse range of wrinkled films by immersion treatment at 30, 40, 50, and 60 °C in p-coumaric acid and then investigated the correlation between wrinkle morphology and mechanical properties. Wrinkle wavelengths gradually decreased as the immersion temperature increased as well as the previous report. In order to clarify the mechanisms responsible for the different wrinkle morphologies, the films were subjected to elastic moduli measurement and GPC analysis after immersion treatment. These experiments provided evidence that the chitosan around the film surface decomposed along with the immersion process. The decomposition was accelerated by higher immersion temperature, suggesting that higher temperatures led to the formation of softer skins, inducing smaller wrinkles. In fact, wrinkle morphologies with this system were predominately determined by the hardness of the wood mimetic skins. This phenomenon is consistent with the fundamentals of surface wrinkling in nature. This study is the first to demonstrate that artificial wrinkling triggered by water evaporation can be controlled by precise control of the surface hardness of soft material.
Assuntos
Materiais Biomiméticos , Dessecação , Fenômenos Mecânicos , Estresse Mecânico , Propriedades de Superfície , Temperatura , MadeiraRESUMO
A protein/CaCO3/chitin nanofiber complex was prepared from crab shells by a simple mechanical treatment with a high-pressure water-jet (HPWJ) system. The preparation process did not involve chemical treatments, such as removal of protein and calcium carbonate with sodium hydroxide and hydrochloric acid, respectively. Thus, it was economically and environmentally friendly. The nanofibers obtained had uniform width and dispersed homogeneously in water. Nanofibers were characterized in morphology, transparency, and viscosity. Results indicated that the shell was mostly disintegrated into nanofibers at above five cycles of the HPWJ system. The chemical structure of the nanofiber was maintained even after extensive mechanical treatments. Subsequently, the nanofiber complex was found to improve the growth of tomatoes in a hydroponics system, suggesting the mechanical treatments efficiently released minerals into the system. The homogeneous dispersion of the nanofiber complex enabled easier application as a fertilizer compared to the crab shell flakes.
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Exoesqueleto/química , Carbonato de Cálcio/química , Quitina/química , Nanofibras/química , Proteínas/química , Animais , Braquiúros/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/crescimento & desenvolvimento , Microscopia Eletrônica de Varredura , Nanofibras/toxicidade , Nanofibras/ultraestrutura , Desenvolvimento Vegetal/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse MecânicoRESUMO
Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young's modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young's modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials.
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Antifúngicos/química , Antifúngicos/farmacologia , Quitosana , Nanofibras , Quitina/química , Quitosana/química , Módulo de Elasticidade , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanofibras/química , Nanofibras/ultraestrutura , Resistência à TraçãoRESUMO
This study evaluated the effects of oral administration of surface-deacetylated chitin nanofibers (SDACNFs) on hypercholesterolemia using an experimental model. All rats were fed a high cholesterol diet with 1% w/w cholesterol and 0.5% w/w cholic acid for 28 days. Rats were divided equally into four groups: the control group was administered 0.05% acetic acid dissolved in tap water, and the SDACNF, chitosan (CS), and cellulose nanofiber (CLNF) groups were administered 0.1% CNF, CS, or CLNF dissolved in the tap water, respectively, during the experimental period. Changes in body weight, intake of food and water, and organ weight were measured. Serum blood chemistry and histopathological examination of the liver were performed. Administration of SDACNF did not affect body weight change, food and water intake, or organ weights. Administration of SDACNF and CS decreased the diet-induced increase in serum total cholesterol, chylomicron, very-low-density lipoprotein, and phospholipid levels on day 14. Moreover, oral administration of SDACNFs suppressed the increase of alanine transaminase levels on day 29 and suppressed vacuolar degeneration and accumulation of lipid droplets in liver tissue. These data indicate that SDACNF has potential as a functional food for patients with hypercholesterolemia.
Assuntos
Anticolesterolemiantes/administração & dosagem , Quitina/administração & dosagem , Hipercolesterolemia/dietoterapia , Nanofibras/administração & dosagem , Administração Oral , Animais , Anticolesterolemiantes/química , Celulose/administração & dosagem , Celulose/química , Quitina/química , Quitosana/administração & dosagem , Colesterol/sangue , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Lipoproteínas VLDL/sangue , Fosfolipídeos/sangue , RatosRESUMO
The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota.
