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1.
Lab Invest ; 104(1): 100285, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37949359

RESUMO

Cutaneous neurofibromas (cNFs) are characteristic of neurofibromatosis 1 (NF1), yet their immune microenvironment is incompletely known. A total of 61 cNFs from 10 patients with NF1 were immunolabeled for different types of T cells and macrophages, and the cell densities were correlated with clinical characteristics. Eight cNFs and their overlying skin were analyzed for T cell receptor CDR domain sequences, and mass spectrometry of 15 cNFs and the overlying skin was performed to study immune-related processes. Intratumoral T cells were detected in all cNFs. Tumors from individuals younger than the median age of the study participants (33 years), growing tumors, and tumors smaller than the data set median showed increased T cell density. Most samples displayed intratumoral or peritumoral aggregations of CD3-positive cells. T cell receptor sequencing demonstrated that the skin and cNFs host distinct T cell populations, whereas no dominant cNF-specific T cell clones were detected. Unique T cell clones were fewer in cNFs than in skin, and mass spectrometry suggested lower expression of proteins related to T cell-mediated immunity in cNFs than in skin. CD163-positive cells, suggestive of M2 macrophages, were abundant in cNFs. Human cNFs have substantial T cell and macrophage populations that may be tumor-specific.


Assuntos
Neurofibroma , Neurofibromatose 1 , Neoplasias Cutâneas , Humanos , Adulto , Neurofibromatose 1/patologia , Neurofibroma/metabolismo , Neurofibroma/patologia , Neoplasias Cutâneas/metabolismo , Receptores de Antígenos de Linfócitos T , Microambiente Tumoral
2.
ACS Appl Mater Interfaces ; 15(48): 56084-56094, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38058106

RESUMO

Currently, most carbon monoxide (CO) gas sensors work at high temperatures of over 150 °C. Developing CO gas sensors that operate at room temperature is challenging because of the sensitivity trade-offs. Here, we report an ultrasensitive CO gas sensor at room temperature using fluorine-graphdiyne (F-GDY) in which electrons are increased by light. The GDY films used as channels of field-effect transistors were prepared by using chemical vapor deposition and were characterized by using various spectroscopic techniques. With exposure to UV light, F-GDY showed a more efficient photodoping effect than hydrogen-graphdiyne (H-GDY), resulting in a larger negative shift in the charge neutral point (CNP) to form an n-type semiconductor and an increase in the Fermi level from -5.27 to -5.01 eV. Upon CO exposure, the negatively shifted CNP moved toward a positive shift, and the electrical current decreased, indicating electron transfer from photodoped GDYs to CO. Dynamic sensing experiments demonstrated that negatively charged F-GDY is remarkably sensitive to an electron-deficient CO gas, even with a low concentration of 200 parts per billion. This work provides a promising solution for enhancing the CO sensitivity at room temperature and expanding the application of GDYs in electronic devices.

3.
Adv Sci (Weinh) ; 10(25): e2300925, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37424035

RESUMO

Graphdiyne (GDY), a new 2D material, has recently proven excellent performance in photodetector applications due to its direct bandgap and high mobility. Different from the zero-gap of graphene, these preeminent properties made GDY emerge as a rising star for solving the bottleneck of graphene-based inefficient heterojunction. Herein, a highly effective graphdiyne/molybdenum (GDY/MoS2 ) type-II heterojunction in a charge separation is reported toward a high-performance photodetector. Characterized by robust electron repulsion of alkyne-rich skeleton, the GDY based junction facilitates the effective electron-hole pairs separation and transfer. This results in significant suppression of Auger recombination up to six times at the GDY/MoS2 interface compared with the pristine materials owing to an ultrafast hot hole transfer from MoS2 to GDY. GDY/MoS2 device demonstrates notable photovoltaic behavior with a short-circuit current of -1.3 × 10-5 A and a large open-circuit voltage of 0.23 V under visible irradiation. As a positive-charge-attracting magnet, under illumination, alkyne-rich framework induces positive photogating effect on the neighboring MoS2 , further enhancing photocurrent. Consequently, the device exhibits broadband detection (453-1064 nm) with a maximum responsivity of 78.5 A W-1 and a high speed of 50 µs. Results open up a new promising strategy using GDY toward effective junction for future optoelectronic applications.

