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1.
Plant Cell Environ ; 46(4): 1157-1175, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36071575

RESUMO

Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely unknown. Previous studies revealed that excessive levels of indole-3-acetic acid(IAA) frequently cause the inhibition of plant growth and development. In this study, the high-level accumulation of endogenous IAA is observed under dark submergence, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167-ARF-GH3 pathway. The OsGH3-8 encodes an IAA-amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressing OsGH3-8 increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. Our studies reveal that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.


Assuntos
Germinação , Oryza , Plântula/metabolismo , Oryza/genética , Anaerobiose , Proteínas de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas
2.
J Sports Sci ; 41(14): 1383-1392, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37885067

RESUMO

The importance of coach leadership to athlete development and performance has been identified in the literature. We respond to the call to investigate antecedents of coach transformational leadership and their indirect effects on athlete outcomes. We propose that coach extraversion as an antecedent of coach transformational leadership can indirectly impact follower cohesion and satisfaction. Building on this mediation model, we assert that educational environment (i.e., high school and university) may serve as a first-stage moderator between coach extraversion and transformational leadership. We used 48 coaches and their 570 athletes from competitive high school and university basketball teams to test this moderated mediation model. Our results indicate that coach extraversion indirectly impacts athlete cohesion and satisfaction via transformational leadership. Moreover, the indirect effects of coach extraversion on athlete outcomes via coach transformational leadership is conditionally significant only when coaches and athletes are in universities but not in high schools. Our findings highlight the importance of educational environment in determining the association between coach personality and leadership perception. Implications for research and practice are discussed.


Assuntos
Extroversão Psicológica , Liderança , Humanos , Motivação , Atletas , Personalidade
3.
Sensors (Basel) ; 22(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36081159

RESUMO

Typhoons in summer and cold snaps during winter in Taiwan often cause huge aquaculture losses. Simultaneously, the lack of human resources is a problem. Therefore, we used wireless transmission technology with various sensors to transmit the temperature, pH value, dissolved oxygen, water level, and life expectancy of the sensor in the fish farm to the server. The integrated data are transmitted to mobile devices through the Internet of Things, enabling administrators to monitor the water quality in a fish farm through mobile devices. Because the current pH sensors cannot be submerged in the liquid for a long time for measurements, human resources and time are required to take the instrument to each fish farm for testing at a fixed time. Therefore, a robotic arm was developed to complete automatic measurement and maintenance actions. We designed this arm with a programmable logic controller, a single chip combined with a wireless transmission module, and an embedded system. This system is divided into control, measurement, server, and mobility. The intelligent measurement equipment designed in this study can work 24 h per day, which effectively reduces the losses caused by personnel, material resources, and data errors.


Assuntos
Pesqueiros , Qualidade da Água , Aquicultura , Arritmias Cardíacas , Humanos , Monitorização Fisiológica , Tecnologia sem Fio
4.
J Clin Nurs ; 31(15-16): 2271-2286, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34523181

RESUMO

AIMS AND OBJECTIVES: To investigate the characteristics and prevalence of demoralisation syndrome among heart transplantation patients in Taiwan. BACKGROUND: Patients with end-stage heart failure who have undergone cardiac transplantation are at risk of demoralisation syndrome. Demoralisation syndrome has been studied in cancer populations, but our understanding of the syndrome among heart transplant recipients is limited. DESIGN AND METHODS: The study adopted a cross-sectional design and analysed the baseline data from a longitudinal study with cardiac transplant patients at a heart centre in northern Taiwan. A structured questionnaire, namely the Demoralization Scale-Mandarin Version (DS-MV), was used to assess demoralisation syndrome. Hierarchical regression was applied to determine the predictors of demoralisation. Reporting was consistent with the STROBE checklist. RESULTS: There were a total of 84 participants with an average age of 51.9 years and a time since heart transplantation of around 4.1 years. Among them, the prevalence of demoralisation syndrome was 35.8%, and 57.1% coped well with stress. In addition, on the DS-MV, participants tended to choose sentences with positive rather than negative wording. Our data showed that cardiac transplant recipients with stress have higher possibility suffering from demoralisation syndrome; poor renal function and those who cannot relive from stress are predictors for loss of meaning. CONCLUSIONS: Chinese individuals tend to hide their weaknesses; nevertheless, demoralisation syndrome among cardiac transplant recipients, as related to stress status and kidney function, is still remarkable. RELEVANCE TO CLINICAL PRACTICE: Since demoralisation is preventable, further research on this phenomenon in the cardiac transplant population is warranted and needs to be developed.


