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1.
Korean J Physiol Pharmacol ; 27(4): 407-416, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37386838

RESUMO

The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment.

2.
Circulation ; 143(19): 1912-1925, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33715387

RESUMO

BACKGROUND: Although the clinical importance of heart failure with preserved ejection fraction has been extensively explored, most therapeutic regimens, including nitric oxide (NO) donors, lack therapeutic benefit. Although the clinical characteristics of heart failure with preserved ejection fraction are somewhat heterogeneous, diastolic dysfunction (DD) is one of the most important features. Here we report that neuronal NO synthase (nNOS) induces DD by S-nitrosylation of HDAC2 (histone deacetylase 2). METHODS: Two animal models of DD-SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) and mild transverse aortic constriction mice-as well as human heart samples from patients with left ventricular hypertrophy were used. Genetically modified mice that were either nNOS-ablated or HDAC2 S-nitrosylation-resistant were also challenged. N(ω)-propyl-L-arginine, an nNOS selective inhibitor, and dimethyl fumarate, an NRF2 (nuclear factor erythroid 2-related factor 2) inducer, were used. Molecular events were further checked in human left ventricle specimens. RESULTS: SAUNA or mild transverse aortic constriction stress impaired diastolic function and exercise tolerance without overt systolic failure. Among the posttranslational modifications tested, S-nitrosylation was most dramatically increased in both models. Utilizing heart samples from both mice and humans, we observed increases in nNOS expression and NO production. N(ω)-propyl-L-arginine alleviated the development of DD in vivo. Similarly, nNOS knockout mice were resistant to SAUNA stress. nNOS-induced S-nitrosylation of HDAC2 was relayed by transnitrosylation of GAPDH. HDAC2 S-nitrosylation was confirmed in both DD mouse and human left ventricular hypertrophy. S-nitrosylation of HDAC2 took place at C262 and C274. When DD was induced, HDAC2 S-nitrosylation was detected in wild-type mouse, but not in HDAC2 knock-in mouse heart that expressed HDAC2 C262A/C274A. In addition, HDAC2 C262A/C274A mice maintained normal diastolic function under DD stimuli. Gene delivery with adenovirus-associated virus 9 (AAV9)-NRF2, a putative denitrosylase of HDAC2, or pharmacological intervention by dimethyl fumarate successfully induced HDAC2 denitrosylation and mitigated DD in vivo. CONCLUSIONS: Our observations are the first to demonstrate a new mechanism underlying DD pathophysiology. Our results provide theoretical and experimental evidence to explain the ineffectiveness of conventional NO enhancement trials for improving DD with heart failure symptoms. More important, our results suggest that reduction of NO or denitrosylation of HDAC2 may provide a new therapeutic platform for the treatment of refractory heart failure with preserved ejection fraction.


Assuntos
Sopros Cardíacos/fisiopatologia , Histona Desacetilase 2/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Camundongos
3.
Sensors (Basel) ; 22(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36081016

RESUMO

Several pathogens that spread through the air are highly contagious, and related infectious diseases are more easily transmitted through airborne transmission under indoor conditions, as observed during the COVID-19 pandemic. Indoor air contaminated by microorganisms, including viruses, bacteria, and fungi, or by derived pathogenic substances, can endanger human health. Thus, identifying and analyzing the potential pathogens residing in the air are crucial to preventing disease and maintaining indoor air quality. Here, we applied deep learning technology to analyze and predict the toxicity of bacteria in indoor air. We trained the ProtBert model on toxic bacterial and virulence factor proteins and applied them to predict the potential toxicity of some bacterial species by analyzing their protein sequences. The results reflect the results of the in vitro analysis of their toxicity in human cells. The in silico-based simulation and the obtained results demonstrated that it is plausible to find possible toxic sequences in unknown protein sequences.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Microbiologia do Ar , Poluição do Ar em Ambientes Fechados/análise , Bactérias , Fungos , Humanos , Pandemias , Reprodutibilidade dos Testes
4.
J Epidemiol ; 31(12): 593-600, 2021 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-32863371