4.
J Clin Immunol ; 43(2): 358-370, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36260239

RESUMO

Abnormally high γδ T cell numbers among individuals with atypical SCID have been reported but detailed immunophenotyping and functional characterization of these expanded γδ T cells are limited. We have previously reported atypical SCID phenotype caused by hypomorphic IL2RG (NM_000206.3) c.172C > T;p.(Pro58Ser) variant. Here, we have further investigated the index patient's abnormally large γδ T cell population in terms of function and phenotype by studying IL2RG cell surface expression, STAT tyrosine phosphorylation and blast formation in response to interleukin stimulation, immunophenotyping, TCRvγ sequencing, and target cell killing. In contrast to his âºß T cells, the patient's γδ T cells showed normal IL2RG cell surface expression and normal or enhanced IL2RG-mediated signaling. Vδ2 + population was proportionally increased with a preponderance of memory phenotypes and high overall tendency towards perforin expression. The patient's γδ T cells showed enhanced cytotoxicity towards A549 cancer cells. His TCRvγ repertoire was versatile but sequencing of IL2RG revealed a novel c.534C > A; p.(Phe178Leu) somatic missense variant restricted to γδ T cells. Over time this variant became predominant in γδ T cells, though initially present only in part of them. IL2RG-Pro58Ser/Phe178Leu variant showed higher cell surface expression compared to IL2RG-Pro58Ser variant in stable HEK293 cell lines, suggesting that somatic p.(Phe178Leu) variant may at least partially rescue the pathogenic effect of germline p.(Pro58Ser) variant. In conclusion, our report indicates that expansion of γδ T cells associated with atypical SCID needs further studying and cannot exclusively be deemed as a homeostatic response to low numbers of conventional T cells.


Assuntos
Linfócitos Intraepiteliais , Imunodeficiência Combinada Severa , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X , Humanos , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Linfócitos Intraepiteliais/patologia , Células HEK293 , Receptores de Antígenos de Linfócitos T gama-delta/genética , Subunidade gama Comum de Receptores de Interleucina/genética
5.
J Eur Acad Dermatol Venereol ; 35(1): 222-229, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32702138

RESUMO

BACKGROUND: Systemic effects of long-term narrowband ultraviolet B (NB-UVB) phototherapy have not been well studied in vitiligo patients. An 11-year nationwide population-based retrospective cohort study was conducted using the Korean National Health Insurance claims database (2007-2017). OBJECTIVES: To investigate the effects of long-term NB-UVB phototherapy on the risk of cardiovascular and cerebrovascular events in vitiligo patients. METHODS: This study included vitiligo patients with ≥100 phototherapy sessions (phototherapy group, n = 3229) and <3 phototherapy sessions (no phototherapy group, n = 9687), in which covariables with age, sex, insurance type and comorbidities such as diabetes, hypertension and hyperlipidemia were matched by 1 : 3 propensity score matching. The outcomes of interest were cardiovascular (ischaemic heart disease and myocardial infarction) and cerebrovascular events (cerebrovascular infraction and haemorrhage). Cox proportional hazards models were used to assess the associations between NB-UVB phototherapy and each event. RESULTS: The risk of cardiovascular or cerebrovascular events was significantly decreased in the phototherapy group compared with the no phototherapy group [hazard ratio (HR) 0.637, 95% confidence interval (CI) 0.523-0.776]. Subgroup analysis revealed that the risk of cardiovascular (HR: 0.682, 95% CI: 0.495-0.940) and cerebrovascular events (HR: 0.601, 95% CI: 0.470-0.769) were significantly lower in the phototherapy group than the no phototherapy group, respectively. CONCLUSIONS: Our findings suggest that long-term NB-UVB phototherapy could decrease the risk of cardiovascular and cerebrovascular events in patients with vitiligo.


