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Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq enables time course monitoring of transcriptome changes, and with biotinylated individual TFs, it provides a multi-omics approach to understanding the mechanisms behind TF-mediated cell fate changes. Our iTF-seq study in mouse embryonic stem cells identified multiple TFs that trigger rapid transcriptome changes indicative of differentiation within a day of induction. Moreover, cells expressing these potent TFs often show a slower cell cycle and increased cell death. Further analysis using bioChIP-seq revealed that GCM1 and OTX2 act as pioneer factors and activators by increasing gene accessibility and activating the expression of lineage specification genes during cell fate conversion. iTF-seq has utility in both mapping cell fate conversion and understanding cell fate conversion mechanisms.
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Diferenciación Celular , Factores de Transcripción , Animales , Ratones , Diferenciación Celular/genética , Linaje de la Célula/genética , Perfilación de la Expresión Génica/métodos , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/citología , Multiómica , ARN Citoplasmático Pequeño/genética , ARN Citoplasmático Pequeño/metabolismo , RNA-Seq/métodos , Análisis de Secuencia de ARN/métodos , Análisis de Expresión Génica de una Sola Célula , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , TranscriptomaRESUMEN
The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system have hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only morphology and global gene expression profiles comparable to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into functional extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from preexisting primed PSCs and provide a valuable opportunity to study human placenta development and pathology from patients with placenta-related diseases.
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Placentación , Células Madre Pluripotentes , Trofoblastos , Biomarcadores , Proteína Morfogenética Ósea 4 , Diferenciación Celular , Femenino , Humanos , Modelos Biológicos , Placenta , Embarazo , Trofoblastos/metabolismoRESUMEN
Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).
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Astrocitos/metabolismo , Vesículas Extracelulares/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/metabolismo , Mitocondrias/metabolismo , Animales , Células Cultivadas , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Vesículas Extracelulares/genética , Vesículas Extracelulares/ultraestructura , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Inmunohistoquímica , Masculino , Potencial de la Membrana Mitocondrial/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Transmisión , Mitocondrias/genéticaRESUMEN
BACKGROUND & AIMS: Mesenchymal stem cells (MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs (UCMSCs) were differentiated into hepatocyte-like cells (hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadrupole time-of-flight mass spectrometry. Liver fibrosis was induced in mice by intraperitoneal injection of thioacetamide or CCl4; some mice were then given injections of secretomes or proteins. Liver tissues were collected and analyzed by histology or polymerase chain reaction array to analyze changes in gene expression patterns. We analyzed the effects of MSC secretomes and potential anti-fibrotic proteins on transforming growth factor ß 1 (TGFß1)-mediated activation of human hepatic stellate cell (HSC) lines (hTert-HSC and LX2) and human primary HSCs. Liver tissues were collected from 16 patients with liver cirrhosis and 16 individuals without cirrhosis (controls) in Korea and analyzed by immunohistochemistry and immunoblots. RESULTS: In mice with fibrosis, accumulation of extracellular matrix proteins was significantly reduced 3 days after injecting secretomes from UCMSCs, and to a greater extent from hpUCMSCs; numbers of activated HSCs that expressed the myogenic marker α-smooth muscle actin (α-SMA, encoded by ACTA2 [actin, alpha 2, smooth muscle]) were also reduced. Secretomes from UCMSCs, and to a greater extent from hpUCMSCs, reduced liver expression of multiple fibrotic factors, collagens, metalloproteinases, TGFß, and Smad proteins in the TGFß signaling pathways. In HSC cell lines and primary HSCs, TGFß1-stimulated upregulation of α-SMA was significantly inhibited (and SMAD2 phosphorylation reduced) by secretomes from UCMSCs, and to a greater extent from hpUCMSCs. We identified 32 proteins in secretomes of UCMSCs that were more highly concentrated in secretomes from hpUCMSCs and inhibited TGFß-mediated activation of HSCs. One of these, milk fat globule-EGF factor 8 (MFGE8), was a strong inhibitor of activation of human primary HSCs. We found MFGE8 to down-regulate expression of TGFß type I receptor by binding to αvß3 integrin on HSCs and to be secreted by MSCs from umbilical cord, teeth, and bone marrow. In mice, injection of recombinant human MFGE8 had anti-fibrotic effects comparable to those of the hpUCMSC secretome, reducing extracellular matrix deposition and HSC activation. Co-injection of an antibody against MFGE8 reduced the anti-fibrotic effects of the hpUCMSC secretome in mice. Levels of MFGE8 were reduced in cirrhotic liver tissue from patients compared with controls. CONCLUSIONS: MFGE8 is an anti-fibrotic protein in MSC secretomes that strongly inhibits TGFß signaling and reduces extracellular matrix deposition and liver fibrosis in mice.