RESUMO

BACKGROUND: The incidence and prevalence of endometriosis remain unclear due to diagnostic difficulties. Especially, there has been little information regarding the population-based epidemiology of endometriosis. The purpose of this study is to estimate the prevalence and incidence of endometriosis in Korea based on the health insurance claims data. METHODS: This study is a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort, which correspond to approximately 1 million Korean populations from 2002 to 2013. Patients aged 15-54 years were selected, and the prevalence and incidence of endometriosis were estimated by time and age groups. RESULTS: The age-adjusted prevalence rate of endometriosis also increased from 2.12 per 1,000 persons (95% confidence interval [CI], 2.01-2.24) in 2002 to 3.56 per 1,000 persons (95% CI, 3.40-3.71) in 2013. The average adjusted incidence showed no statistically significant increase. However, the age-specific incidence of the 15-19 and 20-24 years age groups increased significantly from 0.24 and 1.29 per 1,000 persons in 2003 to 2.73 and 2.71 per 1,000 persons in 2013 (R2 = 0.93 and 0.77, P < 0.001), while the incidence rate of the age group 40-44 and 45-49 years decreased from 2.36 and 1.72 per 1,000 persons in 2003 to 0.81 and 0.27 per 1,000 persons in 2013 (R2 = 0.83 and 0.89, P < 0.001). CONCLUSION: The prevalence and incidence of endometriosis in Korean women were lower than that of previous reports in high-risk population studies. Furthermore, we found a significant increase in the diagnosis of endometriosis in younger age groups.


Assuntos
Endometriose , Estudos de Coortes , Endometriose/epidemiologia , Feminino , Humanos , Incidência , Programas Nacionais de Saúde , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos
5.
Biomed Chromatogr ; 35(3): e5007, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33067857

RESUMO

An analytical method was developed for the quantification of spinosad (sum of spinosyns A and D) in five animal-derived products (chicken breast, pork, beef, egg, and milk) using LC-MS/MS. The sample was extracted using acetonitrile/1% acetic acid and a combination of magnesium sulfate and sodium acetate salts. The sample was purified using multiwalled carbon nanotubes as sorbent via a dispersive-solid-phase extraction procedure. Matrix-matched calibration (seven-point) provided good linearity with coefficient of determination (R2 ) ≥0.99 for each product. The limits of detection and quantification (LOQs) ranged between 0.0003-0.03 and 0.001-0.1 mg/kg, respectively. Method validation was carried out after spiking the target standard to blank matrices at the concentration levels of LOQ, 2 × LOQ, and 10 × LOQ with three replicates for each. The average recoveries were between 74 and 104%, with relative standard deviations ≤9.68, which were within the acceptable range designated by the international organizations. The developed method was successfully applied for monitoring market samples collected throughout the Korean Peninsula, and none of the samples tested positive for the target analytes. It has therefore been shown that dehydration and acidification were effective to extract spinosad from animal-derived products.


Assuntos
Cromatografia Líquida/métodos , Macrolídeos/análise , Nanotubos de Carbono/química , Resíduos de Praguicidas/análise , Animais , Limite de Detecção , Modelos Lineares , Macrolídeos/química , Macrolídeos/isolamento & purificação , Carne/análise , Leite/química , Resíduos de Praguicidas/química , Resíduos de Praguicidas/isolamento & purificação , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em Tandem/métodos
6.
Medicina (Kaunas) ; 57(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201357