Assuntos
Terapia Ultravioleta , Vitiligo , Humanos , Fototerapia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Terapia Ultravioleta/efeitos adversos , Vitiligo/radioterapia
6.
J Appl Microbiol ; 128(5): 1524-1531, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31883170

RESUMO

AIMS: As cell-adapted foot-and-mouth disease virus (FMDV) with H56R mutation in VP3 has reduced thermostability, this study aimed to investigate the effect of thermostabilizers on cell-adapted FMDV for vaccine production. METHODS AND RESULTS: We examined the effect of 3% sucrose, 10% (or 25%) glycerol or 10% FBS on cell-adapted FMDV O/SKR/JC/2014, containing H56R mutation in VP3, as vaccine seed virus at -80, 4, 25 or 37°C for 2, 4 or 7 days. The stabilizing effect of 3% sucrose on O/SKR/JC/2014 was observed at 25, 37°C, and after repeated freeze-thaw cycles. Additionally, we tested the effect of 3% sucrose on the growth of FMDV or cells and did not observe any decrease in either viral growth or cell viability. CONCLUSIONS: Our study showed the protective effect of 3% sucrose on FMDV infectivity at various temperatures; this virus stock in 3% sucrose could be used for infecting cells without the removal of sucrose. SIGNIFICANCE AND IMPACT OF THE STUDY: We suggest that 3% sucrose-containing medium could be beneficial for the stable storage and transport of cell-adapted FMDV.


Assuntos
Vírus da Febre Aftosa/crescimento & desenvolvimento , Sacarose/análise , Excipientes de Vacinas/análise , Vacinas Virais/química , Animais , Proteínas do Capsídeo/genética , Sobrevivência Celular/efeitos dos fármacos , Febre Aftosa/virologia , Vírus da Febre Aftosa/efeitos dos fármacos , Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/imunologia , Mutação , Sacarose/farmacologia , Temperatura , Excipientes de Vacinas/farmacologia , Potência de Vacina
7.
Biochemistry (Mosc) ; 84(12): 1537-1546, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31870258

RESUMO

The Notch1 signaling pathway plays a crucial role in determining cell fate, including cell growth and differentiation. In this study, we demonstrated that the antagonistic action of RTK (receptor tyrosine kinase) signaling pathway on the Notch1 signaling pathway is mediated via Ras-PI3K-Akt1. The PI3K-Akt1 signaling pathway was shown to inhibit Notch1 signaling via phosphorylation of RBP-Jk. We observed not only reduced association between Notch1 and RBP-Jk, but also suppression of the Notch1 transcriptional activity. Our results demonstrated that Akt1 functions as a natural inhibitor of the Notch1 signaling pathway via phosphorylation of RBP-Jk.


Assuntos
Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Animais , Camundongos , Células NIH 3T3 , Fosforilação , Transcrição Gênica
8.
Allergy ; 73(9): 1833-1841, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29517808

RESUMO

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.


Assuntos
Anafilaxia/epidemiologia , Anafilaxia/etiologia , Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anafilaxia/diagnóstico , Anafilaxia/mortalidade , Antibacterianos/administração & dosagem , Antibacterianos/química , Cefalosporinas/administração & dosagem , Cefalosporinas/química , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Incidência , Testes Intradérmicos/métodos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Estudos Retrospectivos
9.
Br J Oral Maxillofac Surg ; 55(9): 971-973, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29037585

RESUMO

To the best of our knowledge, this is the first report to discuss the possible mechanisms of an iatrogenic fracture during operation on an original mandibular fracture in a patient with osteogenesis imperfecta.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Mandibulares/etiologia , Fraturas Mandibulares/cirurgia , Osteogênese Imperfeita/cirurgia , Adulto , Humanos , Doença Iatrogênica , Masculino , Má Oclusão Classe III de Angle/diagnóstico por imagem , Fraturas Mandibulares/diagnóstico por imagem , Osteogênese Imperfeita/diagnóstico por imagem , Radiografia Panorâmica
10.
Mol Cell Proteomics ; 15(9): 3030-44, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27432908

RESUMO

Protein tyrosine phosphorylation, which plays a vital role in a variety of human cellular processes, is coordinated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Genomic studies provide compelling evidence that PTPs are frequently mutated in various human cancers, suggesting that they have important roles in tumor suppression. However, the cellular functions and regulatory machineries of most PTPs are still largely unknown. To gain a comprehensive understanding of the protein-protein interaction network of the human PTP family, we performed a global proteomic study. Using a Minkowski distance-based unified scoring environment (MUSE) for the data analysis, we identified 940 high confidence candidate-interacting proteins that comprise the interaction landscape of the human PTP family. Through a gene ontology analysis and functional validations, we connected the PTP family with several key signaling pathways or cellular functions whose associations were previously unclear, such as the RAS-RAF-MEK pathway, the Hippo-YAP pathway, and cytokinesis. Our study provides the first glimpse of a protein interaction network for the human PTP family, linking it to a number of crucial signaling events, and generating a useful resource for future studies of PTPs.