Assuntos
Quitina/administração & dosagem , Microbioma Gastrointestinal , Metaboloma , Nanofibras/administração & dosagem , Administração Oral , Animais , Análise por Conglomerados , Metabolismo Energético , Fezes/química , Feminino , Redes e Vias Metabólicas , Metabolômica/métodos , CamundongosRESUMO
We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5-40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110-138 kDa) and high-molecular-weight fucoidan (HMWF: 300-330 kDa). The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet). The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Phaeophyceae/química , Polissacarídeos/farmacologia , Administração Oral , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias do Colo/prevenção & controle , Feminino , Marcação In Situ das Extremidades Cortadas , Células Matadoras Naturais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Polissacarídeos/administração & dosagem , BaçoRESUMO
Chitin nanofibers were acetylated to modify the fiber surface and were characterized in detail. The acetyl DS could be controlled from 0.99 to 2.96 by changing the reaction time. FT-IR spectra indicate that chitin nanofibers were acetylated completely after 50 min reaction time. X-ray diffraction profiles and TGA curves show that the chitin nanofibers were acetylated heterogeneously from the surface to the core. SEM images show that fiber shape was maintained even in the high-DS sample and that the thickness of the nanofibers increased with the introduction of bulky acetyl groups. Acetylated chitin nanofiber composites were fabricated with acrylic resin with the fiber content of approximately 25 wt %. Due to the size effect, all nanocomposites had high transparency, despite the variety of acetyl DS, and the transparency of the chitin nanofiber composite was less sensitive to acetylation. By only 1 min acetylation, the moisture absorption of the nanocomposite drastically decreased from 4.0 to 2.2%. Although the coefficient of thermal expansion (CTE) of the tricyclodecane dimethanol dimethacrylate (TCDDMA) resin was 6.4 x 10(-5) degrees C(-1), the CTE of the chitin nanofiber/TCDDMA composite decreased to 2.3 x 10(-5) degrees C(-1) by the reinforcement effect of the chitin nanofibers with low thermal expansion.
Assuntos
Quitina/química , Nanofibras , Acetilação , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
BACKGROUND: Liver fibrosis progresses to decompensated liver cirrhosis, for which medical needs remain unmet. We recently developed IC-2, a small-molecule compound that suppresses Wnt/ß-catenin signaling, and found that IC-2 also suppresses liver fibrosis. In this study, we performed three-step screening of newly synthesized IC-2 derivatives to identify other small-molecule compounds that suppress liver fibrosis. METHODS: The screening system consisted of three steps: a cell viability assay, a transcription factor 4 (TCF4) reporter assay, and induction of α-smooth muscle actin (α-SMA) and collagen 1α1 (Col1A1) expression in response to each compound. Screening using human LX-2 hepatic stellate cells (HSCs) was performed to target HSCs, which are the driver cells of liver fibrosis. RESULTS: In the first step, since 9b and 9b-CONH2 at 100 µM did not have any effects on cell viability, they were omitted in the next screening. Additionally, the conditions that led to > 40% inhibition of the controls were also excluded in subsequent screening. The second step was performed under 31 conditions for 19 small-molecule compounds. Sixteen small-molecule compounds caused significant reduction of TCF4 activity relative to that of 0.1% DMSO. Of the 16 compounds, the 10 showing the greatest suppression of TCF4 activity were selected for the third step. Expressions of mRNA for α-SMA and Col1A1 were significantly reduced by seven and three small-molecule compounds, respectively. The greatest reductions in the α-SMA and Col1A1 mRNA expressions were observed in the cells treated with IC-2-F. Protein expressions of α-SMA and Col1A1 caused by IC-2-F were also comparable to those caused by IC-2. CONCLUSION: IC-2-F was identified as a novel deactivating small-molecule compound for HSCs in vitro. These data suggest that IC-2-F is a promising medicine for liver fibrosis.
RESUMO
We have prepared silver nanoparticles on the surface of bacterial cellulose (BC) nanofibers. The synthesis of silver nanoparticles incorporates 2,2,6,6-tetramethylpiperidine-1-oxyradical (TEMPO)-mediated oxidation to introduce carboxylate groups on the surface of BC nanofibers. An ion exchange of the sodium to the silver salt was performed in AgNO(3) solution, followed by thermal reduction. By using oxidized BC nanofibers as a reaction template, we have prepared stable silver nanoparticles with a narrow size distribution and high density through strong ion interactions between host carboxylate groups and guest silver cations, which have been investigated by scanning electron microscopy, UV-visible spectroscopy, and a small-angle X-ray scattering method.
