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1.
Neuron ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34644545

RESUMO

Impairment in glucocerebrosidase (GCase) is strongly associated with the development of Parkinson's disease (PD), yet the regulators responsible for its impairment remain elusive. In this paper, we identify the E3 ligase Thyroid Hormone Receptor Interacting Protein 12 (TRIP12) as a key regulator of GCase. TRIP12 interacts with and ubiquitinates GCase at lysine 293 to control its degradation via ubiquitin proteasomal degradation. Ubiquitinated GCase by TRIP12 leads to its functional impairment through premature degradation and subsequent accumulation of α-synuclein. TRIP12 overexpression causes mitochondrial dysfunction, which is ameliorated by GCase overexpression. Further, conditional TRIP12 knockout in vitro and knockdown in vivo promotes the expression of GCase, which blocks α-synuclein preformed fibrils (α-syn PFFs)-provoked dopaminergic neurodegeneration. Moreover, TRIP12 accumulates in human PD brain and α-synuclein-based mouse models. The identification of TRIP12 as a regulator of GCase provides a new perspective on the molecular mechanisms underlying dysfunctional GCase-driven neurodegeneration in PD.

2.
Nat Commun ; 12(1): 5008, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429436

RESUMO

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.


Assuntos
Técnicas Biossensoriais/métodos , Fontes de Energia Elétrica , Pressão , Temperatura , Tecnologia sem Fio , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Pele , Termografia/instrumentação , Termografia/métodos
3.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209900

RESUMO

Adult human cardiomyocytes have an extremely limited proliferative capacity, which poses a great barrier to regenerative medicine and research. Human embryonic stem cells (hESCs) have been proposed as an alternative source to generate large numbers of clinical grade cardiomyocytes (CMs) that can have potential therapeutic applications to treat cardiac diseases. Previous studies have shown that bioactive lipids are involved in diverse cellular responses including cardiogenesis. In this study, we explored the novel function of the chemically synthesized bioactive lipid O-cyclic phytosphingosine-1-phosphate (cP1P) as an inducer of cardiac differentiation. Here, we identified cP1P as a novel factor that significantly enhances the differentiation potential of hESCs into cardiomyocytes. Treatment with cP1P augments the beating colony number and contracting area of CMs. Furthermore, we elucidated the molecular mechanism of cP1P regulating SMAD1/5/8 signaling via the ALK3/BMP receptor cascade during cardiac differentiation. Our result provides a new insight for cP1P usage to improve the quality of CM differentiation for regenerative therapies.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Esfingosina/análogos & derivados , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/fisiologia , Humanos , Lipídeos/química , Lipídeos/farmacologia , Miócitos Cardíacos/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Esfingosina/química , Esfingosina/farmacologia
4.
J Tissue Eng Regen Med ; 15(10): 807-817, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34310055

RESUMO

Here, we present a novel in vitro maturation (IVM) system comprising an agarose matrix supplemented with extracellular matrix (ECM) proteins for enhanced maturation of immature oocytes within cumulus-oocyte complexes (COCs) derived from porcine medium antral follicles (MAFs). Immunocytochemical analyses of integrin subunit α2 , α5 , α6 , ß1 , and ß4 expression suggested that integrin α2 ß1 , α5 ß1 , α6 ß1 , and α6 ß4 play pivotal roles in IVM of porcine immature oocytes. Combinatorial supplementation of fibronectin interacting with integrin α5 ß1 , collagen interacting with integrin α2 ß1 , and laminin interacting with integrin α6 ß1 and α6 ß4 to the agarose matrix had no significant effect on nuclear maturation. However, the number of parthenogenetic embryos that developed into blastocysts increased when oocytes were matured using agarose IVM matrices supplemented with fibronectin, collagen, or laminin. Furthermore, significant increases in cytoplasmic maturation-related parameters (BMP15 level, cumulus cell expansion score, intra-oocyte ATP level, and index of cortical granule distribution) were observed in COCs matured in vitro using ECM protein-incorporated agarose matrices. Our data suggest that mature porcine oocytes with enhanced developmental competence and high-quality cytoplasm can be generated via IVM using agarose matrices supplemented with fibronectin, collagen, or laminin.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34180652