Assuntos
Mapas de Interação de Proteínas , Proteínas Tirosina Fosfatases/metabolismo , Proteômica/métodos , Ontologia Genética , Redes Reguladoras de Genes , Células HEK293 , Células HeLa , Humanos , Família Multigênica , Especificidade por Substrato
11.
Int J Oral Maxillofac Surg ; 45(7): 878-83, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26987694

RESUMO

The purpose of this study was to determine a practical and cost-effective treatment method for fixing mandibular angle fractures using miniplates. Patients were divided into three groups for comparison, based on the intraoperative plates and maxillomandibular fixation (MMF) used: group A, single miniplate fixation with MMF (n=37); group B, double miniplate fixation with MMF (n=59); group C, double miniplate fixation without MMF (n=38). Details of the characteristics of the fractures and the treatments and outcomes were collected retrospectively and analyzed statistically. This study was based on 134 cases of isolated mandibular angle fracture. Of the surgically treated patients, 78.4% (n=105) were completely free of complications. A detailed complication correlation matrix is given in the text. Besides screw loosening and malocclusion, no statistically significant difference was observed between the groups. The results of this study suggest that treatment with single miniplate fixation and MMF has a low incidence rate of complications, and this method of treatment is considered to be simple.


Assuntos
Placas Ósseas , Técnicas de Fixação da Arcada Osseodentária , Fraturas Mandibulares/cirurgia , Adolescente , Adulto , Criança , Análise Custo-Benefício , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Mandíbula , Fraturas Mandibulares/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto Jovem
12.
Oncogene ; 35(35): 4569-79, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-26898760

RESUMO

The role of poly (ADP-ribose) polymerase 1 (PARP1) in cancer has been extensively studied in the context of DNA repair, leading to clinical trials of PARP1 inhibitors in cancers defective in homologous recombination. However, the DNA repair-independent roles of PARP1 in carcinogenesis and metastasis, particularly in lung cancer metastasis, remain largely uncharacterized. Here, we report that PARP1 promotes lung adenocarcinoma relapse to the brain and bones by regulating several steps of the metastatic process in a DNA repair-independent manner. We find that PARP1 expression is associated with overall and distant metastasis-free survival in lung adenocarcinoma patients. Consistent with this, genetic knockdown and pharmacological inhibition of PARP1 significantly attenuated the metastatic potential of lung adenocarcinoma cells. Further investigation revealed that PARP1 potentiates lung adenocarcinoma metastasis by promoting invasion, anoikis resistance, extravasation and self-renewal of lung adenocarcinoma cells and also by modifying the brain microenvironment. Finally, we identified S100A4 and CLDN7 as novel transcriptional targets and clinically relevant effectors of PARP1. Collectively, our study not only revealed previously unknown functions of PARP1 in lung adenocarcinoma metastasis but also delineated the molecular mechanisms underlying the pro-metastatic function of PARP1. Furthermore, these findings provide a foundation for the potential use of PARP1 inhibitors as a new treatment option for lung adenocarcinoma patients with elevated PARP1 expression.


Assuntos
Adenocarcinoma/genética , Claudinas/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Carcinogênese/genética , Linhagem Celular Tumoral , Reparo do DNA/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Recombinação Homóloga , Humanos , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Proteína A4 de Ligação a Cálcio da Família S100/genética
13.
Int J Tuberc Lung Dis ; 20(1): 115-20, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26688537

