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1.
BMC Gastroenterol ; 23(1): 326, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740192

RESUMO

BACKGROUND: Autophagy plays an important role in carcinogenesis and tumor progression in many cancers, including gastric cancer. Cytotoxin-associated gene A (CagA) is a well-known virulent factor in Helicobacter pylori (H. pylori) infection that plays a critical role in gastric inflammation and gastric cancer development. However, its role in autophagy during these processes remains unclear. Therefore, we aimed to clarify the role of CagA in autophagy in CagA-related inflammation. METHODS: We evaluated the autophagic index of AGS cells infected with wild-type cagA-positive H. pylori (Hp-WT) and cagA-knockout H. pylori (Hp-ΔcagA) and rat gastric mucosal (RGM1) cells transfected with CagA genes. To identify the mechanisms underlying the down regulation of autophagy in AGS cells infected with H. pylori, we evaluated protein and mRNA expression levels of autophagy core proteins using western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). To determine whether autophagy induced the expression of the pro-inflammatory mediator, cyclooxygenase-2 (COX-2), we evaluated COX-2 expression in AGS cells treated with an autophagy inducer and inhibitor and infected with H. pylori. In addition, we evaluated whether COX-2 protein expression in AGS cells influenced beclin-1 (BECN1) expression with si-RNA transfection when infected with H. pylori. RESULTS: Autophagic flux assay using chloroquine showed that autophagy in AGS cells was significantly suppressed after H. pylori infection. The autophagic index of AGS cells infected with Hp-WT was decreased significantly when compared with that in AGS cells infected with Hp-ΔcagA. The autophagic index of RGM1 cells transfected with CagA was lower, suggesting that CagA inhibits autophagy. In addition, BECN1 expression levels in AGS cells infected with Hp-WT were reduced compared to those in AGS cells infected with Hp-ΔcagA. Furthermore, COX-2 expression in AGS cells infected with H. pylori was controlled in an autophagy-dependent manner. When AGS cells were transfected with small interfering RNA specific for BECN1 and infected with Hp-WT and Hp-ΔcagA, COX-2 was upregulated significantly in cells infected with Hp-ΔcagA. CONCLUSIONS: In conclusion, the H. pylori CagA protein negatively regulated autophagy by downregulating BECN1. CagA-induced autophagy inhibition may be a causative factor in promoting pro-inflammatory mediator production in human gastric epithelial cells.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Humanos , Animais , Ratos , Neoplasias Gástricas/genética , Ciclo-Oxigenase 2/genética , Autofagia/genética , Citotoxinas , Mediadores da Inflamação
2.
J Gastroenterol Hepatol ; 38(6): 948-954, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36797208

RESUMO

BACKGROUND AND AIM: Cold snare polypectomy is commonly performed to remove small colorectal polyps. Accidental resection of carcinomas during this procedure has been reported. Herein, we aimed to clarify the clinicopathological features and clinical course of colorectal carcinomas resected by cold snare polypectomy. METHODS: This multicenter retrospective cohort study was conducted at 10 Japanese healthcare centers. Of the colorectal lesions resected by cold snare polypectomy between April 2016 and March 2020, lesions pathologically diagnosed as carcinoma were reviewed. Centralized histology (based on the Vienna classification) and endoscopic reviews were performed. The study endpoints were endoscopic features and clinical outcomes of cold snare polypectomy-resected colorectal carcinomas (Vienna category ≥4.2). RESULTS: We reviewed 74 of the 70 693 lesions resected by cold snare polypectomy. After a central pathological review, 68 lesions were diagnosed as carcinomas. The Japan Narrow-band imaging Expert Team (JNET) classification type 2B, lesion size ≥6 mm, and multinodular morphology were the significant endoscopic predictors of carcinoma resected by cold snare polypectomy. No adverse events related to the procedure occurred. Sixty-three lesions were diagnosed as carcinomas within the mucosal layer, and 34 were curative resections. Of the five carcinoma lesions with submucosal invasion, additional surgery revealed remnant cancer tissues in one lesion. No local or metastatic recurrence was observed during follow-up. CONCLUSIONS: Although most of the carcinomas resected by cold snare polypectomy were within the mucosal layer, few lesions invading the submucosa were identified. Careful pre-procedural endoscopic evaluation, especially focusing on the JNET classification and multinodular morphology, is recommended.