RESUMO

In this study, the oxygen scavenger layer (OSL) is proposed as a back channel in the bilayer channel to enhance both the electrical characteristics and stability of an amorphous indium-gallium-zinc oxide thin-film transistor (a-IGZO TFT) and also to enable its fabrication at low temperature. The OSL is a hafnium (Hf)-doped a-IGZO channel layer deposited by radio-frequency magnetron cosputtering. Amorphous IGZO TFTs with the OSL, even if annealed at a low temperature (200 °C), exhibited improved electrical characteristics and stability under positive bias temperature stress (PBTS) compared to those without the OSL, specifically in terms of field-effect mobility (31.08 vs 9.25 cm2/V s), on/off current ratio (1.73 × 1010 vs 8.68 × 108), and subthreshold swing (0.32 vs 0.43 V/decade). The threshold voltage shift under PBTS at 50 °C for 10,000 s decreased from 9.22 to 2.31 V. These enhancements are attributed to Hf in the OSL, which absorbs oxygen ions from the a-IGZO front channel near the interface between a-IGZO and the OSL.

6.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070420

RESUMO

Oct4 is an important mammalian POU family transcription factor expressed by early human embryonic stem cells (hESCs). The precise level of Oct4 governs the pluripotency and fate determination of hESCs. Several post-translational modifications (PTMs) of Oct4 including phosphorylation, ubiquitination, and SUMOylation have been reported to regulate its critical functions in hESCs. Ubiquitination and deubiquitination of Oct4 should be well balanced to maintain the pluripotency of hESCs. The protein turnover of Oct4 is regulated by several E3 ligases through ubiquitin-mediated degradation. However, reversal of ubiquitination by deubiquitinating enzymes (DUBs) has not been reported for Oct4. In this study, we generated a ubiquitin-specific protease 3 (USP3) gene knockout using the CRISPR/Cas9 system and demonstrated that USP3 acts as a protein stabilizer of Oct4 by deubiquitinating Oct4. USP3 interacts with endogenous Oct4 and co-localizes in the nucleus of hESCs. The depletion of USP3 leads to a decrease in Oct4 protein level and loss of pluripotent morphology in hESCs. Thus, our results show that USP3 plays an important role in controlling optimum protein level of Oct4 to retain pluripotency of hESCs.


Assuntos
Carcinoma Embrionário/genética , Enzimas Desubiquitinantes/metabolismo , Células-Tronco Embrionárias/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Sistemas CRISPR-Cas , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Enzimas Desubiquitinantes/genética , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/enzimologia , Técnicas de Inativação de Genes , Humanos , Fator 3 de Transcrição de Octâmero/genética , Ligação Proteica , Processamento de Proteína Pós-Traducional , Estabilidade Proteica , Análise de Célula Única , Proteases Específicas de Ubiquitina/genética , Ubiquitinação/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-33448781

RESUMO

We investigated a facile fabrication method, which is an insertion of a carrier-induced interlayer (CII) between the oxygen-rich a-IGZO channel and the gate insulator to improve the electrical characteristics and stability of amorphous indium-gallium-zinc-oxide thin-film transistors (a-IGZO TFTs). The a-IGZO channel is deposited with additional oxygen gas flow during a-IGZO channel deposition to improve the stability of the a-IGZO TFTs. The CII is a less than 10 nm thick deposited thin film that acts to absorb the oxygen from the a-IGZO front channel through oxidation. Through oxidation of the CII, the oxygen concentration of the a-IGZO front channel is decreased compared to that of the oxygen-rich back channel, which forms a vertically graded oxygen deficiency (VGO) in the a-IGZO channel. Therefore, the electrical characteristics of the VGO TFTs are improved by increasing the carrier concentration of the front channel as the oxygen vacancy concentration in the front channel is increased through the oxidation of the CII. At the same time, the stability of the VGO TFTs is improved by maintaining a high oxygen concentration in the back channel even after oxidation of the CII. The field-effect mobility (µFET) of the VGO TFTs improved compared to that of the a-IGZO TFTs from 7.16 ± 0.6 to 12.0 ± 0.7 cm2/V·s. The threshold voltage (Vth) shifts under positive bias temperature stress and negative bias temperature illumination stress decreased from 6.00 to 2.95 V and -15.58 to -8.99 V, respectively.