RESUMO

BACKGROUND: The performance of Xpert(®) MTB/RIF assay, an automated nucleic acid amplification test (NAAT) that was developed for the detection of tuberculosis (TB), has been evaluated in various clinical settings. However, few studies have compared Xpert with other NAATs, especially its performance using lower respiratory tract specimens (LRTS). OBJECTIVE: To compare the practical diagnostic performance of the Xpert assay with that of the AdvanSure™ TB/NTM RT-PCR kit in the detection of pulmonary TB (PTB), using LRTS obtained through bronchoscopy. RESULTS: Of 249 patients included, 105 had culture-confirmed PTB. Using culture as reference, the overall sensitivity of Xpert and AdvanSure was respectively 92.4% and 83.8%. When acid-fast bacilli smear results were taken into consideration, the sensitivity of Xpert for smear-positive and smear-negative LRTS was respectively 100% and 88.9%, while that of the AdvanSure was 100% and 76.4%. Xpert showed better results than AdvanSure in terms of sensitivity in smear-negative LRTS (P = 0.012), but no difference in smear-positive LRTS. CONCLUSIONS: Xpert may be advantageous in the detection of PTB using LRTS, particularly in low microbiological burden settings.


Assuntos
Técnicas de Diagnóstico Molecular/normas , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Broncoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , República da Coreia , Estudos Retrospectivos
14.
Nutr Diabetes ; 5: e179, 2015 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-26302066

RESUMO

BACKGROUND/OBJECTIVES: Increased adipose tissue mass closely associates with the development of insulin resistance and type 2 diabetes mellitus. Previously, we reported that CREB3L4 expressed in adipose tissue negatively regulates adipogenesis, and Creb3l4 knockout mice fed a high-fat diet for 16 weeks showed fat cell hyperplasia, with improved glucose tolerance and insulin sensitivity. These mice did not show significant weight gain and fat mass. Because fat diet or aging is known to be associated with the development of obesity, we examined the effects of Creb3l4 gene subjected to low-fat diet (LFD) or aging process on body composition and obesity risk. SUBJECTS/METHODS: We fed Creb3l4 knockout mice a low-fat diet for 16 weeks (LFD group) or chow diet for over 1 year (aged group) and observed various metabolic parameters in the LFD-fed and aged Creb3l4 knockout mice. RESULTS: LFD-fed and aged Creb3l4 knockout mice showed significant weight gain and adiposity, impaired glucose tolerance and decreased insulin sensitivity, compared with wild-type mice. CONCLUSIONS: Creb3l4 has a critical role in metabolic phenotypes and a better understanding of its function may provide improved insight into the etiology of diabetes and other metabolic disorders.

15.
Int J Tuberc Lung Dis ; 19(5): 589-95, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25868029

RESUMO

OBJECTIVE: To evaluate changes in lung function in individuals before and after treatment for pulmonary tuberculosis (PTB) in relation to extent of disease. DESIGN: Using a retrospective cohort design, changes in and predictors of lung function were evaluated. RESULTS: A total of 41 patients were included in the final analysis. The median decline in annualised forced expiratory volume in 1 sec (FEV1) was 180.0 ml/year (95%CI 118.9-356.1) in advanced PTB and 94.7 ml/year (95%CI 33.4-147.3) in localised PTB (ΔFEV1% predicted/year 9.4%, 95%CI 4.4-14.0 vs. 3.8%, 95%CI 1.8-6.2). The median decline in annualised forced vital capacity (FVC) was 309.6 ml/year (95%CI 137.0-359.0) in advanced PTB and 101.1 ml/year (95%CI 30.3-219.6) in localised PTB (ΔFVC % predicted/year 7.3%, 95%CI 5.3-12.3 vs. 2.9%, 95%CI 0.9-6.5). CONCLUSIONS: As the sample size of our study was small, the conclusions could be biased. Nevertheless, our findings show that PTB causes a significant decline in lung function even in localised PTB, whereas advanced PTB was associated with excessive or even higher decline. This study suggests that early diagnosis and treatment of PTB is needed to preserve lung function.


Assuntos
Progressão da Doença , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/fisiopatologia , Capacidade Vital/fisiologia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Valores de Referência , República da Coreia , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos
16.
Cell Death Dis ; 5: e1527, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25412305