RESUMO

Background and Objectives: Bromelain is a mixture of protease obtained from pineapple fruits or stems. Even though the biological mechanism of action of bromelain has not been completely understood, it is well known that bromelain possesses anticancer, anti-inflammatory and immunomodulatory effects. This study investigated the anti-inflammatory effects of bromelain on lipopolysaccharide (LPS)-induced human dental pulp cells (hDPCs). Materials and Methods: Cell viability after bromelain treatment was measured using WST-1 assay. We exposed hDPCs to 5 µg/mL of LPS with 2.5 or 5 µg/mL of bromelain. We performed reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay to detect interleukin-1ß, interleukin-6, and interleukin-8 levels. Western blots were used to detect intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) levels. Immunofluorescence staining and Western blots were used to determine bromelain's anti-inflammatory mechanism. We also performed alkaline phosphatase and Alizarin red staining to verify mineralization nodule formation. Results: Bromelain at 2.5, 5, 10, or 20 µg/mL did not affect the viability of hDPCs significantly. LPS increased interleukin-1ß, interleukin-6, interleukin-8, ICAM-1 and VCAM-1 expression in hDPCs. Bromelain significantly decreased interleukin-1ß, interleukin-6, interleukin-8, ICAM-1, and VCAM-1 levels in hDPCs, which were stimulated by LPS. Bromelain treatment significantly reduced p65 phosphorylation in the cytoplasm and the nucleus. It also significantly decreased phosphorylation levels of extracellular signal-related kinases (ERK) and p38 mitogen-activated protein kinases (p38). Bromelain also promoted ALP activity and mineralized nodule formation. Conclusions: Bromelain inhibits the expression of inflammatory cytokines in LPS-stimulated hDPCs. The inhibitory effect of bromelain on inflammatory mediators is related to decreased NF-κB and the MAPK pathway. Therefore, bromelain might have the potential to be used for regenerative endodontics, including vital pulp therapy.


Assuntos
Bromelaínas , Lipopolissacarídeos , Anti-Inflamatórios/farmacologia , Bromelaínas/farmacologia , Células Cultivadas , Polpa Dentária , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico
7.
BMC Health Serv Res ; 20(1): 166, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131818

RESUMO

BACKGROUND: The look-back period is needed to define baseline population for estimating incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. The purpose of this study is to evaluate the impact of the various length of look-back period on the observed incidences of uterine leiomyoma, endometriosis and adenomyosis, and to estimate true incidences considering the misclassification errors in the longitudinal administrative data in Korea. METHODS: A total of 319,608 women between 15 to 54 years of age in 2002 were selected from Korea National Health Insurance Services (KNHIS) cohort database. In order to minimize misclassification bias incurred when applying various length of look-back period, we used 11 years of claim data to estimate the incidence by equally setting the look-back period to 11 years for each year using prediction model. The association between the year of diagnosis and the number of prevalent cases with the misclassification rates by each look-back period was investigated. Based on the findings, prediction models on the proportion of misclassified incident cases were developed using multiple linear regression. RESULTS: The proportion of misclassified incident cases of uterine leiomyoma, endometriosis and adenomyosis were 32.8, 10.4 and 13.6% respectively for the one-year look-back period in 2003. These numbers decreased to 6.3% in uterine leiomyoma and - 0.8% in both endometriosis and adenomyosis using all available look-back periods (11 years) in 2013. CONCLUSION: This study demonstrates approaches for estimating incidences considering the different proportion of misclassified cases for various length of look-back period. Although the prediction model used for estimation showed strong R-squared values, follow-up studies are required for validation of the study results.


Assuntos
Endometriose/epidemiologia , Leiomioma/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto Jovem
8.
BMC Oral Health ; 20(1): 101, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276610