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Antígenos de Superficie/metabolismo , Cirrosis Hepática/metabolismo , Proteínas de la Leche/metabolismo , Animales , Tetracloruro de Carbono/toxicidad , Línea Celular , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Células Estrelladas Hepáticas , Hepatocitos , Humanos , Integrina alfaVbeta3/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Masculino , Células Madre Mesenquimatosas/metabolismo , Metaboloma , Metaloproteasas/metabolismo , Ratones , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteína Smad2/metabolismo , Tioacetamida/toxicidad , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Plasmonic effects have been proposed as a solution to overcome the limited light absorption in thin-film photovoltaic devices, and various types of plasmonic solar cells have been developed. This review provides a comprehensive overview of the state-of-the-art progress on the design and fabrication of plasmonic solar cells and their enhancement mechanism. The working principle is first addressed in terms of the combined effects of plasmon decay, scattering, near-field enhancement, and plasmonic energy transfer, including direct hot electron transfer and resonant energy transfer. Then, we summarize recent developments for various types of plasmonic solar cells based on silicon, dye-sensitized, organic photovoltaic, and other types of solar cells, including quantum dot and perovskite variants. We also address several issues regarding the limitations of plasmonic nanostructures, including their electrical, chemical, and physical stability, charge recombination, narrowband absorption, and high cost. Next, we propose a few potentially useful approaches that can improve the performance of plasmonic cells, such as the inclusion of graphene plasmonics, plasmon-upconversion coupling, and coupling between fluorescence resonance energy transfer and plasmon resonance energy transfer. This review is concluded with remarks on future prospects for plasmonic solar cell use.
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Vascular compromise with impending skin necrosis is one of the most serious potential complications. Early recognition of vascular occlusion and swift and aggressive treatment are required to avoid any irreversible changes. However, initial symptoms of a vascular event are often dismissed as simple post-procedural discomfort. If more than 3 days pass after filler injection, crust formation is initiated over the erythematous base along with a rim of fibrous tissue. Due to the replacement of normal tissues by fibrous material, the healing process may result in scar formation in spite of debridement and aggressive dressing changes. Scars often cause contracture and subsequent cosmetic disfigurement, which results in a traumatic burden to the patient. By sharing our experience of the patients with filler induced skin necrosis, we suggest that treatment should be initiated no later than 3 days after the procedure.
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Materiales Biocompatibles/efectos adversos , Técnicas Cosméticas/efectos adversos , Rellenos Dérmicos/efectos adversos , Eritema/terapia , Primeros Auxilios/métodos , Piel/irrigación sanguínea , Tiempo de Tratamiento , Enfermedades Vasculares/terapia , Adulto , Materiales Biocompatibles/administración & dosificación , Rellenos Dérmicos/administración & dosificación , Eritema/diagnóstico , Eritema/etiología , Femenino , Humanos , Inyecciones Subcutáneas , Necrosis , Piel/patología , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiología , Cicatrización de HeridasRESUMEN
Multiple etiologies of liver injury are associated with fibrosis in which the key event is the activation of hepatic stellate cells (HSCs). Although microRNAs (miRNAs) are reportedly involved in fibrogenesis, the complete array of miRNA signatures associated with the disease has yet to be elucidated. Here, deep sequencing analysis revealed that compared to controls, 80 miRNAs were upregulated and 21 miRNAs were downregulated significantly in the thioacetamide (TAA)-induced mouse fibrotic liver. Interestingly, 58 of the upregulated miRNAs were localized to an oncogenic miRNA megacluster upregulated in liver cancer. Differential expression of some of the TAA-responsive miRNAs was confirmed, and their human orthologs were similarly deregulated in TGF-ß1-activated HSCs. Moreover, a functional analysis of the experimentally validated high-confidence miRNA targets revealed significant enrichment for the GO terms and KEGG pathways involved in HSC activation and liver fibrogenesis. This is the first comprehensive report of miRNAs profiles during TAA-induced mouse liver fibrosis.
