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1.
ACS Appl Mater Interfaces ; 15(40): 46849-46860, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37773933

RESUMO

A crystalline silicon (c-Si) solar cell with a polycrystalline silicon/SiOx (poly-Si/SiOx) structure, incorporating both electron and hole contacts, is an attractive choice for achieving ideal carrier selectivity and serving as a fundamental component in high-efficiency perovskite/Si tandem and interdigitated back-contact solar cells. However, our understanding of the carrier transport mechanism of hole contacts remains limited owing to insufficient studies dedicated to its investigation. There is also a lack of comparative studies on the poly-Si/SiOx electron and hole contacts for ideal carrier-selective solar cells. Therefore, this study aims to address these knowledge gaps by exploring the relationship among microstructural evolution, dopant in-diffusion, and the resulting carrier transport mechanism in both the electron and hole contacts of poly-Si/SiOx solar cells. Electron (n+ poly-Si/SiOx/substrate)- and hole (p+ poly-Si/SiOx/substrate)-selective passivating contacts are subjected to thermal annealing. Changes in the passivation properties and carrier transport mechanisms of these contacts are investigated during thermal annealing at various temperatures. Notably, the results demonstrate that the passivation properties and carrier transport mechanisms are strongly influenced by the microstructural evolution of the poly-Si/SiOx layer stack and dopant in-diffusion. Furthermore, electron and hole contacts exhibit common behaviors regarding microstructural evolution and dopant in-diffusion. However, the hole contacts exhibit relatively inferior electrical properties overall, mainly because both the SiOx interface and the p+ poly-Si are found to be highly defective. Moreover, boron in the hole contacts diffuses deeper than phosphorus in the electron contacts, resulting in deteriorated carrier collection. The experimental results are also supported by device simulation. Based on these findings, design rules are suggested for both electron and hole contacts, such as using thicker SiOx and/or annealing the solar cell at a temperature not exceeding the critical annealing temperature of the hole contacts.

2.
Ann Occup Environ Med ; 35: e22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37614336

RESUMO

Background: Shift work increases the risk of chronic diseases, including metabolic diseases. However, studies on the relationship between shift work and renal function are limited. The aim of this study was to investigate the association between shift work and a decreased glomerular filtration rate (GFR). Methods: Data were evaluated for 1,324,930 workers who visited the Korean Medical Institute from January 1, 2016 to December 31, 2020 and underwent a health checkup. Daytime workers were randomly extracted at a ratio of 1:4 after matching for age and sex. In total, 18,190 workers aged over 40 years were included in the analyses; these included 3,638 shift workers and 14,552 daytime workers. Participants were categorized into the shift work group when they underwent a specific health checkup for night shift work or indicated that they were shift workers in the questionnaire. The odds ratio was calculated using a conditional logistic regression to investigate the relevance of shift work for changes in GFR. Results: 35 workers in the shift group and 54 in the daytime group exhibited an estimated GFR (eGFR) value of < 60 mL/min/1.73m2 (p < 0.01). The difference in eGFR values between two checkups differed significantly depending on the type of work (p < 0.01); the difference in the shift work group (-9.64 mL/min/1.73 m2) was larger than that in the daytime work group (-7.45 mL/min/1.73 m2). The odds ratio for eGFR reduction to < 60 mL/min/1.73 m2 in the shift group versus the daytime group was 4.07 (95% confidence interval: 2.54-6.52), which was statistically significant. Conclusions: The results of this study suggest that eGFR decreases by a significantly larger value in shift workers than in daytime workers; thus, shift work could be a contributing factor for chronic kidney disease (CKD). Further prospective studies are necessary to validate this finding and identify measures to prevent CKD in shift workers.