Assuntos
Desmoralização , Transplante de Coração , Estudos Transversais , Transplante de Coração/efeitos adversos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Inquéritos e Questionários , Síndrome
5.
J Sch Nurs ; : 10598405221112695, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35833344

RESUMO

Alcohol use ranks as one of the most prevalent health-risk behaviors among Taiwanese adolescents. Possible selves-personalized future-oriented cognitions about the self-are significant motivators of one's actions, which may potentially influence adolescent drinking behavior. This study aimed to estimate the content domain-specific possible selves and their associations with drinking behaviors among Taiwanese adolescents. A total of 225 Taiwanese seventh and eighth graders from a public junior high school were recruited. An anonymous self-reported questionnaire was used to collect data during two time-points at six-month intervals. Results showed that having a "physical appearance" related hoped-for possible self and a "friendship" related feared possible self was associated with adolescent alcohol use after six months. Whereas, having the "physical appearance" related hoped-for and feared possible selves were associated with alcohol problems, at both, baseline and six months later. Future studies could clarify the meaning behind "physical appearance" related possible selves.

6.
Molecules ; 27(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35011311

RESUMO

The components of OLED encapsulation with hermetic sealing and a 1026-day lifetime were measured by PXI-1033. The optimal characteristics were obtained when the thickness of the TPBi layer was 20 nm. This OLED obtained a maximum luminance (Lmax) of 25,849 cd/m2 at a current density of 1242 mA/cm2, an external quantum efficiency (EQE) of 2.28%, a current efficiency (CE) of 7.20 cd/A, and a power efficiency (PE) of 5.28 lm/W. The efficiency was enhanced by Lmax 17.2%/EQE 0.89%/CE 42.1%/PE 41.9%. The CIE coordinates of 0.32, 0.54 were all green OLED elements with wavelengths of 532 nm. The shear strain and leakage test gave results of 16 kgf and 8.92 × 10-9 mbar/s, respectively. The reliability test showed that the standard of MIL-STD-883 was obtained.

7.
Molecules ; 25(20)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086589

RESUMO

Single photon emission computed tomography (SPECT) has been employed to detect Parkinson's disease (PD). However, analysis of the SPECT PD images was mostly based on the region of interest (ROI) approach. Due to limited size of the ROI, especially in the multi-stage classification of PD, this study utilizes deep learning methods to establish a multiple stages classification model of PD. In the retrospective study, the 99mTc-TRODAT-1 was used for brain SPECT imaging. A total of 202 cases were collected, and five slices were selected for analysis from each subject. The total number of images was thus 1010. According to the Hoehn and Yahr Scale standards, all the cases were divided into healthy, early, middle, late four stages, and HYS I~V six stages. Deep learning is compared with five convolutional neural networks (CNNs). The input images included grayscale and pseudo color of two types. The training and validation sets were 70% and 30%. The accuracy, recall, precision, F-score, and Kappa values were used to evaluate the models' performance. The best accuracy of the models based on grayscale and color images in four and six stages were 0.83 (AlexNet), 0.85 (VGG), 0.78 (DenseNet) and 0.78 (DenseNet).