Assuntos
Carcinoma , Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/patologia , Colonoscopia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Colorretais/patologia , Progressão da Doença , Estudos Multicêntricos como Assunto
3.
Analyst ; 147(12): 2843-2850, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35621375

RESUMO

Raman spectroscopy is a powerful method for estimating the molecular structure of a target that can be adapted for biomedical analysis given its non-destructive nature. Inflammatory skin diseases impair the skin's barrier function and interfere with the patient's quality of life. There are limited methods for non-invasive and objective assessment of skin inflammation. We examined whether Raman spectroscopy can be used to predict skin inflammation with high sensitivity and specificity when combined with artificial intelligence (AI) analysis. Inflammation was chemically induced in mouse ears, and Raman spectra induced by a 785 nm laser were recorded. A principal component (PC) analysis of the Raman spectra was performed to extract PCs with the highest percentage of variance and to estimate the statistical score. The accuracy in predicting inflammation based on the Raman spectra with or without AI analysis was assessed using receiver operating characteristic (ROC) curves. We observed some typical changes in the Raman spectra upon skin inflammation, which may have resulted from vasodilation and interstitial oedema. The estimated statistical scores based on spectral changes correlated with the histopathological changes in the skin. The ROC curve based on PC2, which appeared to include some spectral features, revealed a maximum accuracy rate of 80.0% with an area under the curve (AUC) of 0.864. The AI analysis improved the accuracy rate to 93.1% with an AUC of 0.972. The current findings demonstrate that the combination of Raman spectroscopy with near-infrared excitation and AI analysis can provide highly accurate information on the pathology of skin inflammation.


Assuntos
Inteligência Artificial , Análise Espectral Raman , Animais , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/diagnóstico , Camundongos , Análise de Componente Principal , Qualidade de Vida , Análise Espectral Raman/métodos
4.
J Gastroenterol Hepatol ; 37(8): 1561-1570, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35435994

RESUMO

BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) induce intestinal enteropathy and the pathophysiology is related to immune-mediated mechanisms. We aimed to investigate the role of C-C chemokine receptor type 7 (CCR7) which regulates immune cell migration in NSAID-induced enteropathy. METHODS: Injury of the small intestine was evaluated 24 h after the subcutaneous injection of indomethacin in CCR7-deficient (Ccr7-/- ) and wild-type (WT) mice. The cellular profile and cytokine production in intestinal cells were analyzed. Indomethacin-induced enteropathy was evaluated in mice adoptively transferred with CD103+ dendritic cells (DCs) from Ccr7-/- or WT mice. RESULTS: Indomethacin induced more severe intestinal injury in Ccr7-/- mice than in WT mice. The major inflammatory cytokines were not increased and the proportion of regulatory T cells following indomethacin injection was not decreased in Ccr7-/- mice compared with WT mice. The expression of interleukin (IL)-22 binding protein (IL-22BP), which inhibits IL-22 activity, was significantly higher in CD103+ DCs from Ccr7-/- mice than those from WT mice. Mice adoptively transferred with CD103+ DCs isolated from Ccr7-/- mice exhibited more severe intestinal injury following indomethacin injection compared with those adoptively transferred with CD103+ DCs of WT mice. Ccr7-/- mice injected with indomethacin showed a significant reduction in regenerating islet-derived 1 (Reg1) mRNA expression, which is regulated by IL-22, in intestinal epithelial cells. CONCLUSIONS: C-C chemokine receptor type 7 deficiency exacerbated NSAID-induced enteropathy in association with an altered phenotype of CD103+ DCs that produces IL-22BP. CCR7 contributes to protect the small intestine from NSAID-induced mucosal injury.