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Regulación de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/genética , Hígado/metabolismo , MicroARNs/genética , Actinas/genética , Actinas/metabolismo , Animales , Línea Celular Transformada , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/patología , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Anotación de Secuencia Molecular , Transducción de Señal , Tioacetamida , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Filler granuloma is considered to be the result of delayed immune responses; growing evidence suggests that they may be secondary to biofilm formation. Dermal filler is technically a foreign body, and as the development of newer generations of dermal fillers lengthens their duration, it is possible that there is also an increased risk of biofilm formation. Here, we present a case report of a patient with Streptococcus sanguinis isolated from a filler granuloma, suggestive of biofilm formation. This case demonstrates the effective use of antibiotics after incision and drainage on antibiotic resistant biofilm.
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Antibacterianos/uso terapéutico , Biopelículas/efectos de los fármacos , Técnicas Cosméticas/efectos adversos , Rellenos Dérmicos/efectos adversos , Drenaje , Granuloma de Cuerpo Extraño/terapia , Infecciones Estreptocócicas/terapia , Streptococcus sanguis/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Biopsia , Terapia Combinada , Rellenos Dérmicos/administración & dosificación , Femenino , Granuloma de Cuerpo Extraño/diagnóstico , Granuloma de Cuerpo Extraño/microbiología , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/microbiología , Streptococcus sanguis/crecimiento & desarrollo , Streptococcus sanguis/aislamiento & purificación , Resultado del TratamientoRESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs) are promising therapeutic agents for various diseases. AIMS: To investigate the effects of conditioned medium from human bone marrow-derived mesenchymal stem cells (MSC-CdM) on pro-collagen production and wrinkle formation, we performed in vitro and in vivo experiments. METHODS: We assessed the effects of MSC-CdM on proliferation and photo-aging in human dermal fibroblasts after UVB exposure using enzyme activity assays for collagen type I secretion and MMP-1. To determine the effect of topically applied MSC-CdM on wrinkle formation, MSC-CdM (1% and 10%) and vehicle (propylene glycol: ethanol, 7 : 3) were applied to the dorsal skin of UVB-irradiated hairless mice for 8 weeks. We examined the effects on wrinkle formation by assessing visual skin grading, replica, tape stripping, transepidermal water loss (TEWL), and skin hydration measurement. We also examined histology of the lesions using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. RESULTS: MSC-CdM markedly reduced UV-induced matrix metalloproteinase-1 expression and increased pro-collagen synthesis in a dose-dependent manner. Our findings suggest that MSC-CdM induces repair of dermal damage and effacement of wrinkles on UVB-irradiated hairless mice through protective effect of hydration. CONCLUSION: These results support an anti-wrinkle effect of MSC-CdM that involves increased collagen synthesis and suggest that MSC-CdM might be a potential candidate for preventing UV-induced skin damage.
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Células Madre Mesenquimatosas , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Administración Cutánea , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Medios de Cultivo Condicionados/farmacología , Tejido Elástico/efectos de los fármacos , Tejido Elástico/patología , Tejido Elástico/efectos de la radiación , Femenino , Fibroblastos , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Ratones , Ratones Pelados , Procolágeno/biosíntesis , Piel/efectos de la radiación , Envejecimiento de la Piel/patología , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a common inflammatory skin disease that can affect all age groups. It has a relapsing course, which dramatically affects the quality of life of patients. A 308-nm excimer laser has been reported to be a safe and effective treatment for inflammatory skin diseases, although the range of potential application has not been fully explored. The purpose of this study was to evaluate the therapeutic effects of a 308-nm laser on AD-like skin lesions in NC/Nga mice. STUDY DESIGN/MATERIALS AND METHODS: Dermatophagoides farinae-exposed NC/Nga mice with a clinical score of 12 were treated with either a 308-nm excimer laser or narrowband-UVB (NB-UVB). The effects of the 308-nm excimer laser were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, including IgE and Th2-mediated cytokines. RESULTS: The 308-nm excimer laser significantly reduced the severity of skin lesions and decreased the total serum levels of IgE and Th2-mediated cytokines. The excimer laser also significantly reduced the inflammatory cellular infiltrate into AD-induced skin lesions. Moreover, treatment with the 308-nm excimer laser led to recovery of skin barrier function in AD-induced skin lesions. CONCLUSION: The 308-nm excimer laser can be considered a valid and safe therapeutic option for the treatment of localized AD. Lasers Surg. Med. 48:629-637, 2016. © 2016 Wiley Periodicals, Inc.