9.
Langmuir ; 36(30): 8939-8946, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32610911

RESUMO

Soft strain sensors have attracted significant attention in wearable human motion monitoring applications. However, there is still a huge challenge for decoupled measurement of multidirectional strains. In this study, we have developed a biaxial and stretchable strain sensor based on a carbon nanotube (CNT) film and a microdome array (MA)-patterned elastomeric substrate. The MA structures lead to generating localized and directional microcracks of CNT films within the intended regions under tensile strain. This mechanism allows a single sensing layer to act as a strain sensor capable of decoupling the biaxial strains into axial and transverse terms. The ratio of resistance change between two perpendicular axes is about 960% under an x-directional strain of 30%, demonstrating the biaxial decoupling capability. Also, the proposed strain sensor shows high stretchability and excellent long-term reliability under a cyclic loading test. Finally, wearable devices integrated with the strain sensor have been successfully utilized to monitor various human motions of the wrist, elbow, knee, and fingers by measuring joint bending and skin elongation.


Assuntos
Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Humanos , Movimento (Física) , Reprodutibilidade dos Testes
10.
BMC Gastroenterol ; 20(1): 193, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552662

RESUMO

BACKGROUND: Recently, a new international bleeding score was developed to predict 30-day hospital mortality in patients with upper gastrointestinal bleeding (UGIB). However, the efficacy of this newly developed scoring system has not been extensively investigated. We aimed to validate a new scoring system for predicting 30-day mortality in patients with non-variceal UGIB and determine whether a higher score is associated with re-bleeding, length of hospital stay, and endoscopic failure. METHODS: A retrospective study was performed on 905 patients with acute non-variceal UGIB who were examined in our hospital between January 2013 and December 2017. Baseline characteristics, endoscopic findings, re-bleeding, admission, and mortality were reviewed. The 30-day mortality rate of the new international bleeding risk score was calculated using the receiver operating characteristic curves and compared to the pre-endoscopy Rockall score, AIMS65, Glasgow Blatchford score, and Progetto Nazionale Emorragia Digestiva score. To verify the variable for the 30-day mortality of the new scoring system, we performed multivariate logistic regression using our data and further analyzed the score items. RESULTS: The new international bleeding scoring system showed higher receiver operating characteristic (ROC) curve values in predicting mortality (area under ROC curve 0.958; [95% confidence interval (CI)]), compared with such as AIMS65 (AUROC, 0.832; 95%CI, 0.806-0.856; P < 0.001), PNED (AUROC, 0.865; 95%CI, 0.841-0.886; P < 0.001), Pre-RS (AUROC, 0.802; 95%CI, 0.774-0.827; P < 0.001), and GBS (AUROC, 0.765; 95%CI, 0.736-0.793; P < 0.001). Multivariate analysis was performed using our data and showed that the 30-day mortality rate was related to multiple comorbidities, blood urea nitrogen, creatinine, albumin, syncope at first visit, and endoscopic failure within 24 h during the first admission. In addition, in the high-score group, relatively long hospital stay, re-bleeding, and endoscopic failure were observed. CONCLUSION: This is a preliminary report of a new bleeding score which may predict 30-day mortality better than the other scoring systems. High-risk patients could be screened using this new scoring system to predict 30-day mortality. The use of this scoring system seemed to improve the outcomes of non-variceal UGIB patients in this study, through proper management and intervention.