3.
J Clin Sleep Med ; 19(2): 327-337, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36271597

RESUMO

STUDY OBJECTIVES: Information on obstructive sleep apnea (OSA) is often latently detected in diagnostic tests conducted for other purposes, providing opportunities for maximizing value. This study aimed to develop a convolutional neural network (CNN) to identify the risk of OSA using lateral cephalograms. METHODS: The lateral cephalograms of 5,648 individuals (mean age, 49.0 ± 15.8 years; men, 62.3%) with or without OSA were collected and divided into training, validation, and internal test datasets in a 5:2:3 ratio. A separate external test dataset (n = 378) was used. A densely connected CNN was trained to diagnose OSA using a cephalogram. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Gradient-weighted class activation mapping (Grad-CAM) was used to evaluate the region of focus, and the relationships between the model outputs, anthropometric characteristics, and OSA severity were evaluated. RESULTS: The AUROC of the model for the presence of OSA was 0.82 (95% confidence interval, 0.80-0.84) and 0.73 (95% confidence interval, 0.65-0.81) in the internal and external test datasets, respectively. Grad-CAM demonstrated that the model focused on the area of the tongue base and oropharynx in the cephalogram. Sigmoid output values were positively correlated with OSA severity, body mass index, and neck and waist circumference. CONCLUSIONS: Deep learning may help develop a model that classifies OSA using a cephalogram, which may be clinically useful in the appropriate context. The definition of ground truth was the main limitation of this study. CITATION: Jeong H-G, Kim T, Hong JE, et al. Automated deep neural network analysis of lateral cephalogram data can aid in detecting obstructive sleep apnea. J Clin Sleep Med. 2023;19(2):327-337.


Assuntos
Apneia Obstrutiva do Sono , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/diagnóstico , Antropometria , Redes Neurais de Computação , Índice de Massa Corporal , Circunferência da Cintura
4.
Sci Rep ; 12(1): 20998, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470931

RESUMO

Differential diagnosis of left ventricular hypertrophy (LVH) is often obscure on echocardiography and requires numerous additional tests. We aimed to develop a deep learning algorithm to aid in the differentiation of common etiologies of LVH (i.e. hypertensive heart disease [HHD], hypertrophic cardiomyopathy [HCM], and light-chain cardiac amyloidosis [ALCA]) on echocardiographic images. Echocardiograms in 5 standard views (parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 3-chamber) were obtained from 930 subjects: 112 with HHD, 191 with HCM, 81 with ALCA and 546 normal subjects. The study population was divided into training (n = 620), validation (n = 155), and test sets (n = 155). A convolutional neural network-long short-term memory (CNN-LSTM) algorithm was constructed to independently classify the 3 diagnoses on each view, and the final diagnosis was made by an aggregate network based on the simultaneously predicted probabilities of HCM, HCM, and ALCA. Diagnostic performance of the algorithm was evaluated by the area under the receiver operating characteristic curve (AUC), and accuracy was evaluated by the confusion matrix. The deep learning algorithm was trained and verified using the training and validation sets, respectively. In the test set, the average AUC across the five standard views was 0.962, 0.982 and 0.996 for HHD, HCM and CA, respectively. The overall diagnostic accuracy was significantly higher for the deep learning algorithm (92.3%) than for echocardiography specialists (80.0% and 80.6%). In the present study, we developed a deep learning algorithm for the differential diagnosis of 3 common LVH etiologies (HHD, HCM and ALCA) by applying a hybrid CNN-LSTM model and aggregate network to standard echocardiographic images. The high diagnostic performance of our deep learning algorithm suggests that the use of deep learning can improve the diagnostic process in patients with LVH.


Assuntos
Cardiomiopatia Hipertrófica , Cardiopatias , Hipertensão , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Diagnóstico Diferencial , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/complicações , Ecocardiografia/efeitos adversos , Cardiopatias/diagnóstico , Redes Neurais de Computação
5.
Adv Mater ; 33(41): e2103708, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34476855

RESUMO

The fabrication of ultrathin silicon wafers at low cost is crucial for advancing silicon electronics toward stretchability and flexibility. However, conventional fabrication techniques are inefficient because they sacrifice a large amount of substrate material. Thus, advanced silicon electronics that have been realized in laboratories cannot move forward to commercialization. Here, a fully bottom-up technique for producing a self-releasing ultrathin silicon wafer without sacrificing any of the substrate is presented. The key to this approach is a self-organized nanogap on the substrate fabricated by plasma-assisted epitaxial growth (plasma-epi) and subsequent hydrogen annealing. The wafer thickness can be independently controlled during the bulk growth after the formation of plasma-epi seed layer. In addition, semiconductor devices are realized using the ultrathin silicon wafer. Given the high scalability of plasma-epi and its compatibility with conventional semiconductor process, the proposed bottom-up wafer fabrication process will open a new route to developing advanced silicon electronics.