Assuntos
Encéfalo/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Doença de Parkinson/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Encéfalo/fisiopatologia , Corpo Estriado/fisiopatologia , Aprendizado Profundo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Doença de Parkinson/classificação , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Estudos Retrospectivos , Tecnécio/uso terapêutico
8.
Sensors (Basel) ; 19(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978990

RESUMO

The neuroimaging techniques such as dopaminergic imaging using Single Photon Emission Computed Tomography (SPECT) with 99mTc-TRODAT-1 have been employed to detect the stages of Parkinson's disease (PD). In this retrospective study, a total of 202 99mTc-TRODAT-1 SPECT imaging were collected. All of the PD patient cases were separated into mild (HYS Stage 1 to Stage 3) and severe (HYS Stage 4 and Stage 5) PD, according to the Hoehn and Yahr Scale (HYS) standard. A three-dimensional method was used to estimate six features of activity distribution and striatal activity volume in the images. These features were skewness, kurtosis, Cyhelsky's skewness coefficient, Pearson's median skewness, dopamine transporter activity volume, and dopamine transporter activity maximum. Finally, the data were modeled using logistic regression (LR) and support vector machine (SVM) for PD classification. The results showed that SVM classifier method produced a higher accuracy than LR. The sensitivity, specificity, PPV, NPV, accuracy, and AUC with SVM method were 0.82, 1.00, 0.84, 0.67, 0.83, and 0.85, respectively. Additionally, the Kappa value was shown to reach 0.68. This claimed that the SVM-based model could provide further reference for PD stage classification in medical diagnosis. In the future, more healthy cases will be expected to clarify the false positive rate in this classification model.


Assuntos
Corpo Estriado/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Máquina de Vetores de Suporte , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Dopamina/química , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio/administração & dosagem , Doença de Parkinson/classificação , Doença de Parkinson/diagnóstico , Doença de Parkinson/patologia , Estudos Retrospectivos , Tropanos/administração & dosagem
9.
Plant Cell Environ ; 40(9): 1735-1747, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28437590

RESUMO

Light controls vegetative and reproductive development of plants. For a plant, sensing the light input properly ensures coordination with the ever-changing environment. Previously, we found that LIGHT-REGULATED WD1 (LWD1) and LWD2 regulate the circadian clock and photoperiodic flowering. Here, we identified Arabidopsis YET ANOTHER KINASE1 (AtYAK1), an evolutionarily conserved protein and a member of dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), as an interacting protein of LWDs. Our study revealed that AtYAK1 is an important regulator for various light responses, including the circadian clock, photomorphogenesis and reproductive development. AtYAK1 could antagonize the function of LWDs in regulating the circadian clock and photoperiodic flowering. By examining phenotypes of atyak1, we found that AtYAK1 regulated light-induced period-length shortening and photomorphogenic development. Moreover, AtYAK1 mediated plant fertility especially under inferior light conditions including low light and short-day length. This study discloses a new regulator connecting environmental light to plant growth.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/crescimento & desenvolvimento , Luz , Desenvolvimento Vegetal/efeitos da radiação , Proteínas Serina-Treonina Quinases/metabolismo , Arabidopsis/efeitos da radiação , Ritmo Circadiano/efeitos da radiação , Flores/fisiologia , Flores/efeitos da radiação , Morfogênese/efeitos da radiação , Mutação/genética , Fosforilação/efeitos da radiação , Fotoperíodo , Infertilidade das Plantas/efeitos da radiação , Ligação Proteica/efeitos da radiação , Especificidade por Substrato/efeitos da radiação
10.
Int J Nurs Pract ; 23(1)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28066961

RESUMO

The purpose of this study was to understand the lifestyle; examine the relationships among lifestyle, medical factors, and stress status; and determine the predictors of better lifestyle in heart transplant recipients in Taiwan. A prospective design with convenience sampling was used. Data were collected through the Health-Promoting Lifestyle Profile-II and demographic questionnaires, which included personal information, stress status, and medical information. Pearson correlations, 1-way analysis of variance, independent t tests, paired t tests, and hierarchical regression were used to analyze the factors related to better lifestyle. A total of 80 heart transplant recipients participated. The mean score for lifestyle decreased from baseline to 3 months and was even lower at 6 months. Nevertheless, the trend for some participants was the opposite-their lifestyle improved over the 6-month period after baseline. Notably, the trend for each of the 6 subscales was not consistent with the mean of the total score. Stress status accounted for 12.8% of lifestyle. When stress status was combined with family income and creatinine, the 3 factors accounted for 32.2% of lifestyle. This study demonstrated that maintenance of a healthy lifestyle fluctuates after transplantation. Demographic factors and stress status can help to identify people who are more likely to have a poor lifestyle.