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Dermatitis Atópica/cirugía , Láseres de Excímeros/uso terapéutico , Animales , Biomarcadores/sangre , Citocinas/sangre , Dermatitis Atópica/sangre , Dermatitis Atópica/patología , Masculino , Ratones , Resultado del TratamientoRESUMEN
We investigated the potential of human dental pulp stem cells (hDPSCs) to differentiate into dopaminergic neurons in vitro as an autologous stem cell source for Parkinson's disease treatment. The hDPSCs were expanded in knockout-embryonic stem cell (KO-ES) medium containing leukemia inhibitory factor (LIF) on gelatin-coated plates for 3-4 days. Then, the medium was replaced with KO-ES medium without LIF to allow the formation of the neurosphere for 4 days. The neurosphere was transferred into ITS medium, containing ITS (human insulin-transferrin-sodium) and fibronectin, to select for Nestin-positive cells for 6-8 days. The cells were then cultured in N-2 medium containing basic fibroblast growth factor (FGF), FGF-8b, sonic hedgehog-N, and ascorbic acid on poly-l-ornithine/fibronectin-coated plates to expand the Nestin-positive cells for up to 2 weeks. Finally, the cells were transferred into N-2/ascorbic acid medium to allow for their differentiation into dopaminergic neurons for 10-15 days. The differentiation stages were confirmed by morphological, immunocytochemical, flow cytometric, real-time PCR, and ELISA analyses. The expressions of mesenchymal stem cell markers were observed at the early stages. The expressions of early neuronal markers were maintained throughout the differentiation stages. The mature neural markers showed increased expression from stage 3 onwards. The percentage of cells positive for tyrosine hydroxylase was 14.49%, and the amount was 0.526 ± 0.033 ng/mL at the last stage. hDPSCs can differentiate into dopaminergic neural cells under experimental cell differentiation conditions, showing potential as an autologous cell source for the treatment of Parkinson's disease.
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Diferenciación Celular , Pulpa Dental/citología , Neuronas Dopaminérgicas/citología , Neuronas Dopaminérgicas/metabolismo , Células Madre/citología , Células Madre/metabolismo , Animales , Encéfalo/patología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo/química , Medios de Cultivo/farmacología , Neuronas Dopaminérgicas/patología , Ensayo de Inmunoadsorción Enzimática , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Ratones , Ratones Endogámicos ICR , Proteína Básica de Mielina/genética , Proteína Básica de Mielina/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Antígenos Embrionarios Específico de Estadio/genética , Antígenos Embrionarios Específico de Estadio/metabolismo , Células Madre/patología , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Tirosina 3-Monooxigenasa/análisis , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Phototherapy with 311-nm narrowband-UVB (NBUVB) is an effective adjuvant treatment modality for atopic dermatitis (AD). In this study, we evaluated the therapeutic effect of the newly developed gain-switched 311-nm Ti:Sapphire laser device using a NC/Nga mouse AD model. A total number of 50 mice were used in this study. Atopic dermatitis (AD) was induced in mice by exposure to Dermatophagoides farina. These, NC/Nga mice were then treated with conventional 311-nm NBUVB or the newly developed gain-switched 311-nm Ti:Sapphire laser. The clinical features, dermatitis severity scores, and scratching behavior were assessed. In addition, serologic analyses including inflammatory cytokines and histological analyses were performed. Gain-switched 311-nm Ti:Sapphire laser improved the AD-like skin lesions, severity, and symptoms of AD in the NC/Nga mouse model. This new laser also modulated the immune response found in the AD model, including hyper-IgE, upregulated Th2 cytokines, and the Th2-mediated allergic inflammatory reaction. Gain-switched 311-nm Ti:Sapphire laser shows therapeutic promise via an immune-modulation mechanism in an AD mouse model. These data suggest that gain-switched 311-nm Ti:Sapphire laser may be useful as a targeted phototherapy modality for AD.
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Óxido de Aluminio/química , Dermatitis Atópica/radioterapia , Terapia por Láser , Animales , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Inmunoglobulina E/biosíntesis , Inflamación/inmunología , Inflamación/patología , Mediadores de Inflamación/metabolismo , Ratones , Piel/patología , Piel/efectos de la radiación , Células Th2/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: Ultraviolet light-emitting diodes (UV-LEDs) are a novel light source for phototherapy. This research investigated the in vitro safety and efficacy of UV-LEDs as a phototherapeutic device for atopic dermatitis (AD). STUDY DESIGN/MATERIALS AND METHODS: Human keratinocytes and fibroblasts were irradiated by UV-LEDs with a center wavelength of 310 and 340 nm. We examined the effects of UV-LED irradiation on the suppression of TNF-α/IFN-γ-induced activation of STAT1 and ICAM-1 and on NF-κB expression; we used the following methods: cell viability assay, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and immunocytochemistry. RESULTS: We observed anti-inflammatory responses through the suppression of TNF-α/IFN-γ-induced expression of TARC and MCP-1/CCL2, IL-1beta, IL-6, and sICAM-1 via blockage of ICAM-1 activation and subsequent activation of STAT1 and NF-κB. The results suggested that UV-LED irradiation inhibited ICAM expression by suppressing TNF-α/IFN-γ-induced NF-κB activation in vitro. CONCLUSION: We concluded that novel UV-LED (310 and 340 nm) modalities were effective for the treatment of AD and may be promising for the treatment of inflammatory skin diseases.