6.
Antioxidants (Basel) ; 9(12)2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33291466

RESUMO

In this study, potential protection of chlorophyll a from illumination and oxidation-induced decomposition has been examined using C-phycocyanin (C-PC) aqueous medium. Photo-oxidation resistance of chlorophyll a was monitored in various aqueous media using ultraviolet-visible spectroscopy and direct-infusion atmospheric pressure chemical ionization mass spectrometry analysis. The spectroscopy results showed that chlorophyll a in C-PC medium experienced the lowest rate of conversion to its derivatives; thus, it was demonstrated that chlorophyll a was mostly intact in the C-PC medium. Furthermore, the C-PC treated with chlorophyll a showed the lowest concentrations of malondialdehyde, and chlorophyll a in C-PC medium did not cause serious damage to human liver cells in vitro after intensive illumination. Therefore, we propose a new method of protecting chlorophyll a from photodegradation and oxidation using C-PC aqueous medium.

7.
Medicine (Baltimore) ; 99(2): e18565, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914034

RESUMO

BACKGROUND: Atopic dermatitis (AD, atopic eczema) is a pruritic, inflammatory, chronic skin disease. Since there is limitation of conventional treatment of AD, traditional herbal medicine can be an attractive therapeutic option in patients having AD for a long time. So-Cheong-Ryong-Tang (SCRT) has been found to inhibit histamine release and degranulation of mast cells, differentiation of basophils, and proliferation of eosinophils. We designed this clinical trial to evaluate the efficacy and safety of SCRT as compared to placebo in patients with AD and respiratory disorders. METHODS/DESIGN: This study is a single-center, randomized, double-blind, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients between 7 and 65 years of age with AD and respiratory disorders who received a diagnosis of AD by Hanifin and Rajka criteria who scored 15 to 50 in a scoring atopic dermatitis (SCORAD) will be enrolled. Participants will be randomly assigned to the SCRT or placebo group in a ratio of 1:1 and they will have a visit schedule comprising 4 visits including a screening visit during 8 to 10 weeks. The participants will be administered SCRT or placebo 3 times a day for 4 weeks. The primary outcome will be measured by a change of the SCORAD index. The secondary outcomes will be measured by changes in the dose and frequency of usage of the AD ointment, dermatology life quality index scores, pruritus and sleep disorder in visual analog scale, skin moisture content, skin surface temperature, Hamilton anxiety rating scale scores, depression rating scale scores, stress/autonomic nervous function test, and attention deficit hyperactivity disorder survey scores at week 4 as compared to those at the baseline. DISCUSSION: To the best of our knowledge, SCRT has rarely been reported for dermatologic diseases. This will be the first clinical trial to assess the efficacy and safety of SCRT in patients with AD and respiratory disorders. We hope that the results of this trial will provide evidence for the use of SCRT as a new treatment for AD with respiratory disorders. TRIAL REGISTRATION: Korean National Clinical Trial Registry, Clinical Research Information Service. (KCT0004148) (https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=14981<ype=&rtype=).


Assuntos
Dermatite Atópica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Transtornos Respiratórios/tratamento farmacológico , Transtornos Respiratórios/epidemiologia , Adolescente , Adulto , Idoso , Criança , Depressão/epidemiologia , Dermatite Atópica/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/epidemiologia , Qualidade de Vida , Pele/fisiopatologia , Transtornos do Sono-Vigília/epidemiologia , Estresse Psicológico/epidemiologia , Adulto Jovem
8.
Medicine (Baltimore) ; 98(29): e16527, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335732

RESUMO

INTRODUCTION: Several studies have found that obesity is associated with atopic dermatitis (AD); however, the mechanisms underlying the association are largely unknown. This study aims to assess the association of AD with obesity in the Korean population and verify its mechanism via a multi-omics analysis. METHODS AND ANALYSIS: A case-control study will be conducted in the Republic of Korea. A total of 80 subjects, aged 4 to 12 years, matched for age and sex, with body mass index at or above the 85th percentile or at or below the 25th percentile, will be included. Subjects will be assigned to the following 4 groups: obese/overweight with AD, normal/underweight with AD, obese/overweight control, and normal/underweight control. Serum metabolome and immune biomarkers, as well as fecal metabolome and microbiome biomarkers, will be analyzed. Serum eosinophil cationic protein, total serum Immunoglobulin E (IgE), and specific IgE will be analyzed to assess allergic tendency. The SCORing of AD index, the children's dermatology life quality index, body composition analysis, and the Korean gastrointestinal symptom rating scale will be obtained to assess the disease status and severity of the subjects. DISCUSSION: The findings of this study are expected to provide evidence of an association between AD and obesity via a gut microbiome-metabolome-immune mechanism. Therefore, it may improve future management strategies for AD. TRIAL REGISTRATION: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0003630).