Assuntos
Anti-Inflamatórios não Esteroides , Indometacina , Enteropatias , Receptores CCR7 , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Células Dendríticas , Indometacina/efeitos adversos , Enteropatias/induzido quimicamente , Litostatina , Camundongos , Camundongos Endogâmicos C57BL , Receptores CCR7/genética
5.
J Gastroenterol Hepatol ; 37(12): 2306-2312, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36266771

RESUMO

BACKGROUND AND AIM: Sessile serrated lesions (SSLs) act as precursors to colorectal cancer, sometimes harbor carcinomas, and are sometimes incompletely resected. We aimed to evaluate local recurrence after endoscopic resection of SSL ≥10 mm. METHODS: This prospective, single-arm, observational study was performed at eight Japanese tertiary institutions. Colorectal lesions ≥10 mm were resected endoscopically, and the pathological diagnosis was either an SSL or hyperplastic polyp (HP). Follow-up colonoscopy was performed 1 year later, and the local recurrence was evaluated by biopsy. RESULTS: From October 2018 to September 2021, 104 cases with 123 lesions were registered. Among the pathologically diagnosed 105 SSLs and 18 HPs, 95 and 7 lesions were diagnosed as SSLs and HPs, respectively, by central pathological review. Among the 104 endoscopically diagnosed SSLs, 86 were diagnosed as SSLs, whereas among the 11 endoscopically diagnosed HPs, two were diagnosed as HPs by central pathological review (the rest were SSLs). Among the 95 patients with 113 lesions who underwent follow-up colonoscopy, resection scars were identified in 95 (84%) lesions. Three (3.1%; 95% confidence interval 0.6-8.7%) local recurrences were diagnosed pathologically among 98 pathologically diagnosed SSLs. Two (6%) local recurrences were diagnosed in patients with SSLs ≥20 mm. CONCLUSIONS: The local recurrence rate after endoscopic resection of SSLs ≥10 mm was 3.1%. Careful follow-up is recommended after endoscopic resection of large SSLs. Endoscopically diagnosed HPs ≥10 mm were sometimes pathologically diagnosed as SSL and should be considered for resection.


Assuntos
Neoplasias Colorretais , Humanos , Estudos Prospectivos , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia
6.
Digestion ; 103(5): 347-356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35709705

RESUMO

INTRODUCTION: Magnifying endoscopy with narrow-band imaging (M-NBI) is useful for determining lateral demarcation of early gastric cancers; however, this is sometimes difficult. Features related to an unclear lateral demarcation remain unknown. We evaluated the clinical and histopathological features of early gastric cancers with unclear lateral demarcation on M-NBI. METHODS: This single-center, retrospective, cohort study analyzed early gastric cancer treated by endoscopic submucosal dissection between January 2013 and August 2015. We evaluated the clinicopathological and immunohistochemical features using anti-p53, anti-Ki-67, anti-MUC5AC, anti-MUC6, anti-MUC2, and anti-CD10 antibody staining. We compared the lateral demarcation between the demarcation clear (DC) and the demarcation unclear (DU) lesions by using M-NBI. RESULTS: A total of 224 differentiated adenocarcinomas (DU group: 18 lesions; DC group: 206 lesions) were analyzed. A history of successful Helicobacter pylori eradication was significantly more frequent in the DU group (p = 0.001). We examined the tissues of 72 lesions (DU group: 18 lesions, DC group: 54 lesions [randomly selected]) immunohistochemically. The nonneoplastic superficial epithelium was observed more frequently in the DU group as compared to in the DC group (p = 0.006). Additionally, compared to the DC group, the DU group showed a significantly higher expression of the gastric phenotype markers (p = 0.023) and had lower p53 scores (p < 0.001) and Ki-67 labeling indexes (p = 0.029). Multivariate analysis revealed the nonneoplastic superficial epithelium and a low p53 score as the significant independent variables associated with an unclear lateral demarcation on M-NBI. CONCLUSIONS: The nonneoplastic superficial epithelium and a low p53 score were associated with difficulties in determining the lateral demarcation in early gastric cancers on M-NBI.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Estudos de Coortes , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Humanos , Imagem de Banda Estreita/métodos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
7.
Opt Express ; 29(11): 17628-17668, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154302