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Molécula 1 de Adhesión Intercelular/metabolismo , Interferón gamma/metabolismo , Queratinocitos/efectos de la radiación , Fosforilación/efectos de la radiación , Factor de Transcripción STAT1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Rayos Ultravioleta , Biomarcadores/metabolismo , Western Blotting , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Humanos , Inmunohistoquímica , Queratinocitos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Terapia Ultravioleta/instrumentaciónRESUMEN
We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold(heparin-bFGF) group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 µL/cm H2O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 µL/cm H2O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 µL/cm H2O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 µL/cm H2O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 µL/cm H2O for the scaffold(heparin-bFGF) group, respectively). In histological and immunohistochemical analysis, the USC-scaffold(heparin-bFGF) group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold(heparin-bFGF) exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.
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Células Madre Adultas/trasplante , Ingeniería de Tejidos/métodos , Vejiga Urinaria/cirugía , Orina/citología , Células Madre Adultas/citología , Células Madre Adultas/metabolismo , Animales , Materiales Biocompatibles/química , Diferenciación Celular , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Heparina/administración & dosificación , Humanos , Ensayo de Materiales , Modelos Animales , Poloxámero , Poliésteres , Ratas , Procedimientos de Cirugía Plástica , Regeneración , Andamios del Tejido/química , Vejiga Urinaria/anatomía & histología , Vejiga Urinaria/fisiologíaRESUMEN
In this study, sulfur-doped graphene (S-graphene) was synthesized by thermal treatment of exfoliated graphene under CS2 gas flow. Its electrocatalytic activity as a metal-free catalyst was evaluated and compared with other doped-graphenes and commercial platinum nanoparticles loaded on carbon black (Pt/C) catalysts for oxygen reduction reaction (ORR) in fuel cell cathodes. The resultant S-graphene was shown to act as a viable catalyst for ORR and its limiting current density and durability were improved compared to those of the commercial Pt/C catalyst. The current density at -1.0 V for the commercial Pt/C catalyst, pristine graphene, nitrogen-doped graphene (N-graphene) and S-graphene was 4.7, 0.15, 6.26 and 6.99 mA cm(-2), respectively. The durability of S-graphene (70.3%) was much better compared to commercial Pt/C (37.2%) and N-graphene (67.9%). When S-graphene was used as a supporting material for Pt nanoparticles, its catalytic performance was significantly higher than other Pt catalysts supported on different doped graphenes. Here, we demonstrate that S-graphene can be used as a novel graphene-based efficient metal-free ORR catalyst in fuel cells.
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Hierarchically organized mesoporous carbon-TiO2 inverse opal nanostructures were synthesized by complementary colloid and block copolymer (BCP) self-assembly, where the triblock copolymer P123 acts simultaneously as the template and the carbon source. Highly ordered mesoporous inverse opal nanostructures with a nano-textured surface morphology and multiple-length scale nanopores provide increased light-activated surface area and scattering effects, leading to enhanced photoabsorption efficiency and the transport of matter. UV-vis absorption, X-ray photoelectron spectroscopy and Mott-Schottky measurement studies show that incorporation of carbon moieties into TiO2via direct conversion of BCPs creates a new energy level above the valence band of TiO2, resulting in an effective decrease in the band gap. A significantly enhanced visible light photocatalytic activity was demonstrated for the mesoporous carbon-TiO2 inverse opals in terms of the degradation of p-nitrophenol (~79%) and photoelectrochemical water splitting (~0.087%).