Assuntos
Dermatite Atópica/complicações , Dermatite Atópica/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Proteína Catiônica de Eosinófilo/sangue , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Imunoglobulina E/sangue , Masculino , Metaboloma , Obesidade/imunologia , Obesidade/microbiologia , Qualidade de Vida , República da Coreia
9.
Medicine (Baltimore) ; 98(18): e15479, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045830

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease that affects the quality of life in patients with AD. Since there is limitation of conventional treatment of AD, complementary treatment is required to treat AD symptoms more effectively and safely Soshiho-tang (SSHT) is a traditional herbal medicine that exhibits anti-inflammatory and anti-ulcer effects and improves the immune function. In this clinical trial, we will evaluate the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders in comparison with placebo. METHODS/DESIGN: This study is a single-center, randomized, double-blind, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients aged 3 to 18 years with AD and gastrointestinal disorders and who received a diagnosis of AD by Hanifin & Rajka criteria with a Scoring Atopic Dermatitis (SCORAD) index between 15 and 49 will be enrolled. Participants will be randomly assigned to the SSHT or placebo group in a ratio of 1:1. Additionally, they will have a visit schedule comprising 4 visits including a screening visit during 8 to 10 weeks. The participants will be administered SSHT or placebo 3 times a day for 4 weeks. The primary outcome will be measured by a change of the SCORAD index. The secondary outcome measures include the following: survey questionnaires for the perception of gastrointestinal disorders, amount and frequency of ointment usage for AD, dermatology quality of life index, itchiness and sleep disability score in visual analog scale, percutaneous water loss, skin surface temperature, Hamilton anxiety rating scale, and children's depression inventory. DISCUSSION: In our knowledge, this will be the first clinical trial to assess the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders. The findings of this study will provide new treatment options for patients with AD and gastrointestinal disorders. TRIAL REGISTRATION: Korean National Clinical Trial Registry, Clinical Research Information Service. (KCT0003713) https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=13489<ype=&rtype=.


Assuntos
Dermatite Atópica/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Pomadas/uso terapêutico , Extratos Vegetais/uso terapêutico , Adolescente , Criança , Pré-Escolar , Dermatite Atópica/complicações , Método Duplo-Cego , Feminino , Gastroenteropatias/complicações , Humanos , Masculino , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Front Microbiol ; 10: 447, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930867

RESUMO

Respiratory syncytial virus (RSV) is a major pathogen that infects lower respiratory tract and causes a common respiratory disease. Despite serious pathological consequences with this virus, effective treatments for controlling RSV infection remain unsolved, along with poor innate immune responses induced at the initial stage of RSV infection. Such a poor innate defense mechanism against RSV leads us to study the role of alveolar macrophage (AM) that is one of the primary innate immune cell types in the respiratory tract and may contribute to protective responses against RSV infection. As an effective strategy for enhancing anti-viral function of AM, this study suggests the intranasal administration of Bacillus subtilis spore which induces expansion of AM in the lung with activation and enhanced production of inflammatory cytokines along with several genes associated with M1 macrophage differentiation. Such effect by spore on AM was largely dependent on TLR-MyD88 signaling and, most importantly, resulted in a profound reduction of viral titers and pathological lung injury upon RSV infection. Taken together, our results suggest a protective role of AM in RSV infection and its functional modulation by B. subtilis spore, which may be a useful and potential therapeutic approach against RSV.

11.
Cancer Res Treat ; 49(4): 915-926, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28052650

RESUMO

PURPOSE: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. MATERIALS AND METHODS: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. RESULTS: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023). CONCLUSION: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Adulto , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Biópsia , Carboplatina/farmacologia , Carcinoma Epitelial do Ovário , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Instabilidade Genômica , Xenoenxertos , Humanos , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Paclitaxel/farmacologia , Pesquisa Translacional Biomédica , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Cancer Res Treat ; 49(3): 595-606, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27669706

RESUMO

PURPOSE: This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer. MATERIALS AND METHODS: The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively. RESULTS: Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05). CONCLUSION: V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Paclitaxel/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Bombas de Próton/metabolismo , Neoplasias do Colo do Útero/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Sinergismo Farmacológico , Esomeprazol/farmacologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Paclitaxel/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Bombas de Próton/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , ATPases Vacuolares Próton-Translocadoras/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo
13.
Anticancer Res ; 36(12): 6381-6388, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27919959

RESUMO

AIM: We investigated the feasibility of dynamin 2 as a potential treatment target in cervical cancer cells. MATERIALS AND METHODS: We performed tissue microarray for dynamin 2 expression in 208 patients with early cervical cancer and in vitro in HeLa cells with dynamin 2 inhibitors MiTMAB, OcTMAB, Dynasore, and DD-6. RESULTS: Tumor size greater than 2 cm or tumor invasion of more than half of the entire cervix was associated with expression of dynamin 2 compared to no expression (p=0.013, and p=0.045, respectively). All dynamin 2 inhibitors significantly reduced proliferation, increased apoptotic activity, and reduced matrix metallopeptidase 9 expression in HeLa cells. Dynasore and DD-6 reduced migration of HeLa cells on laminin 1-coated plates and DD-6 most strongly reduced migration performance on fibronectin-coated plates. CONCLUSION: Targeting dynamin 2 may be a promising new approach for the treatment of cervical cancer.