RESUMO

Guided acoustic Brillouin (GAWBS) noise is measured using a novel, homodyne measurement technique for four commonly used fibers in long-distance optical transmission systems. The measurements are made with single spans and then shown to be consistent with separate multi-span long-distance measurements. The inverse dependence of the GAWBS noise on the fiber effective area is confirmed by comparing different fibers with the effective area varying between 80 µm2 and 150 µm2. The line broadening effect of the coating is observed, and the correlation between the width of the GAWBS peaks to the acoustic mode profile is confirmed. An extensive model of the GAWBS noise in long-distance fibers is presented, including corrections to some commonly repeated mistakes in previous reports. It is established through the model and verified with the measurements that the depolarized scattering caused by TR2m modes contributes twice as much to the optical noise in the orthogonal polarization to the original source, as it does to the noise in parallel polarization. Using this relationship, the polarized and depolarized contributions to the measured GAWBS noise is separated for the first time. As a result, a direct comparison between the theory and the measured GAWBS noise spectrum is shown for the first time with excellent agreement. It is confirmed that the total GAWBS noise can be calculated from fiber parameters under certain assumptions. It is predicted that the level of depolarized GAWBS noise created by the fiber may depend on the polarization diffusion length, and consequently, possible ways to reduce GAWBS noise are proposed. Using the developed theory, dependence of GAWBS noise on the location of the core is calculated to show that multi-core fibers would have a similar level of GAWBS noise no matter where their cores are positioned.

8.
J Gastroenterol Hepatol ; 36(8): 2239-2246, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33694189

RESUMO

BACKGROUND AND AIM: The morphological diagnosis of microvessels on the surface of superficial esophageal squamous cell carcinomas using magnifying endoscopy with narrow-band imaging is widely used in clinical practice. Nevertheless, inconsistency, even among experts, remains a problem. We constructed a convolutional neural network-based computer-aided diagnosis system to classify the microvessels of superficial esophageal squamous cell carcinomas and evaluated its diagnostic performance. METHODS: In this retrospective study, a cropped magnifying endoscopy with narrow-band images from superficial esophageal squamous cell carcinoma lesions was used as the dataset. All images were assessed by three experts, and classified into three classes, Type B1, B2, and B3, based on the Japan Esophagus Society classification. The dataset was divided into training and validation datasets. A convolutional neural network model (ResNeXt-101) was trained and tuned with the training dataset. To evaluate diagnostic accuracy, the validation dataset was assessed by the computer-aided diagnosis system and eight endoscopists. RESULTS: In total, 1777 and 747 cropped images (total, 393 lesions) were included in the training and validation datasets, respectively. The diagnosis system took 20.3 s to evaluate the 747 images in the validation dataset. The microvessel classification accuracy of the computer-aided diagnosis system was 84.2%, which was higher than the average of the eight endoscopists (77.8%, P < 0.001). The area under the receiver operating characteristic curves for diagnosing Type B1, B2, and B3 vessels were 0.969, 0.948, and 0.973, respectively. CONCLUSIONS: The computer-aided diagnosis system showed remarkable performance in the classification of microvessels on superficial esophageal squamous cell carcinomas.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Esofagoscopia , Humanos , Microvasos/diagnóstico por imagem , Redes Neurais de Computação , Estudos Retrospectivos
9.
Photochem Photobiol Sci ; 19(1): 29-33, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31932832

RESUMO

We demonstrate amyloid fibril (AF) decomposition induced by NIR-active upconversion nanoparticles complexed with photosensitisers. The process is triggered by upconversion, which initiates a photochemical reaction cascade that culminates in the generation of the highly reactive singlet-oxygen product 1O2 close to the amyloid superstructures, resulting in AF decomposition.