RESUMO

Understanding the molecular networks that regulate adipogenesis is crucial for combating obesity. However, the identity and molecular actions of negative regulators that regulate the early development of adipocytes remain poorly understood. In this study, we investigated the role of CREB3L4, a member of the CREB3-like family, in the regulation of adiposity. Constitutive overexpression of CREB3L4 resulted in the inhibition of adipocyte differentiation, whereas knockdown of Creb3l4 expression caused differentiation of preadipocytes into mature adipocytes, bypassing the mitotic clonal expansion step. In 3T3-L1 preadipocytes, Creb3l4 knockdown resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ2) and CCAAT/enhancer binding protein (C/EBPα), either by increasing the protein stability of C/EBPß or by decreasing the expression of GATA3, a negative regulator of PPARγ2 expression. Consequently, increased PPARγ2 and C/EBPα levels induced adipocyte differentiation, even in the presence of minimal hormonal inducer. Thus, it can be speculated that CREB3L4 has a role as gatekeeper, inhibiting adipogenesis in 3T3-L1 preadipocytes. Moreover, adipocytes of Creb3l4-knockout mice showed hyperplasia caused by increased adipogenesis, and exhibited improved glucose tolerance and insulin sensitivity, as compared with littermate wild-type mice. These results raise the possibility that Creb3l4 could be a useful therapeutic target in the fight against obesity and metabolic syndrome.


Assuntos
Adipócitos/metabolismo , Adipogenia/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Obesidade/genética , PPAR gama/genética , Células 3T3-L1 , Adipócitos/patologia , Adiposidade/genética , Animais , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Resistência à Insulina , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Transdução de Sinais
17.
J Obstet Gynaecol ; 33(2): 160-2, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23445139

RESUMO

The safety of domperidone in pregnancy remains unknown. Therefore, the study aimed to prospectively evaluate the fetal outcomes of women who were taking domperidone during pregnancy. In a prospective cohort study design, 120 1st- trimester pregnant women who were taking domperidone for controlling gastrointestinal tract symptoms and 212 age-matched pregnant women not exposed to any potential teratogenic agent, were followed-up until delivery. In the case group, domperidone was indicated for control of functional gastrointestinal disorders in 59.2%, the maximum dose was 30 mg/day and exposure occurred between 2(+4) and 20 weeks' gestation. Fetal outcomes including gestational age at birth, birth weight and length, head circumference at birth, and 1- and 5-min Apgar score were similar in the two study groups. There were three babies born with malformations in each group (OR = 0.6; 95% CI 0.1, 2.8). In conclusion, domperidone does not appear to be a major human teratogen. However, our findings require further confirmation in larger studies.


Assuntos
Antieméticos/efeitos adversos , Peso ao Nascer/efeitos dos fármacos , Domperidona/efeitos adversos , Desenvolvimento Fetal/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos
18.
Eur J Clin Nutr ; 67(2): 196-201, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23385969

RESUMO

BACKGROUND/OBJECTIVES: Gestational diabetes mellitus (GDM) risk factors are well established for Caucasians, but not for Asians. We hypothesized that nutrient intakes, plasma adipokines and/or gestational hormones might be linked to GDM development among pregnant Korean women. This study sought to identify new risk factors for GDM and adverse pregnancy outcomes according to body weight at prepregnancy. SUBJECTS/METHODS: All subjects were pregnant women visiting the Cheil General Hospital and Women's Healthcare Center between June 2006 and March 2009. Non-GDM (n=531) and GDM (n=215) participants were divided into normal-weight and overweight groups according to prepregnancy body mass index (BMI) above or below 23 kg/m(2) at 24-28th week of gestation. At that time, glucose tolerance, insulin resistance as homeostatic model assessment for insulin resistance, insulin secretory capacity as homeostatic model assessment for ß-cell function, anthropometric measurement, nutrient intakes, and plasma levels of adipokines and gestational hormones were determined. RESULTS: GDM women gained more weight in early pregnancy than non-GDM among normal-weight women. GDM was mainly associated with increased insulin resistance in overweight women and decreased insulin secretory capacity in normal-weight women. Plasma visfatin and adiponectin were lower and progesterone levels higher in GDM than non-GDM independent of BMI while plasma resistin levels were higher in non-GDM, but not GDM, overweight women. Energy and saturated fat intakes were higher in GDM independent of body weight, whereas taurine intakes were lower in GDM than non-GDM only in normal-weight women. CONCLUSIONS: Low visfatin and adiponectin and high progesterone levels in the circulation and high energy and saturated fat intakes were common risk factors for GDM and pregnancy outcome such as large for gestational age. Daily reference intakes for energy and fat during pregnancy need to be re-evaluated according to prepregnancy BMI.