Assuntos
Celulose/química , Óxidos N-Cíclicos , Nanopartículas Metálicas/química , Prata/química , Bactérias/química , Ácidos Carboxílicos , Nanofibras/química , Eletricidade EstáticaRESUMO
Chitin nanofibers were prepared from dried crab shells by a simple grinding treatment in a never-dried state under an acidic condition after the removal of proteins and minerals. The obtained nanofibers were observed by FE-SEM and found to have a uniform width of approximately 10-20 nm and high aspect ratio; both these findings were similar to those for nanofibers from prawns. Furthermore, it was confirmed that the nanofibers were extracted from the natural chitin/protein/mineral composites of crab shell in their original state. That is, the N-acetyl group was not removed and the alpha-chitin crystal structure was maintained, as confirmed by elemental analysis data, FT-IR spectra, and X-ray diffraction profiles.
Assuntos
Quitina/química , Crustáceos , Nanoestruturas , Animais , Sequência de Carboidratos , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Chitosan-carboxymethyl dextran nanoparticles (CHI-CMD NPs) were prepared by the formation of polyelectrolyte complex via the interaction of the positive charged amino group of chitosan and the negative charged carboxyl group of carboxymethyl dextran. Biocompatible organic reagents such as lactic acid, phosphate-buffered saline, and carbonate-bicarbonate buffer were used to make CHI-CMD NPs. The pH value of narrowly distributive CHI-CMD NP suspension was close to the physiological value of 6.8, which made it possible for it to be directly applied in an in vitro test without further additional operations. In the presence of sugars (30 mM), the colloidal stability of CHI-CMD NPs could be extended to 5 to 7 days when the particle size could be maintained within a nanometer scale, while the addition of xylose or lactose was found to most effectively extend the colloidal stability of CHI-CMD NPs to 10 days. Scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis revealed that the structural integrity of CHI-CMD NPs was not destroyed after high steam pressure sterilization (121 degrees C, 30 min), which confirmed the autoclavable property of CHI-CMD NPs.
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Quitosana/síntese química , Dextranos/síntese química , Nanopartículas/química , Quitosana/química , Dextranos/química , Temperatura Alta , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Nanotecnologia/métodos , EsterilizaçãoRESUMO
We introduce a simple method for producing guanidinylation of chitosan (CS) with 1amidinopyrazole hydrochloride (AP). Production of GCS is proved via NMR, IR, and elemental analyses. In a reaction using 4.5â¯eq of AP for 7â¯days at room temperature, we obtained GCS with 42.3% of degree of guanidinylation (DG). The DG value can be controlled by the reaction time and AP amount. Furthermore, remarkable enhancement of the interaction between GCS and bovine serum albumin by guanidinylation was observed. This simple guanidinylation method for CS could provide novel additives for protein/peptide delivery systems.
Assuntos
Arginina/química , Peptídeos Penetradores de Células/química , Quitosana/química , Guanidina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Soroalbumina Bovina/químicaRESUMO
In order to synthesize a promising material for developing a novel peptide/protein delivery system, guanidinylation of chitooligosaccharides with 1-amidinopyrazole hydrochloride was investigated herein. The production of guanidinylated chitooligosaccharides was demonstrated by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and elemental analyses. Interestingly, we found that the reducing end in the guanidinylated chitooligosaccharides was converted to a cyclic guanidine structure (2-[(aminoiminomethyl)amino]-2-deoxy-d-glucose structure). This reaction was carefully proven by the guanidinylation of d-glucosamine. Although this is not the first report on the synthesis of the 2-[(aminoiminomethyl)amino]-2-deoxy-d-glucose, it has provided a rational synthetic route using the high reactivity of the reducing end. Furthermore, we found that the interaction between chitooligosaccharides and bovine serum albumin is weak when in a neutral pH environment; however, it is significantly improved by guanidinylation. The guanidinylated chitooligosaccharides are useful not only for the development of a novel drug delivery system but also as a chitinase/chitosanase inhibitor and an antibacterial agent.
Assuntos
Quitina/análogos & derivados , Guanidina/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Bovinos , Quitina/química , Quitina/metabolismo , Quitosana , Ciclização , Guanidina/química , Estrutura Molecular , Oligossacarídeos , Oxirredução , Ligação Proteica , Soroalbumina Bovina/químicaRESUMO
Chronic hepatitis viral infection, alcoholic intoxication, and obesity cause liver fibrosis, which progresses to decompensated liver cirrhosis, a disease for which medical demands cannot be met. Since there are currently no approved anti-fibrotic therapies for established liver fibrosis, the development of novel modalities is required to improve patient prognosis. In this study, we clarified the anti-fibrotic effects of cell sheets produced from human bone marrow-derived mesenchymal stem cells (MSCs) incubated on a temperature-sensitive culture dish with the chemical compound IC-2. Orthotopic transplantation of IC-2-engineered MSC sheets (IC-2 sheets) remarkably reduced liver fibrosis induced by chronic CCl4 administration. Further, the marked production of fibrolytic enzymes such as matrix metalloproteinase (MMP)-1 and MMP-14, as well as thioredoxin, which suppresses hepatic stellate cell activation, was observed in IC-2 sheets. Moreover, the anti-fibrotic effect of IC-2 sheets was much better than that of MSC sheets. Finally, knockdown experiments revealed that MMP-14 was primarily responsible for the reduction of liver fibrosis. Here, we show that IC-2 sheets could be a promising therapeutic option for established liver fibrosis.