Assuntos
Amiloide/antagonistas & inibidores , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Amiloide/metabolismo , Humanos , Raios Infravermelhos
10.
Cancer Sci ; 110(8): 2396-2407, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148360

RESUMO

The tumor microenvironment offers favorable conditions for tumor progression, and activated fibroblasts, known as cancer-associated fibroblasts, play a pivotal role. TP53-deficient cancer cells are known to induce strong fibroblast activation. We aimed to elucidate the oncogenic role of exosomes derived from TP53-deficient colon cancer cells in fibroblast proliferation and tumor growth. Cancer cell-derived exosomes (CDEs) were isolated from the conditioned media of cancer cells using a sequential ultracentrifugation method. The effects of exosomes on tumor growth were evaluated using human cell lines (TP53-WT colon cancer, HCT116; TP53-mutant colon cancer, HT29; and fibroblasts, CCD-18Co and WI-38) and an immune-deficient nude mouse xenograft model. HCT116 (HCT116sh p53 ) cells deficient in TP53 accelerated cocultured fibroblast proliferation compared to TP53-WT HCT116 (HCT116sh control ) cells in vitro. Exosomes from HCT116sh p53 cells suppressed TP53 expression of fibroblasts and promoted their proliferation. Xenografts of HCT116sh p53 cells grew significantly faster than those of HCT116sh control cells in the presence of co-injected fibroblasts, but this difference was diminished by CDE inhibition. Microarray analysis identified upregulation of several microRNAs (miR-1249-5p, miR-6737-5p, and miR-6819-5p) in TP53-deficient CDEs, which were functionally proven to suppress TP53 expression in fibroblasts. Exosomes derived from TP53-mutant HT29 cells also suppressed TP53 expression in fibroblasts and accelerated their growth. The proliferative effect of HT29 on cocultured fibroblasts was diminished by inhibition of these miRNAs in fibroblasts. Our results suggest that CDEs play a pivotal role in tumor progression by fibroblast modification. Cancer cell-derived exosomes might, therefore, represent a novel therapeutic target in colon cancer.


Assuntos
Neoplasias do Colo/genética , Exossomos/genética , MicroRNAs/genética , Proteína Supressora de Tumor p53/genética , Animais , Fibroblastos Associados a Câncer/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Colo/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HT29 , Xenoenxertos/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genética , Microambiente Tumoral/genética , Regulação para Cima/genética
12.
PLoS One ; 18(8): e0288463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37594942

RESUMO

This study aimed to investigate the bleeding risk associated with percutaneous transhepatic gallbladder interventions in patients with acute cholecystitis receiving antithrombotic therapy. In this retrospective study, 194 consecutive patients who underwent percutaneous transhepatic gallbladder interventions for acute cholecystitis between April 2011 and April 2021 were enrolled. Patients were sorted into four groups: no prior antithrombotic therapy, discontinued antithrombotic drugs, single antithrombotic drug continued perioperatively, and multiple antithrombotic drugs continued perioperatively. The risk of postoperative bleeding after percutaneous transhepatic gallbladder interventions was evaluated via multivariate logistic regression analysis. Of the 116 (59.8%) patients receiving antithrombotic therapy, 32 (16.5%) discontinued antithrombotic drugs before their respective procedure, 50 (25.8%) continued a single antithrombotic drug, and 34 (17.5%) continued multiple antithrombotic drugs during the perioperative period. The rates of significant and severe bleeding were 10.3% (20/194) and 3.1% (6/194), respectively. The rate of significant bleeding was significantly higher in patients who continued multiple antithrombotic drugs than in patients who received no prior antithrombotic therapy (P = 0.006). In the multivariate logistic regression analysis, the continuation of multiple antithrombotic drugs during the perioperative period was a risk factor for significant bleeding after percutaneous transhepatic gallbladder interventions. In conclusion, the perioperative continuation of multiple antithrombotic drugs is a risk factor for postoperative bleeding after percutaneous transhepatic gallbladder interventions.


Assuntos
Colecistite Aguda , Fibrinolíticos , Humanos , Fibrinolíticos/efeitos adversos , Estudos Retrospectivos , Hemorragia Pós-Operatória/etiologia , Drenagem
13.
Int J Oncol ; 63(6)2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37921070