Assuntos
Hemorragia Gastrointestinal/mortalidade , Medição de Risco/normas , Índice de Gravidade de Doença , Trato Gastrointestinal Superior/irrigação sanguínea , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco
11.
Cell Death Differ ; 27(12): 3273-3288, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32555450

RESUMO

Brpf-histone acetyltransferase (HAT) complexes have important roles in embryonic development and regulating differentiation in ESCs. Among Brpf family, Brpf3 is a scaffold protein of Myst2 histone acetyltransferase complex that plays crucial roles in gene regulation, DNA replication, development as well as maintaining pluripotency in embryonic stem cells (ESCs). However, its biological functions in ESCs are not elucidated. In this study, we find out that Brpf3 protein level is critical for Myst2 stability and E3 ligase Huwe1 functions as a novel negative regulator of Myst2 via ubiquitin-mediated degradation. Importantly, Brpf3 plays an antagonistic role in Huwe1-mediated degradation of Myst2, suggesting that protein-protein interaction between Brpf3 and Myst2 is required for retaining Myst2 stability. Further, Brpf3 overexpression causes the aberrant upregulation of Myst2 protein levels which in turn induces the dysregulated cell-cycle progression and also delay of early embryonic development processes such as embryoid-body formation and lineage commitment of mouse ESCs. The Brpf3 overexpression-induced phenotypes can be reverted by Huwe1 overexpression. Together, these results may provide novel insights into understanding the functions of Brpf3 in proper differentiation as well as cell-cycle progression of ESCs via regulation of Myst2 stability by obstructing Huwe1-mediated ubiquitination. In addition, we suggest that this is a useful report which sheds light on the function of an unknown gene in ESC field.

12.
In Vitro Cell Dev Biol Anim ; 56(6): 435-443, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32572848

RESUMO

In vivo, melanocytes occupy three-dimensional (3D) space. Nevertheless, most experiments involving melanocytes are performed in a two-dimensional microenvironment, resulting in difficulty obtaining accurate results. Therefore, it is necessary to construct an artificial in vivo-like 3D microenvironment. Here, as a step towards engineering a precisely defined acellular 3D microenvironment supporting the maintenance of human epidermal melanocytes (HEMs), we examined the types of integrin heterodimers that are expressed transcriptionally, translationally, and functionally in HEMs. Real-time PCR and fluorescent immunoassay analyses were used to elucidate the expression of integrin α and ß subunit genes at the transcriptional and translational levels, respectively. The functionality of the presumed integrin heterodimers was confirmed using attachment and antibody-inhibition assays. Among the genes encoding 12 integrin subunits (α1, α2, α3, α4, α5, α6, α7, αV, ß1, ß3, ß5, and ß8) showing significantly higher transcription levels, proteins translated from the integrin α2, α4, α5, ß1, ß3, and ß5 subunit genes were detected on the surface of HEMs. These HEMs showed significantly increased adhesion to collagen I, fibronectin, laminin, and vitronectin, and functional blockade of the integrin α2 subunits significantly inhibited adhesion to collagen I, fibronectin, and laminin. In addition, there was no significant inhibition of the adhesion to fibronectin or vitronectin in HEMs with functional blockade of the integrin α4, α5, or αV subunits. These results indicate that the active integrin α2ß1 heterodimer and the inactive integrin α4, α5, αV, ß3, and ß5 subunits are all localized on the surface of HEMs.

13.
Tissue Cell ; 63: 101323, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223958

RESUMO

Previous reports showed that fibronectin (FN) was effective in stimulating the recovery of damaged dermis. However, native FN has multifunctional domains transmitting beneficial as well as unbeneficial signals to dermal tissue cells through the mediation of integrin heterodimers. The use of a functional domain [FN type III9-10 fragments (FNIII9-10)] providing beneficial effects on the physiology of dermal tissue cells would enhance an in vitro culture system for dermal fibroblasts (DFs). We therefore investigated the FNIII9-10-derived extracellular signaling effect on the physiology of DFs during in vitro culture. Recombinant FNIII9-10 proteins were constructed and their functionality was determined by observing the adhesion of adult human DFs (aHDFs) to recombinant FNIII9-10 and of low adhesion integrin α5ß1- and αvß3-blocked aHDFs to recombinant FNIII9-10. Cellular proliferation, morphology, and senescence were measured and compared in the aHDFs cultured on native FN and recombinant FNIII9-10 for short or long periods. The results show that recombinant FNIII9-10-derived extracellular signaling stimulated increased proliferation of aHDF (both in short- and long-term cultures) and inhibited the generation of morphological abnormalities (in short- and long-term cultures) and cellular senescence (long-term culture) when compared with native FN-derived extracellular signaling. Our results suggest that, instead of native FN, recombinant FNIII9-10 better enhanced the in vitro culture of aHDFs while diminishing the adverse effects associated with the use of human-derived materials.