Assuntos
Antineoplásicos/uso terapêutico , Dinamina II/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Feminino , Células HeLa , Humanos
14.
Arch Pharm Res ; 39(5): 721-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27025376

RESUMO

The purpose of this study was to evaluate the enhancing potency of tectochrysin, a flavonoid isolated from Alpinia oxyphylla Miquel by combining cetuximab, an anti-EGFR monoclonal antibody, on human colon cancer cell growth through further inhibition of EGFR pathway. HCT116 and SW480 colon cancer cells were treated with cetuximab (30 µg/mL, 1/10 of IC50), tectochrysin (5 µg/mL, 1/3 of IC50), or the combination of both agents. The growth inhibitory effect was examined using the MTT assay while apoptotic cell death was performed using TUNEL staining assays. The DNA binding activity of NF-kappa B and AP-1 was investigated by electrophoretic mobility shift assay. Protein expression was determined by Western blot. Cell proliferation was significantly inhibited by the combination of cetuximab and tectochrysin than treatment with cetuximab or tectochrysin alone (combination index: 0.572 and 0.533, respectively). Combination treatment of cells with cetuximab and tectochrysin significantly reduced the expressions of p-EGFR and COX-2 in both cell lines. Combination treatment also significantly inhibited activities of NF-kB and AP-1 compared to the single agent treatment. Our results indicate that combined therapy with lower concentration of cetuximab and tectochrysin could significantly enhance the cancer cell growth inhibitory effect through the inhibition of EGFR signaling.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cetuximab/farmacologia , Receptores ErbB/antagonistas & inibidores , Flavonoides/farmacologia , Alpinia/química , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Ciclo-Oxigenase 2/genética , Sinergismo Farmacológico , Flavonoides/administração & dosagem , Flavonoides/isolamento & purificação , Células HCT116 , Humanos
15.
Arch Toxicol ; 90(2): 463-77, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25417048

RESUMO

We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 µg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 µM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.


Assuntos
NF-kappa B/antagonistas & inibidores , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Venenos de Víboras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Biomed Res Int ; 2015: 397563, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26491668

RESUMO

The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.


Assuntos
Cetuximab/farmacologia , Cisplatino/farmacologia , Neoplasias do Colo , Receptores ErbB/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/agonistas , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sinergismo Farmacológico , Humanos
17.
Oncotarget ; 6(33): 35040-50, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26418900

RESUMO

This study was designed to investigate whether proton pump inhibitors (PPI, V-ATPase blocker) could increase the effect of cytotoxic agents in chemoresistant epithelial ovarian cancer (EOC). Expression of V-ATPase protein was evaluated in patients with EOC using immunohistochemistry, and patient survival was compared based on expression of V-ATPase mRNA from a TCGA data set. In vitro, EOC cell lines were treated with chemotherapeutic agents with or without V-ATPase siRNA or PPI (omeprazole) pretreatment. Cell survival and apoptosis was assessed using MTT assay and ELISA, respectively. In vivo experiments were performed to confirm the synergistic effect with omeprazole and paclitaxel on tumor growth in orthotopic and patient-derived xenograft (PDX) mouse models. Expression of V-ATPase protein in ovarian cancer tissues was observed in 44 patients (44/59, 74.6%). Higher expression of V-ATPase mRNA was associated with poorer overall survival in TCGA data. Inhibition of V-ATPase by siRNA or omeprazole significantly increased cytotoxicity or apoptosis to paclitaxel in chemoresistant (HeyA8-MDR, SKOV3-TR) and clear cell carcinoma cells (ES-2, RMG-1), but not in chemosensitive cells (HeyA8, SKOV3ip1). Moreover, the combination of omeprazole and paclitaxel significantly decreased the total tumor weight compared with paclitaxel alone in a chemoresistant EOC animal model and a PDX model of clear cell carcinoma. However, this finding was not observed in chemosensitive EOC animal models. These results show that omeprazole pretreatment can increase the effect of chemotherapeutic agents in chemoresistant EOC and clear cell carcinoma via reduction of the acidic tumor microenvironment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , Adulto , Animais , Western Blotting , Carcinoma Epitelial do Ovário , Resistencia a Medicamentos Antineoplásicos/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Epiteliais e Glandulares/mortalidade , Omeprazol/farmacologia , Neoplasias Ovarianas/mortalidade , Paclitaxel/farmacologia , RNA Interferente Pequeno , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Mol Cancer ; 14: 124, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26123287