RESUMO

Cancer­associated fibroblasts (CAFs) are pivotal in tumor progression. TP53­deficiency in cancer cells is associated with robust stromal activation. The apelin­apelin receptor (APJ) system has been implicated in suppressing fibroblast­to­myofibroblast transition in non­neoplastic organ fibrosis. The present study aimed to elucidate the oncogenic role of the apelin­APJ system in tumor fibroblasts. APJ expression and the effect of APJ suppression in fibroblasts were investigated for p53 status in cancer cells using human cell lines (TP53­wild colon cancer, HCT116, and Caco­2; TP53­mutant colon cancer, SW480, and DLD­1; and colon fibroblasts, CCD­18Co), resected human tissue samples of colorectal cancers, and immune­deficient nude mouse xenograft models. The role of exosomes collected by ultracentrifugation were also analyzed as mediators of p53 expression in cancer cells and APJ expression in fibroblasts. APJ expression in fibroblasts co­cultured with p53­suppressed colon cancer cells (HCT116sh p53 cells) was significantly lower than in control colon cancer cells (HCT116sh control cells). APJ­suppressed fibroblasts treated with an antagonist or small interfering RNA showed myofibroblast­like properties, including increased proliferation and migratory abilities, via accelerated phosphorylation of Sma­ and Mad­related protein 2/3 (Smad2/3). In addition, xenografts of HCT116 cells with APJ­suppressed fibroblasts showed accelerated tumor growth. By contrast, apelin suppressed the upregulation of phosphorylated Smad2/3 in fibroblasts. MicroRNA 5703 enriched in exosomes derived from HCT116sh p53 cells inhibited APJ expression, and inhibition of miR­5703 diminished APJ suppression in fibroblasts caused by cancer cells. APJ suppression from a specific microRNA in cancer cell­derived exosomes induced CAF­like properties in fibroblasts. Thus, the APJ system in fibroblasts in the tumor microenvironment may be a promising therapeutic target.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias do Colo , MicroRNAs , Camundongos , Animais , Humanos , Receptores de Apelina/genética , Receptores de Apelina/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Células CACO-2 , Apelina/genética , Apelina/metabolismo , Fibroblastos/metabolismo , MicroRNAs/genética , Neoplasias do Colo/patologia , Transdução de Sinais , Fibroblastos Associados a Câncer/metabolismo , Proliferação de Células , Microambiente Tumoral
14.
Phys Chem Chem Phys ; 13(40): 18031-7, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-21922093

RESUMO

Artificial photosynthesis is one of the chemists' dreams and the separation of charges with long lives is fundamental for achieving artificial photosynthesis. In actual photosynthesis, Z-scheme excitation separates electronic charge with high efficiency using solar light. Here we report that photo-excitation in Cr-tetraphenylporphyrin chroride (Cr-TPPCl)/Zr doped KTaO(3) (KTa(Zr)O(3)) is analogous to the Z-scheme in photosynthesis, and that we achieve complete charge separation at room temperature. Photovoltaic decay and transient fluorescence spectra measurements showed that the photo-excited charge in KTa(Zr)O(3) transferred to the HOMO of Cr-TPPCl within a few hundred pico-seconds on charge transfer. In contrast, the reduced state of the Cr-TPPCl species that was formed by the electronic injection from KTa(Zr)O(3) was observed for more than 0.5 s at room temperature in the transient decay of the absorption spectra change after the initial excitation of KTa(Zr)O(3). The formed reduced state of Cr-TPPCl was highly stable and was detected by static ESR measurements.


Assuntos
Óxidos/química , Fotossíntese , Porfirinas/química , Potássio/química , Tantálio/química , Água/química , Catálise , Cromo/química , Transporte de Elétrons , Zircônio/química
15.
Sci Rep ; 11(1): 19524, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593902

RESUMO

Deficiency of p53 in cancer cells activates the transformation of normal tissue fibroblasts into carcinoma-associated fibroblasts; this promotes tumor progression through a variety of mechanisms in the tumor microenvironment. The role of autophagy in carcinoma-associated fibroblasts in tumor progression has not been elucidated. We aimed to clarify the significance of autophagy in fibroblasts, focusing on the TP53 status in co-cultured human colorectal cancer cell lines (TP53-wild-type colon cancer, HCT116; TP53-mutant colon cancer, HT29; fibroblast, CCD-18Co) in vitro. Autophagy in fibroblasts was significantly suppressed in association with ACTA2, CXCL12, TGFß1, VEGFA, FGF2, and PDGFRA mRNA levels, when co-cultured with p53-deficient HCT116sh p53 cells. Exosomes isolated from the culture media of HCT116sh p53 cells significantly suppressed autophagy in fibroblasts via inhibition of ATG2B. Exosomes derived from TP53-mutant HT29 cells also suppressed autophagy in fibroblasts. miR-4534, extracted from the exosomes of HCT116sh p53 cells, suppressed ATG2B in fibroblasts. In conclusion, a loss of p53 function in colon cancer cells promotes the activation of surrounding fibroblasts through the suppression of autophagy. Exosomal miRNAs derived from cancer cells may play a pivotal role in the suppression of autophagy.