Assuntos
Transplante de Coração , Estilo de Vida , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos , Inquéritos e Questionários , Taiwan
11.
J Transl Med ; 14: 38, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26847768

RESUMO

BACKGROUND: The heterogeneous and dynamic tumor microenvironment has significant impact on cancer cell proliferation, invasion, drug response, and is probably associated with entering dormancy and recurrence. However, these complex settings are hard to recapitulate in vitro. METHODS: In this study, we mimic different restriction forces that tumor cells are exposed to using a physiologically relevant 3D model with tunable mechanical stiffness. RESULTS: Breast cancer MDA-MB-231, colon cancer HCT-116 and pancreatic cancer CFPAC cells embedded in the stiffer gels exhibit a changed morphology and cluster formation, prolonged doubling time, and a slower metabolism rate, recapitulating the pathway from competency to dormancy. Altering environmental restriction allows them to re-enter and exit dormant conditions and change their sensitivities to drugs such as paclitaxol and gemcitabine. Cells surviving drug treatments can still regain competent growth and form tumors in vivo. CONCLUSION: We have successfully developed an in vitro 3D model to mimic the effects of matrix restriction on tumor cells and this high throughput model can be used to study tumor cellular functions and their drug responses in their different states. This all in one platform may aid effective drug development.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Camundongos Nus , Modelos Biológicos , Neoplasias/metabolismo , Oxirredução/efeitos dos fármacos , Ratos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Plant Cell ; 25(10): 3699-710, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24179124

RESUMO

Translational control plays a vital role in regulating gene expression. To decipher the molecular basis of translational regulation in photomorphogenic Arabidopsis thaliana, we adopted a ribosome profiling method to map the genome-wide positions of translating ribosomes in Arabidopsis etiolated seedlings in the dark and after light exposure. We found that, in Arabidopsis, a translating ribosome protects an ~30-nucleotide region and moves in three-nucleotide periodicity, characteristics also observed in Saccharomyces cerevisiae and mammals. Light enhanced the translation of genes involved in the organization and function of chloroplasts. Upstream open reading frames initiated by ATG but not CTG mediated translational repression of the downstream main open reading frame. Also, we observed widespread translational repression of microRNA target genes in both light- and dark-grown Arabidopsis seedlings. This genome-wide characterization of transcripts undergoing translation at the nucleotide-resolution level reveals that a combination of multiple translational mechanisms orchestrates and fine-tunes the translation of diverse transcripts in plants with environmental responsiveness.


Assuntos
Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Morfogênese/genética , Biossíntese de Proteínas , Ribossomos/genética , Arabidopsis/efeitos da radiação , Mapeamento Cromossômico , Códon de Iniciação , Biblioteca Gênica , Luz , MicroRNAs/genética , Morfogênese/efeitos da radiação , Fases de Leitura Aberta , RNA Mensageiro/genética , RNA de Plantas/genética , Análise de Sequência de RNA
13.
Int J Mol Sci ; 17(11)2016 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-27827952

RESUMO

Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Proteínas de Ligação a DNA/genética , Receptores ErbB/genética , Queratina-7/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Proto-Oncogênicas c-ets/genética , RNA Neoplásico/genética , Receptor EphB4/genética , Fatores de Transcrição/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Proteínas de Ligação a DNA/sangue , Receptores ErbB/sangue , Feminino , Humanos , Separação Imunomagnética/métodos , Queratina-7/sangue , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-ets/sangue , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Neoplásico/sangue , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptor EphB4/sangue , Análise de Sobrevida , Fatores de Transcrição/sangue
14.
Lab Invest ; 95(12): 1398-408, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26367487