RESUMO

BACKGROUND: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables. Epidemiologic studies showed that flavonoids also reduce the risk of colon cancer. Tectochrysin is one of the major flavonoids of Alpinia oxyphylla Miquel. However, the anti-cancer effects and the molecular mechanisms of tectochrysin in colon cancer cells have not yet been reported. We investigated whether tectochrysin could inhibit colon cancer cell growth at 1, 5, 10 µg/ml. In in vivo study, we injected a tectochrysin treatment dose of 5 mg/kg to each mouse. RESULTS: Tectochrysin suppressed the growth of SW480 and HCT116 human colon cancer cells. The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased. Tectochrysin treatment also inhibited activity of NF-κB. A docking model indicated that tectochrysin binds directly to the p50 unit. In in vivo, tumor weights and volumes in mice were reduced when treated with tectochrysin. Tectochrysin leads to apoptotic cell death in colon cancer cells through activation of death receptors expression via the inhibition of NF-κB. CONCLUSIONS: Tectochrysin can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Flavonoides/farmacologia , NF-kappa B/metabolismo , Receptores de Morte Celular/metabolismo , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Flavonoides/química , Células HCT116 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor fas/metabolismo
19.
Nanoscale Res Lett ; 10: 20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25852318

RESUMO

The effects of grain size and strain on the temperature-dependent thermal transport of antimony telluride (Sb2Te3) thin films, controlled using post-annealing temperatures of 200°C to 350°C, were investigated using the 3-omega method. The measured total thermal conductivities of 400-nm-thick thin films annealed at temperatures of 200°C, 250°C, 300°C, 320°C, and 350°C were determined to be 2.0 to 3.7 W/m · K in the 20 to 300 K temperature range. We found that the film grain size, rather than the strain, had the most prominent effect on the reduction of the total thermal conductivity. To confirm the effect of grain size on temperature-dependent thermal transport in the thin films, the experimental results were analyzed using a modified Callaway model approach.

20.
Obesity (Silver Spring) ; 23(3): 615-22, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25645248

RESUMO

OBJECTIVE: Chronic excessive food intake leads to energy imbalance, resulting in hepatic steatosis and inflammation. Interleukin-32 (IL-32) is known to be a pro-inflammatory cytokine associated with chronic inflammation and cancer. Therefore, the relationship between IL-32 and chronic excessive food intake-induced liver disease was investigated. METHODS: Male IL-32ß transgenic and wild-type mice were fed a high-fat diet (HFD) for 15 weeks. They were compared with wild-type mice on a standard chow diet. Daily food intake, body and liver weight, serum biochemistry, histopathological analysis of the liver, and hepatic immune response were determined. RESULTS: IL-32ß mice on HFD showed lower lipid accumulation, reduced infiltration of immune cells, and lower production of pro-inflammatory cytokines in the liver. The expression of the peroxisome proliferator-activated receptor γ (PPARγ) was downregulated and the adenosine 50-monophosphate (AMP)-activated protein kinase (AMPK) was activated in the liver of IL-32ß mice compared to wild-type mice. Furthermore, IL-32ß over-expression activated the AMPK pathway and IL-32ß downregulation inactivated the AMPK pathway in HepG2 cells under high-glucose conditions. CONCLUSIONS: These data suggest that IL-32ß modulates lipid accumulation through inhibition of PPARγ expression and AMPK activation.


Assuntos
Dieta Hiperlipídica , Fígado Gorduroso/genética , Interleucinas/fisiologia , Doenças Metabólicas/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Citocinas/metabolismo , Fígado Gorduroso/metabolismo , Células Hep G2 , Humanos , Inflamação/genética , Inflamação/metabolismo , Interleucinas/antagonistas & inibidores , Interleucinas/genética , Metabolismo dos Lipídeos/genética , Masculino , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Transgênicos , PPAR gama/metabolismo , RNA Interferente Pequeno/farmacologia
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