Assuntos
Senescência Celular/genética , Derme/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibronectinas/genética , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Proliferação de Células/genética , Células Cultivadas , Derme/metabolismo , Fibroblastos/metabolismo , Domínio de Fibronectina Tipo III/genética , Fibronectinas/farmacologia , Humanos , Integrina alfa5beta1/genética , Transdução de Sinais/genética
14.
PLoS One ; 14(10): e0224614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31671169

RESUMO

Additional surgical resection should be considered for the patients with pathological findings beyond the expanded criteria with the risk for LN metastasis. However, close observation without additional surgery may be applied because of various reasons. We aimed to determine the clinical outcomes of early gastric cancer beyond the expanded criteria after endoscopic resection according to the pathological extent. A total of 288 patients with 289 lesions beyond the expanded criteria of endoscopic submucosal dissection for early gastric cancer were analyzed between 2005 and 2016, and classified into two groups according to additional treatment: observation (n = 175 patients, 175 lesions) and surgery (n = 113 patients, 114 lesions). The depth of tumor invasion was greater and the tumor-positive vertical margin and lymphatic and venous invasion were more common in the surgery group than in the observation group (P<0.001). Residual, synchronous, and metachronous tumors were more common in the observation group; however, the occurrence of regional lymph node and distant metastasis did not differ between the groups. Overall survival and 5-year disease-specific survival did not differ between the groups (observation vs surgery, 88.6 vs 93.8%; P = 0.259, 98.2 vs 100%; P = 0.484, respectively), but the 5-year disease-free survival was lower in the observation group (73.5 vs 97.9%; P<0.001). On multivariate analysis, tumor-positive lateral margin was a risk factor for residual tumor and lymphatic and venous invasion were risk factors for regional lymph node metastasis. In conclusion, the clinical course of beyond the expanded criteria of endoscopic submucosal dissection for early gastric cancer showed good prognosis over 98% in 5-year disease specific survival. If additional surgery cannot be performed, a close follow-up with endoscopy and abdominal computed tomography can be considered as an alternative for carefully selected patients without lymphatic and vascular invasion.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Idoso , Intervalo Livre de Doença , Detecção Precoce de Câncer/métodos , Endoscopia , Feminino , Gastrectomia/métodos , Mucosa Gástrica/patologia , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgia
15.
BMC Gastroenterol ; 19(1): 136, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349816

RESUMO

BACKGROUND: Risk stratification for patients with nonvariceal upper gastrointestinal (NVUGI) bleeding is crucial for successful prognosis and treatment. Recently, the AIMS65 score has been used to predict mortality risk and rebleeding. The purpose of this study was to compare the performance of the AIMS65 score with the Glasgow-Blatchford score (GBS), Rockall score, and pre-endoscopic Rockall score in Korea. METHODS: We retrospectively studied 512 patients with NVUGI bleeding who were treated at a university hospital between 2013 and 2016. The AIMS65, GBS, Rockall score, and pre-endoscopic Rockall score were used to stratify patients based on their bleeding risk. The primary outcome was in-hospital mortality. The secondary outcomes were composite clinical outcomes of mortality, rebleeding, and intensive care unit (ICU) admission. Each scoring system was compared using the receiver-operating curve (ROC). RESULTS: A total of 17 patients (3.3%) died and rebleeding developed in 65 patients (12.7%). Eighty-six patients (16.8%) required ICU admission. The AIMS65 (area under the curve (AUC) 0.84, 95% confidence interval, 0.81-0.88)) seemed to be superior to the GBS (AUC 0.72, 0.68-0.76), the Rockall score (AUC 0.75, 0.71-0.79), or the pre-endoscopic Rockall score (AUC 0.74, 0.70-0.78) in predicting in-hospital mortality, but there was not a statistically significant difference between the groups (P = 0.07). The AUC value of the AIMS65 was not significantly different from the other scoring systems in prediction of rebleeding, endoscopic intervention, or ICU admission. CONCLUSIONS: The AIMS65 score in NVUGI bleeding patients was comparable to the GBS or Rockall scoring systems when predicting the mortality, rebleeding, or ICU admission. Because AIMS65 is a much easier, readily calculated scoring system compared to the others, we would recommend using the AIMS65 in daily practice.