RESUMO

BACKGROUND: Parathyroid hormone-related protein (PTHrP) plays an important role in many physiological processes, including bone regeneration. The function of PTHrP is similar to PTH. It promotes osteogenic differentiation in MC3T3-E1 cells. The aim of this study was to investigate whether PTHrP might have odontogenic differentiation ability in human dental pulp cells (hDPCs). METHODS: The viability of hDPCs after stimulation with PTHrP was measured. Real-time polymerase chain reaction and Western blot analysis were performed to evaluate the expression levels of odontogenic markers and activation of protein kinase B (PKB/AKT), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). To evaluate mineralized nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. RESULTS: PTHrP promoted odontogenic differentiation as evidenced by the formation of mineralized nodules, the induction of ALP activity, and the upregulation of odontogenic markers (dentin sialophosphoprotein and dentin matrix protein-1). The phosphorylation of AKT, ERK, JNK, and p38 was increased by PTHrP. However, an AKT inhibitor (LY294002), an ERK inhibitor (U0126), a JNK inhibitor (SP600125), and a p38 inhibitor (SB203580) inhibited the increase of mineralization induced by PTHrP. CONCLUSION: The present study revealed that PTHrP could promote odontogenic differentiation and mineralization through activating the AKT, ERK, JNK, and p38 signaling pathways. These results provide novel insights into the odontogenic action of PTHrP.


Assuntos
Diferenciação Celular , Polpa Dentária/efeitos dos fármacos , Odontogênese/efeitos dos fármacos , Proteína Relacionada ao Hormônio Paratireóideo/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Polpa Dentária/citologia , Humanos , Osteogênese
9.
Biomed Chromatogr ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28731579

RESUMO

Residue analysis of dimethomorph in Swiss chard cultivated at two different locations under greenhouse conditions was conducted using high-performance liquid chromatography-ultraviolet detection and confirmed by tandem mass spectrometry. The randomly collected samples (over 14 days) were extracted with acetonitrile and purified using a Florisil solid-phase extraction cartridge. Linearity over a concentration range of 0.05-50.0 mg/L had an excellent coefficient of determination of 0.9996. Recovery rate ranged from 82.98 to 95.43% with relative standard deviations ≤5.12% and limits of detection and quantification of 0.003 and 0.01 mg/kg, respectively. The initial deposits [day 0 (2 h post-application)] were considerably lower (7.57 and 8.55 mg/kg for sites 1 and 2, respectively) than the maximum residue limit (30 mg/kg) set by the Korean Ministry of Food and Drug Safety. The dissipation half-life was approximately the same, being 5.0 and 5.1 days for sites 1 and 2, respectively. Risk assessment estimated as acceptable daily intake revealed a value of 0.084 or 0.094% (day 0) and 0.014% (10 days post-application), for sites 1 and 2, respectively. The values indicated that dimethomorph can be safely used on Swiss chard, with no hazardous effects expected for Korean consumers.


Assuntos
Beta vulgaris/química , Morfolinas/análise , Resíduos de Praguicidas/análise , Cromatografia Líquida de Alta Pressão/métodos , Inocuidade dos Alimentos , Limite de Detecção , Modelos Lineares , Morfolinas/química , Resíduos de Praguicidas/química , Reprodutibilidade dos Testes , República da Coreia , Medição de Risco , Espectrometria de Massas em Tandem/métodos
10.
Anal Biochem ; 530: 31-39, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28465033

RESUMO

Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z < 500). Reproducibility of inter-spot and intra-spot analyses of amino acids was less than 10%. Methanol extraction was adopted for simple and rapid sample preparation of serum before mass spectrometric analysis showing 13.3 to 45% of extraction efficiency. Calibration curves for diagnosis of neonatal metabolic disorders were obtained by analyzing methanol-extracted serum spiked with target amino acids using MALDI-ToF MS. They showed good linearity (R2 > 0.98) and the LODs were ranging from 9.0 to 22.9 µg/mL. Effect of proteins in serum was estimated by comparing MALDI-ToF mass spectra of amino acids-spiked serum before and after the methanol extraction. Interference of other amino acids on analysis of target analyte was determined to be insignificant. From these results, MALDI-ToF MS based on parylene-matrix chip could be applicable to medical diagnosis of neonatal metabolic disorders.