Assuntos
Adiponectina/sangue , Índice de Massa Corporal , Diabetes Gestacional/etiologia , Gorduras na Dieta/efeitos adversos , Ingestão de Energia , Ácidos Graxos/efeitos adversos , Nicotinamida Fosforribosiltransferase/sangue , Diabetes Gestacional/sangue , Dieta/efeitos adversos , Feminino , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Sobrepeso , Gravidez , Progesterona/sangue , Valores de Referência , Fatores de Risco , Taurina/farmacologia , Aumento de Peso
19.
Endoscopy ; 45(2): 133-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23364841

RESUMO

Although endoscopic submucosal dissection (ESD) is increasingly utilized to treat early neoplasms of the gastrointestinal tract, its use for duodenal neoplasms is limited by the thin wall and narrow lumen of the duodenum. We have reviewed cases where ESD was used to treat sessile, nonampullary duodenal neoplasms. To do this, we retrospectively reviewed the medical records of patients treated with ESD for adenomas of the duodenum from January 2001 to December 2010, assessing the curative outcomes and complication rates. A total of 14 cases were reviewed. Mean patient age was 56.4 years. The mean size of tumors and mean size of the specimens were 17.1 mm and 26.4 mm, respectively. The en bloc resection rate with ESD was 78.6%, and the complete (R0) resection rate was 85.7%. No patient in the study experienced major bleeding. However, second-look endoscopy revealed minor bleeding requiring endoscopic homeostasis in one case (7.1%). Perforations were observed in five cases (35.7%). Two of the five patients with perforation underwent surgery. The ESD methods yielded acceptable curative resection rates for duodenal adenomas, although ESD was associated with a higher rate of perforation. Therefore, duodenal ESD should be performed with care and only in selected patients to avoid serious complications.


Assuntos
Adenoma/cirurgia , Neoplasias Duodenais/cirurgia , Duodenoscopia , Duodeno , Mucosa Intestinal/cirurgia , Perfuração Intestinal/etiologia , Adenoma/patologia , Dissecação/efeitos adversos , Neoplasias Duodenais/patologia , Duodenoscopia/efeitos adversos , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos
20.
Br J Radiol ; 86(1024): 20120209, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23440166

RESUMO

OBJECTIVE: To describe CT findings of non-tuberculous mycobacteria (NTM) pulmonary infection in non-AIDS immunocompromised patients (ICPs) and to compare these findings with those in immunocompetent patients. METHODS: From July 2000 to August 2007, 369 patients (mean age 58.3 years; 169 males and 200 females) with pulmonary NTM infection were retrospectively reviewed. Of these 369 patients, 24 ICPs (mean age 64.8 years; 15 males and 9 females) were identified. 16 patients had diabetes mellitus, and 6 patients had received long-term steroid therapy. One had received solid organ transplantation and one had received high-dose chemotherapy for haematological disease. 24 age- and sex-matched immunocompetent patients (mean age 64.6 years; 15 males and 9 females) were selected as the control group from the same registry. CT images were reviewed in consensus by three chest radiologists, who were blinded to immune status. Each lung lobe was evaluated in terms of extent of the lesion, bronchiectasis, parenchymal opacity and the presence of ancillary findings. results: A total of 287 lobes were evaluated in ICPs and the control group. The ICPs showed a higher prevalence of ill-defined nodules, with cavities and large opacity >2 cm with/without cavity (p=0.03, 0.04 and 0.02, respectively). Regardless of the immune status, the most common CT findings were bronchiectasis and ill-defined nodules without cavity. CONCLUSION: The most common CT findings of pulmonary NTM infection in ICPs were bronchiectasis and ill-defined nodules, similar to those in the control group. Ill-defined nodules with cavity and large opacity >2 cm with/without cavity were more frequently found in ICPs. ADVANCES IN KNOWLEDGE: In patients affected by NTM infection, large opacities and cavitation in pulmonary nodules are more frequent in ICPs than in immunocompetent patients.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Infecções por Mycobacterium não Tuberculosas/imunologia , Pneumonia Bacteriana/diagnóstico por imagem , Pneumonia Bacteriana/imunologia , Síndrome de Imunodeficiência Adquirida/diagnóstico por imagem , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Pneumonia Bacteriana/epidemiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
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