Assuntos
Hemorragia Gastrointestinal/mortalidade , Trato Gastrointestinal Superior , Idoso , Idoso de 80 Anos ou mais , Varizes Esofágicas e Gástricas , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
16.
ACS Appl Mater Interfaces ; 11(26): 23639-23648, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31180635

RESUMO

Flexible and wearable pressure sensors have attracted a tremendous amount of attention due to their wider applications in human interfaces and healthcare monitoring. However, achieving accurate pressure detection and stability against external stimuli (in particular, bending deformation) over a wide range of pressures from tactile to body weight levels is a great challenge. Here, we introduce an ultrawide-range, bending-insensitive, and flexible pressure sensor based on a carbon nanotube (CNT) network-coated thin porous elastomer sponge for use in human interface devices. The integration of the CNT networks into three-dimensional microporous elastomers provides high deformability and a large change in contact between the conductive CNT networks due to the presence of micropores, thereby improving the sensitivity compared with that obtained using CNT-embedded solid elastomers. As electrical pathways are continuously generated up to high compressive strain (∼80%), the pressure sensor shows an ultrawide pressure sensing range (10 Pa to 1.2 MPa) while maintaining favorable sensitivity (0.01-0.02 kPa-1) and linearity ( R2 ∼ 0.98). Also, the pressure sensor exhibits excellent electromechanical stability and insensitivity to bending-induced deformations. Finally, we demonstrate that the pressure sensor can be applied in a flexible piano pad as an entertainment human interface device and a flexible foot insole as a wearable healthcare and gait monitoring device.


Assuntos
Técnicas Biossensoriais , Elastômeros/química , Nanotubos de Carbono/química , Dispositivos Eletrônicos Vestíveis , Elastômeros/uso terapêutico , Condutividade Elétrica , Humanos , Porosidade , Pressão
17.
In Vitro Cell Dev Biol Anim ; 55(3): 177-188, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30725355

RESUMO

Spermatogonial stem cells (SSCs) are a useful tool for the generation of genetically modified transgenic sperm. As a result, the transfer of specific genes into the cytoplasm of SSCs is crucial for the successful generation of transgenic sperm. Here, we report electroporation conditions optimized for SSCs derived from the porcine testis. The highest transfection efficiency and cell viability were observed in porcine SSCs transfected with 1 µg transgenic vector with a single electric pulse from an electroporator at a voltage of 100 V and a capacitor setting of 250 µF. The transfection efficiency and cell viability were constant regardless of the size of the transgenic vector. Furthermore, we did not detect loss of spermatozoa differentiation potential in the transfected porcine SSCs. From these results, we confirm that this electroporation-based gene delivery system can effectively introduce foreign DNA into the genome of porcine SSCs without any loss of the original porcine SSC characteristics, which will be important in the generation of mosaicism-free transgenic pigs produced from transgenic porcine sperm.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , Eletroporação/métodos , Técnicas de Transferência de Genes , Células-Tronco Germinativas Adultas/citologia , Células-Tronco Germinativas Adultas/transplante , Animais , Animais Geneticamente Modificados , Blastocisto/fisiologia , Diferenciação Celular , Sobrevivência Celular , Fertilização In Vitro , Vetores Genéticos , Masculino , Espermatozoides/citologia , Espermatozoides/fisiologia , Suínos , Transfecção/métodos
18.
Biomaterials ; 193: 22-29, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30553129