Assuntos
Aminoácidos/sangue , Triagem Neonatal/métodos , Polímeros/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Xilenos/química , Aminoácidos/química , Humanos , Recém-Nascido , Limite de Detecção , Reprodutibilidade dos Testes
11.
Biomed Chromatogr ; 31(5)2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27696449

RESUMO

This study was undertaken to quantify the residue levels and propose the dissipation kinetics of thiacloprid formulated as suspension concentrate in field-incurred Asian pears grown under two different open-field conditions. Samples were extracted with 20% distilled water in acetonitrile; partitioned with brine water and dichloromethane; and purified with a Florisil solid phase extraction cartridge. The analyte was identified with an LC ultraviolet detector, and field-incurred samples were confirmed using LC-MS/MS. The calibration curve was linear over the range 0.05-5.0 mg/L with a satisfactory coefficient of determination (R2 = 0.9994). The limits of detection and limits of quantification (LOQ) were 0.003 and 0.01 mg/kg, respectively. The recovery rate fortified to blank samples at LOQ, 10× LOQ, and the maximum residue limit (MRL) were between 73.7 and 86.2% with relative standard deviation ≤9.0%. The residual concentrations at both sites were considerably lower than the MRL (0.7 mg/kg) set by the Korean Ministry of Food Drug Safety, with biological half-lives of 5.0 and 7.4 days, for sites 1 and 2, respectively. From the pre-harvest residue limit curve, it was predicted that if the residues were <1.13 or 1.40 mg/kg 10 days before harvest, the residue level would be lower than the MRL during harvest. Risk assessment on day 0 showed an acceptable daily intake (%) of 13.0% and 11.0% for sites 1 and site 2, respectively, which indicates that the residual amounts are not hazardous to the Korean population.


Assuntos
Cromatografia Líquida/métodos , Resíduos de Praguicidas/análise , Piridinas/análise , Pyrus/química , Espectrometria de Massas em Tandem/métodos , Tiazinas/análise , Calibragem , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Cinética , Limite de Detecção , Neonicotinoides , Medição de Risco , Sensibilidade e Especificidade
12.
J Cell Biochem ; 117(1): 230-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26104915

RESUMO

Heat shock protein 90 (HSP90) regulates the stability of various proteins and plays an essential role in cellular homeostasis. Many client proteins of HSP90 are involved in cell growth, survival, and migration; processes that are generally accepted as participants in tumorigenesis. HSP90 is also up-regulated in certain tumors. Indeed, the inhibition of HSP90 is known to be effective in cancer treatment. Recently, studies showed that HSP90 regulates transforming growth factor ß1 (TGF-ß1)-induced transcription by increasing the stability of the TGF-ß receptor. TGF-ß signaling also has been implicated in cancer, suggesting the possibility that TGF-ß1 and HSP90 function cooperatively during the cancer cell progression. Here in this paper, we investigated the role of HSP90 in TGF-ß1-stimulated Mv1Lu cells. Treatment of Mv1Lu cells with the HSP90 inhibitor, 17-allylamino-demethoxy-geldanamycin (17AAG), or transfection with truncated HSP90 (ΔHSP90) significantly reduced TGF-ß1-induced cell migration. Pretreatment with 17AAG or transfection with ΔHSP90 also reduced the levels of phosphorylated Smad2 and Smad3. In addition, the HSP90 inhibition interfered the nuclear localization of Smads induced by constitutively active Smad2 (S2EE) or Smad3 (S3EE). We also found that the HSP90 inhibition decreased the protein level of importin-ß1 which is known to regulate R-Smad nuclear translocation. These data clearly demonstrate a novel function of HSP90; HSP90 modulates TGF-ß signaling by regulating Smads localization. Overall, our data could provide a detailed mechanism linking HSP90 and TGF-ß signaling. The extension of our understanding of HSP90 would offer a better strategy for treating cancer.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Animais , Benzoquinonas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/genética , Lactamas Macrocíclicas/farmacologia , Fosforilação/efeitos dos fármacos , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
13.
Biochem Biophys Res Commun ; 476(4): 420-425, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27237972

RESUMO

The evidence suggests that transforming growth factor-beta (TGF-ß) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-ß1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-ß1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-ß1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-ß1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-ß1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-ß type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-ß1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-ß1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression.