Assuntos
Autofagia/genética , Fibroblastos Associados a Câncer/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteína Supressora de Tumor p53/deficiência , Proteínas Relacionadas à Autofagia/metabolismo , Biomarcadores Tumorais , Linhagem Celular Tumoral , Células Cultivadas , Técnicas de Cocultura , Neoplasias Colorretais/patologia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , MicroRNAs/genética , Modelos Biológicos , Microambiente Tumoral/genética , Proteínas de Transporte Vesicular/metabolismo
16.
JGH Open ; 4(2): 178-184, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32280762

RESUMO

BACKGROUND AND AIM: To investigate whether assessment by magnifying narrow-band imaging (M-NBI) based on the classification of the Japan Esophageal Society provides additional value to the estimation of the invasion depth of superficial esophageal squamous cell carcinoma (SCC) compared with assessment by white light endoscopy (WLE) alone. METHODS: Endoscopic images of 211 consecutive superficial esophageal SCCs resected by endoscopic submucosal dissection were separated into WLE and M-NBI images. Depth estimation was performed independently by five evaluators using the numerical depth estimation scale (0 = epithelium (EP)/lamina propria (LPM), 1 = EP/LPM > muscularis mucosa (MM)/shallow submucosa (SM1), 2 = MM/SM1 > EP/LPM, 3 = MM/SM1, 4 = MM/SM1 > deep submucosa (SM2), 5 = SM2 > MM/SM1, 6 = SM2), using primarily WLE images (step 1), and subsequently both WLE and M-NBI images (step 2). The discordance scores, determined by the average of the five evaluators' difference between the estimated score (from 0 to 6) and pathological score (0 for histologically proven EP/LPM, 3 for MM/SM1, and 6 for SM2), were analyzed in steps 1 and 2. RESULTS: The discordance scores significantly decreased in step 2 (0.53 ± 0.06) compared with those in step 1 (0.79 ± 0.07) (P < 0.001). When the discordance score < 1.5 was regarded as a clinically correct diagnosis, the rate of the clinically correct diagnosis significantly increased in step 2 compared with that in step 1 (81% to 91%, P < 0.001). CONCLUSION: M-NBI has an additive value for estimating the invasion depth of superficial esophageal SCCs.

17.
Endosc Int Open ; 8(4): E536-E543, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32258376

RESUMO

Background and study aims Patients with esophageal squamous cell carcinoma (SCC) are at high risk of developing second primary SCCs in the hypopharynx. However, such second primary tumors are difficult to observe because of lumen closure. The Valsalva maneuver using a dedicated mouthpiece is a promising technique to visualize the hypopharynx during transoral endoscopy. In the current study, we investigated the utility of this method. Patients and methods The current study was a randomized, controlled, crossover trial. Patients with esophageal SCC were randomly assigned first to undergo pharyngeal observation using the dedicated mouthpiece followed by observation using a conventional mouthpiece, or vice versa. The primary endpoint was complete visualization of the hypopharynx, which was assessed blindly by three external evaluators. Results A total of 68 pharyngeal examinations were analyzed - 34 with the dedicated mouthpiece and 34 with a conventional mouthpiece. Complete visualization was achieved in 68 % of the examinations (23/34) using the dedicated mouthpiece, whereas none of the examinations using the conventional mouthpiece achieved complete visualization of the hypopharynx. Observation scores of the oropharynx were not significantly different between both types of examination ( P  = 0.50). No serious adverse events (AEs) occurred. Conclusions Endoscopic view of the hypopharynx was markedly improved by the Valsalva maneuver using the dedicated mouthpiece, with no serious AEs. This procedure should be included in the endoscopic examinations for the patients with esophageal SCCs.