Assuntos
Células da Medula Óssea/citologia , Inibidores Enzimáticos/farmacologia , Cirrose Hepática/terapia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Compostos Bicíclicos com Pontes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/terapia , Colágeno Tipo I/metabolismo , Hexaclorofeno/farmacologia , Humanos , Imuno-Histoquímica , Cirrose Hepática/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , TemperaturaRESUMO
In this study, the effects of chitosan and surface-deacetylated chitin nanofibrils (SDACNFs) on hair growth were evaluated. In human follicle dermal papilla cells in vitro, chitosan and SDACNFs were shown to increase cell growth on day 3 after the initiation of treatment, together with an increase in the production of fibroblast growth factor-7 (FGF-7) by these cells on day 3. Furthermore, in an in vivo study in mice, chitosan and SDACNF application promoted hair growth. The number of anagen follicles significantly increased compared with that in the control group, whereas the number of telogen follicles significantly decreased in the chitosan and SDACNF groups. In the chitosan and SDACNFs groups, moreover, the expression levels of FGF-7 and Sonic hedgehog were significantly upregulated in hair follicles. Overall, our results demonstrated that chitosan and SDACNFs promoted hair growth and therefore may have applications as novel therapeutic agents for the treatment of hair loss in patients.
Assuntos
Quitina/farmacologia , Quitosana/farmacologia , Cabelo/crescimento & desenvolvimento , Nanofibras/química , Acetilação , Animais , Proliferação de Células/efeitos dos fármacos , Cabelo/citologia , Cabelo/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Camundongos Endogâmicos C57BL , Propriedades de SuperfícieRESUMO
INTRODUCTION: We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/ß-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/ß-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs. METHODS: We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. The therapeutic potential of IC-2-induced hepatic cell sheets was assessed by transplantation of IC-2- and hexachlorophene-treated hepatic cell sheets using a mouse model of acute liver injury. RESULTS: Significant improvement of liver injury was elicited by the IC-2-treated hepatic cell sheets. The expression of complement C3 was enhanced by IC-2, followed by prominent hepatocyte proliferation stimulated through the activation of NF-κB and its downstream molecule STAT-3. Indeed, IC-2 also enhanced the expression of amphiregulin, resulting in the activation of the EGFR pathway and further stimulation of hepatocyte proliferation. As another important therapeutic mechanism, we revealed prominent reduction of oxidative stress mediated through upregulation of the thioredoxin (TRX) system by IC-2-treated hepatic cell sheets. The effects mediated by IC-2-treated sheets were superior compared with those mediated by hexachlorophene-treated sheets. CONCLUSION: The single compound IC-2 induced hepatic cell sheets that possess potent regeneration capacity and ameliorate acute liver injury.
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The Journal of Functional Biomaterials Editorial Office have been made aware that some parts of the article [1] are duplicated from other publications[...].
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We previously developed bio-based wrinkled surfaces induced by wood-mimetic skins upon drying in which microscopic wrinkles were fabricated on a chitosan (CS) film by immersing it in a phenolic acid solution, followed by horseradish peroxidase (HRP)-catalyzed surface reaction and drying. However, the detailed structure of the resulting wood-mimetic skins, including crosslinking mode and thickness, has not been clarified due to the difficulty of the analysis. Here, we prepare wrinkled films using ferulic acid (FE), vanillic acid (VA), and homovanillic acid (HO) and characterize their structures to clarify the unknown characteristics of wood-mimetic skin. Chemical and structural analyses of wood-mimetic skins prepared using VA and HO indicate that the crosslinking structure in the skin is composed of ionic bonds between CS and an oligophenolic residue generated by the HRP-catalyzed reaction on the CS surface. Moreover, the quantity of these ionic bonds is related to the skin hardness and wrinkle size. Finally, SEM and TOF-SIMS analyses indicate that the skin thickness is on the submicron order (<200nm).