Assuntos
Dano ao DNA , Células Epiteliais/efeitos da radiação , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , DNA Ligase Dependente de ATP/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Raios gama , Humanos , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Proteínas Smad/genética , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Biomed Chromatogr ; 30(11): 1835-1842, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27187504

RESUMO

Lepimectin, as an emulsifiable concentrate, was sprayed on shallots at the recommended dose rate (10 mL/20 L) to determine its residue levels, dissipation pattern, pre-harvest residue limits (PHRLs), and health risk. Samples were randomly collected over 10 days, extracted with acetonitrile, purified using an amino solid-phase extraction (NH2 -SPE) cartridge and analyzed using a high-performance liquid chromatography-photodiode array detection method. Field-incurred samples were confirmed using ultra-performance liquid chromatography-tandem mass spectrometry. The linearity was excellent, with a determination coefficient (R2 ) of ≥0.9991. The recoveries at two spiking levels (0.2 and 1.0 mg/kg) ranged from 84.49 to 87.64% with relative standard deviations of ≤7.04%. The developed method was applied to field samples grown in separate greenhouses, one located in Naju and one in Muan, in the Republic of Korea. The dissipation pattern was described by first-order kinetics with half-lives of 1.9 (Naju) and 1.7 days (Muan). The PHRL curves indicated that, if the lepimectin residues are <0.18 (Naju) and <0.13 mg/kg (Muan) 5 days before harvest, the residue levels will be lower than the maximum residue limit (0.05 mg/kg) upon harvesting. The risk assessment data indicated that lepimectin is safe for use in the cultivation of shallots, with no risk of detrimental effects to the consumer.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Aditivos Alimentares/análise , Lactonas/análise , Compostos Macrocíclicos/análise , Resíduos de Praguicidas/análise , Cebolinha Branca/química , Espectrometria de Massas em Tandem/métodos , Análise de Alimentos/métodos , Limite de Detecção
15.
Hong Kong Physiother J ; 34: 10-18, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30931022

RESUMO

BACKGROUND: Children with cerebral palsy (CP) exhibit diverse gait patterns depending on their neurological deficits and musculoskeletal problems. The Adeli suit treatment (AST) has been proposed as an intensive exercise protocol in the management of CP. OBJECTIVES: The aim of this study was to compare the effects of a 6-week programme of combined AST and neurodevelopment treatment (NDT) with those of NDT alone on Gross Motor Function Measure (GMFM), balance, and gait in children with CP. METHODS: Twenty children with CP of Gross Motor Function Classification System levels I and II were randomly assigned to one of the following two groups: (1) NDT or (2) AST/NDT. The participants were assessed using the GMFM, Pediatric Balance Scale (PBS), Timed Up and Go (TUG) test, and spatiotemporal gait parameters. RESULTS: The GMFM, PBS, and TUG test for both groups showed a statistically significant increase (p < 0.05). Three children were excluded. Compared to the NDT group (n = 9), the AST/NDT group (n = 8) demonstrated a significant increase in spatiotemporal gait parameters (p < 0.05). CONCLUSION: These results provide evidence for the greater effectiveness of combined AST/NDT than NDT alone in improving spatiotemporal gait parameters but not GMFM, PBS, and TUG test.

16.
Bioorg Med Chem Lett ; 24(17): 4271-5, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25082126

RESUMO

Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate.


Assuntos
Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Descoberta de Drogas , Malonatos/farmacologia , Pirimidinas/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Animais , Disponibilidade Biológica , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Inibidores das Enzimas do Citocromo P-450/química , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Malonatos/administração & dosagem , Malonatos/química , Camundongos , Camundongos Endogâmicos ICR , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Pirimidinas/administração & dosagem , Pirimidinas/química , Relação Estrutura-Atividade
17.
Exp Cell Res ; 319(4): 466-73, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23262026

RESUMO

Transforming growth factor-ß1 (TGF-ß1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-ß1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-ß1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-ß receptors, we investigated the involvement of TGF-ß signaling in the effects of γ-irradiation. We found that canonical TGF-ß signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-ß receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-ß1. Our data thus indicate that TGF-ß1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.