18.
Chemistry ; 15(46): 12862-70, 2009 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-19834939

RESUMO

The mechanism of photocatalytic splitting of H(2)O into H(2) and O(2) on Pt/KTa(Zr)O(3) modified with various porphyrinoids was investigated. The photocatalytic activity of KTaO(3) catalysts is improved by dye modification. Cyanocobalamin (vitamin B(12)) is the most effective for improving water-splitting activity, and the formation rates of H(2) and O(2) achieved values of 575 and 280 micromol g(cat.) (-1) h(-1), respectively. X-ray photoelectron spectroscopy spectra of KTa(Zr)O(3) photocatalysts showed that Pt loaded onto dye-modified KTaO(3) was slightly oxidized and had low catalytic activity for the H(2) oxidation reaction. Photoluminescence (PL) spectra of KTaO(3) catalysts suggested that excitation energy was transferred between KTaO(3), tetraphenylporphyrinatochromium(III) (Cr-TPP), and the Pt cocatalyst. The wavelength dependence of the activity of dye-modified KTa(Zr)O(3) photocatalysts indicated that excitation of both KTa(Zr)O(3) and the dye was essential for achieving increased photocatalytic activity. This result suggests that two-step excitation occurred in the dye-modified KTa(Zr)O(3) photocatalysts. Because the lifetime of the charge-separated state increased, this study reveals that modification with porphyrinoids is effective for increasing water-splitting activity.

19.
Nat Commun ; 10(1): 3033, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292442

RESUMO

Fiber nonlinearity is one of the major limitations to the achievable capacity in long distance fiber optic transmission systems. Nonlinear impairments are determined by the signal pattern and the transmission system parameters. Deterministic algorithms based on approximating the nonlinear Schrodinger equation through digital back propagation, or a single step approach based on perturbation methods have been demonstrated, however, their implementation demands excessive signal processing resources, and accurate knowledge of the transmission system. A completely different approach uses machine learning algorithms to learn from the received data itself to figure out the nonlinear impairment. In this work, a single-step, system agnostic nonlinearity compensation algorithm based on a neural network is proposed to pre-distort symbols at transmitter side to demonstrate ~0.6 dB Q improvement after 2800 km standard single-mode fiber transmission using 32 Gbaud signal. Without prior knowledge of the transmission system, the neural network tensor weights are constructed from training data thanks to the intra-channel cross-phase modulation and intra-channel four-wave mixing triplets used as input features.

20.
Tissue Eng Part A ; 19(1-2): 24-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22839964

RESUMO

Regenerative therapy using stem cells is a promising approach for the treatment of stroke. Recently, we reported that dental pulp stem cells (DPSC) ameliorated ischemic tissue injury in the rat brain and accelerated functional recovery after middle cerebral artery occlusion (MCAO). In this study, we investigated the effects of stem cells from human exfoliated deciduous tooth (SHED)-derived conditioned medium (SHED-CM) on permanent MCAO (pMCAO). Adult male Sprague-Dawley rats were subjected to pMCAO. SHED-CM were then administered intranasally, and the motor function and infarct volume were evaluated. Neurogenesis and vasculogenesis were determined using immunochemical markers. The SHED-CM group had more positive signals than the Dulbecco's modified Eagle's medium group, with doublecortin (DCX), neurofilament H, neuronal nuclei, and rat endothelial cell antigen observed in the peri-infarct area. Migration of neuronal progenitor cells (NPC) with DCX from the subventricular zone to the peri-infarct area was observed on days 6 and 16, with migration on day 6 being the most prominent. In conclusion, SHED-CM promoted the migration and differentiation of endogenous NPC, induced vasculogenesis, and ameliorated ischemic brain injury after pMCAO as well as transplantation of DPSC.


Assuntos
Isquemia Encefálica/patologia , Isquemia Encefálica/cirurgia , Transplante de Células-Tronco/métodos , Dente Decíduo/citologia , Dente Decíduo/transplante , Animais , Proteína Duplacortina , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Resultado do Tratamento
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