RESUMO

Transgenic pigs are quite useful in many biomedical fields, such as xenotransplantation research and the production of biopharmaceutical materials. The genetic transformation of porcine spermatogonial stem cells (pSSCs) followed by differentiation into mature spermatozoa enables the effective production of transgenic pigs. Improving the transfection efficiency of pSSCs, however, has been much desired. Herein, we report the efficient genetic modification of pSSCs by using an electrically responsive Au nanowire injector (E-R Au NWI). This is the first study that shows an exogenous gene is directly delivered into the nucleus of a pSSC by using a 1-dimensional nanomaterial and then successfully expressed to produce a protein. The E-R Au NWI interfaced noninvasively with the nucleus of the pSSC, and the pEGFP-N1 plasmid was delivered by the application of an electrical stimulus without cell damage. Compared to the results of conventional nonviral vector-based gene delivery methods such as jetPEI, Lipofectamine, and electroporation, the E-R Au NWI-based method improved the pSSC transfection efficiency by at least 6.7-fold and even up to 46.7-fold. Furthermore, we successfully obtained transgenic pSSCs containing the human bone morphogenetic protein 2 gene by using E-R Au NWIs. This result suggests that the E-R Au NWI enables the efficient genetic modification of pSSCs and can be employed to produce diverse kinds of transgenic pigs.


Assuntos
Ouro/química , Nanofios/química , Espermatogônias/metabolismo , Animais , Animais Geneticamente Modificados , Eletroporação , Técnicas de Transferência de Genes , Humanos , Masculino , Suínos
19.
Gut Liver ; 12(5): 523-529, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29938460

RESUMO

Background/Aims: Although forceps biopsy is performed for suspicious gastric tumors during endoscopy, it is difficult to determine treatment strategies for atypical gastric glands due to uncertainty of the diagnosis. The aim of this study was to investigate clinical implications and risk factors for predicting malignancy in atypical gastric glands during forceps biopsy. Methods: We retrospectively reviewed medical records of 252 patients with a diagnosis of atypical gastric gland during forceps biopsy. Predictors of malignancy were analyzed using initial endoscopic findings and clinical data. Results: The final diagnosis for 252 consecutive patients was gastric cancer in 189 (75%), adenoma in 26 (10.3%), and gastritis in 37 (14.7%). In the multivariate analysis, lesion sizes of more than 10 mm (odds ratio [OR], 3.021; 95% confidence interval [CI], 1.480 to 6.165; p=0.002), depressed morphology (OR, 3.181; 95% CI, 1.579 to 6.406, p=0.001), and surface nodularity (OR, 3.432; 95% CI, 1.667 to 7.064, p=0.001) were significant risk factors for malignancy. Conclusions: Further evaluation and treatment should be considered for atypical gastric gland during forceps biopsy if there is a large-sized (>10 mm) lesion, depressed morphology, or surface nodularity.


Assuntos
Adenoma/diagnóstico , Detecção Precoce de Câncer/métodos , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Biópsia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Instrumentos Cirúrgicos
20.
Sci Rep ; 8(1): 6611, 2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29700375

RESUMO

Although several epigenetic modulating drugs are suggested to target cancer stem cells (CSCs), additional identification of anti-CSC drugs is still necessary. Here we showed that JIB-04, a pan-selective inhibitor of histone demethylase(s), was identified as a small molecule that selectively target colorectal CSCs. Our data showed that JIB-04 is capable of reducing self-renewal and stemness of colorectal CSCs in three different colorectal cancer cell lines. JIB-04 significantly attenuated CSC tumorsphere formation, growth/relapse, invasion, and migration in vitro. Furthermore, JIB-04-treated colorectal cancer cells showed reduced tumorigenic activity in vivo. RNA sequencing analysis revealed that JIB-04 affected various cancer-related signaling pathways, especially Wnt/ß-catenin signaling, which is crucial for the proliferation and maintenance of colorectal cancer cells. qRT-PCR and TOP/FOP flash luciferase assays showed that JIB-04 down-regulated the expression of Wnt/ß-catenin-regulated target genes associated with colorectal CSC function. Overall, the effects of JIB-04 were equal to or greater than those of salinomycin, a known anti-colorectal CSC drug, despite the lower concentration of JIB-04 compared with that of salinomycin. Our results strongly suggest that JIB-04 is a promising drug candidate for colorectal cancer therapy.


Assuntos
Aminopiridinas/farmacologia , Neoplasias Colorretais/metabolismo , Histona Desmetilases/antagonistas & inibidores , Hidrazonas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Expressão Gênica , Humanos , Camundongos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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