Assuntos
Raios gama , Tolerância a Radiação , Fator de Crescimento Transformador beta/fisiologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Células Epiteliais/efeitos da radiação , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/efeitos da radiação , Vison , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/genética , Tolerância a Radiação/fisiologia , Protetores contra Radiação/metabolismo , Protetores contra Radiação/farmacologia , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Transfecção , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia
18.
J Nanosci Nanotechnol ; 14(8): 6231-4, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25936093

RESUMO

Poly(vinylidenefluoride-co-hexafluoropropylene) (PVDF-HFP) nanofibers containing inorganic fillers were fabricated by electrospinning. Dye-sensitized solar cells (DSSCs) using these nanofibers showed improved short circuit currents without degraded fill factors or open circuit voltages. The long-term stabilities of cells using electrospun PVDF-HFP/titanium isopropoxide (TIP) nanofibers were significantly improved.


Assuntos
Corantes/química , Fontes de Energia Elétrica , Nanofibras , Energia Solar , Microscopia Eletrônica de Varredura
19.
J Nanosci Nanotechnol ; 14(8): 6238-42, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25936095

RESUMO

We prepared electrospun polymer nanofibers by electrospnning method and investigated about their applications to dye-sensitized solar cells (DSSCs). Electrospun polymer nanofibers applied to the polymer matrix in electrolyte for DSSCs. To improve the stiffness of polymer nanofiber, poly(vinylidene fluoride-hexafluoro propylene)/Poly(methyl methacrylate) (PVDF-HFP/PMMA) blend nanofibers were prepared and examined. In the electrospun PVDF-HFP/PMMA (1:1) blend nanofibers, the best results of VOC, JSC, FF, and efficiency of the DSSC devices showed 0.71 V, 12.8 mA/cm2, 0.61, and 5.56% under AM 1.5 illumination.


Assuntos
Corantes/química , Fontes de Energia Elétrica , Eletrólitos/química , Nanofibras , Polimetil Metacrilato/química , Politetrafluoretileno/análogos & derivados , Polivinil/química , Energia Solar , Microscopia Eletrônica de Varredura , Politetrafluoretileno/química
20.
Korean Circ J ; 54(1): 1-12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38196339

RESUMO

BACKGROUND AND OBJECTIVES: The objective of this study was to estimate the supply and demand for cardiologists in Korea and provide evidence for healthcare policy to ensure a stable and adequate workforce for optimal cardiovascular disease management. METHODS: Past trends of inflow and outflow of cardiologists were used to make crude projections, which were then adjusted based on demands of services to obtain final projections. Inflow of cardiologists was estimated using second-order polynomial regression and demand for cardiology care was estimated using linear regression. RESULTS: There were 1,139 active cardiologists who were under the age of 65 in clinical practice in Korea. The estimated number of cardiologists from 2022 to 2040 showed that the number of cardiologists would peak at 1,344 in 2032 and gradually decrease thereafter. We also estimated an increase of 947,811 cases of heart-related procedures annually from 2023 to 2032. The number of heart-related procedures per cardiologist would increase 1.4 times from 12,964 in 2023 to 17,862 in 2032. The estimated number of emergency patients per cardiologist under 50 years old would almost double from 544 in 2022 to 987 in 2032. CONCLUSIONS: We expect significant shortage of cardiologists in Korea within the next 10 years. The number of emergency patients per cardiologist will increase by nearly 50%, leading to high individual workload for cardiologists. To prevent this imbalance between supply and demand, an organized and collective approach by the specialty of cardiology is imperative to produce a balanced workforce.

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