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BACKGROUND: Although various reconstructive flap surgeries have been successfully performed, there still are difficult wound complications, such as seroma formation, wound margin necrosis, delayed wound healing, and even flap failures. The negative-pressure wound therapy has been described in detail in the literature to assist open chronic/complex wound closure in reconstructive surgery. However, the negative-pressure wound therapy was difficult to be applied under the incisional closed wounds. METHODS: A total of 23 patients underwent the various reconstructive flap surgeries with continuous high-pressure negative suction drain. Instead of using regular suction units, Barovac (50-90 mm Hg, Sewoon Medical, Seoul, Republic of Korea) drainage tubes were connected to the wall suction unit, providing continuous high-powered negative pressure. In addition, continuous subatmospheric suction pressure (100-300 mm Hg) was applied. Outcome of the measures was obtained from the incidence of seroma, volume of postoperative drainage, hospitalization period, and incidence of other typical wound complications. Dead space was evaluated postoperatively with ultrasonography. RESULTS: Using continuous high-pressure negative suction drain, successful management of seroma was obtained without any major complication such as wound infection, flap loss, and wound margin necrosis, except for only 1 case of seroma after discharge from the hospital. The indwelling time of the drain in the latissimus dorsi donor site was significantly reduced in comparison with the authors' previous data (P = 0.047). The volume of drainage and hospitalization period were also reduced; however, these were not statistically significant. The dead space with continuous high-pressure negative suction drain was more reduced than in the control group in the immediate postoperative period and confirmed with ultrasonography. CONCLUSIONS: Continuous high-pressure negative suction drain might be the simple and powerful solution in the management of challenging closed wounds.
Asunto(s)
Terapia de Presión Negativa para Heridas/instrumentación , Terapia de Presión Negativa para Heridas/métodos , Complicaciones Posoperatorias/terapia , Seroma/terapia , Succión/instrumentación , Succión/métodos , Colgajos Quirúrgicos/cirugía , Adolescente , Adulto , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
During human pregnancy, extravillous trophoblasts play crucial roles in placental invasion into the maternal decidua and spiral artery remodeling. However, regulatory factors and their action mechanisms modulating human extravillous trophoblast specification have been unknown. By analyzing dynamic changes in transcriptome and enhancer profile during human trophoblast stem cell to extravillous trophoblast differentiation, we define stage-specific regulators, including an early-stage transcription factor, TFAP2C, and multiple late-stage transcription factors. Loss-of-function studies confirm the requirement of all transcription factors identified for adequate differentiation, and we reveal that the dynamic changes in the levels of TFAP2C are essential. Notably, TFAP2C pre-occupies the regulatory elements of the inactive extravillous trophoblast-active genes during the early stage of differentiation, and the late-stage transcription factors directly activate extravillous trophoblast-active genes, including themselves as differentiation further progresses, suggesting sequential actions of transcription factors assuring differentiation. Our results reveal stage-specific transcription factors and their inter-connected regulatory mechanisms modulating extravillous trophoblast differentiation, providing a framework for understanding early human placentation and placenta-related complications.
Asunto(s)
Trofoblastos Extravellosos , Placenta , Embarazo , Humanos , Femenino , Trofoblastos , Diferenciación Celular/genética , Factores de Transcripción/genética , Células MadreRESUMEN
Hybrid Pt(platinum)/carbon nanopatterns with an extremely low loading level of Pt catalysts derived from block copolymer templates as an alternative type of counter electrodes (CEs) in dye-sensitized solar cells (DSSCs) are proposed. DSSCs employing hybrid Pt/carbon with tailored configuration as CEs exhibit higher short-circuit current and conversion efficiencies as well as stability with a lapse of time compared with conventional cells on the basis of sputtered Pt thin films, evidencing that the new class of hybrid nanostructures possess high potential for cost-effective electrodes in energy conversion devices.
Asunto(s)
Carbono/química , Nanopartículas/química , Platino (Metal)/química , Energía Solar , Catálisis , Colorantes , Electrodos , Polímeros/químicaRESUMEN
Dermatofibroma is a firm, skin-colored or reddish-brown sessile papule or nodule. It arises spontaneously without a known cause or after a minor trauma, such as an insect bite. A 39-year-old Asian woman complained of a palpable mass and tenderness in the right upper eyelid. On physical examination, a firm palpable subcutaneous mass was detected in the upper eyelid. Surgical exploration under local anesthesia showed a fibrotic and firmly attached mass to the tarsal plate. In histopathologic examination, the mass was characterized by a fibroblast proliferation in the dermis with an overlying hyperplastic epidermis with frequent basal hyperpigmentation. As far as we know, there have been no previous reports of dermatofibroma located on the tarsal plate. This article is a good example for intratarsal location of dermatofibroma.