RESUMO

miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR-21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR-21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis. The suppression of miR-21 in metastatic SACC-LM cells significantly increased the report activity of PDCD4 promoter and the expression of PDCD4 protein. This subsequently resulted in downregulation of the p-STAT3 protein. The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in SACC specimens, respectively, indicating the potential role of the STAT3-miR-21-PDCD4 pathway in these tumors. Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4. Therefore, suppression of miR-21 may provide a potential approach for the treatment of advanced SACC patients.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Adenoide Cístico/metabolismo , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Carcinoma Adenoide Cístico/mortalidade , Estudos de Casos e Controles , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias das Glândulas Salivares/mortalidade
15.
Brain Behav Immun ; 43: 118-29, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25135858

RESUMO

Neuroinflammation is known to be involved in epileptogenesis with unclear mechanisms. Inhibition of soluble epoxide hydrolase (sEH) seems to offer anti-inflammatory protection to ischemic brain injury in rodents. Thus, it is hypothesized that sEH inhibition might also affect the neuroinflammatory responses caused by epileptic seizures. In the present study, we investigated the involvement of sEH in neuroinflammation, seizure generation and subsequent epileptogenesis using two mouse models of temporal lobe epilepsy. Experimental epileptic seizures were induced by either pilocarpine or electrical amygdala kindling in both wild-type (WT) C57BL/6 mice and sEH knockout (sEH KO) mice. The sEH expression in the hippocampus was detected by immunohistochemistry and Western blot analysis. The effects of the sEH hydrolase inhibitors, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU), and of the genetic deletion of sEH on seizure-induced neuroinflammatory responses and the development of epilepsy were evaluated. In the hippocampus of WT mice, sEH was mainly expressed in astrocytes (GFAP(+)), neurons (NeuN(+)) and scattered microglia (Iba-1(+)) in the regions of CA1, CA3 and dentate gyrus. Expression of sEH was significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus (SE). Administration with sEH inhibitors attenuated the SE-induced up-regulation of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), the degradation of EETs, as well as IκB phosphorylation. Following treatment with AUDA, the frequency and duration of spontaneous motor seizures in the pilocarpine-SE mice were decreased and the seizure-induction threshold of the fully kindled mice was increased. Up-regulation of hippocampal IL-1ß and IL-6 was found in both WT and sEH KO mice after successful induction of SE. Notably, sEH KO mice were more susceptible to seizures than WT mice. Seizure related neuroinflammation and ictogenesis were attenuated by pharmacological inhibition of sEH enzymatic activity but not by sEH genetic deletion. Therefore, sEH may play an important role in the generation of epilepsy. Furthermore, the effectiveness of AUDA in terms of anti-inflammatory and anti-ictogenesis properties suggests that it may have clinical therapeutic implication for epilepsy in the future, particularly when treating temporal lobe epilepsy.


Assuntos
Epilepsia do Lobo Temporal/metabolismo , Epóxido Hidrolases/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Excitação Neurológica/metabolismo , Convulsões/metabolismo , Animais , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/etiologia , Epóxido Hidrolases/genética , Interleucina-1beta , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pilocarpina , Convulsões/etiologia , Regulação para Cima
16.
Int J Mol Sci ; 16(5): 9831-49, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25941928

RESUMO

In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR⁻/⁻) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR⁻/⁻ mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR⁺/⁺) oocytes had reached metaphase II. Interestingly, we found these AR⁻/⁻ female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-ß (PGC1-ß) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-ß-mediated mitochondrial biogenesis in granulosa cells.


Assuntos
Diferenciação Celular , Células da Granulosa/patologia , Mitocôndrias/metabolismo , Receptores Androgênicos/deficiência , Animais , Forma Celular , Estradiol/sangue , Feminino , Genótipo , Células da Granulosa/metabolismo , Células da Granulosa/ultraestrutura , Técnicas de Maturação in Vitro de Oócitos , Potencial da Membrana Mitocondrial , Camundongos Knockout , Mitocôndrias/ultraestrutura , Oócitos/metabolismo , Biogênese de Organelas , Receptores Androgênicos/metabolismo , Reprodutibilidade dos Testes
17.
Toxicol Appl Pharmacol ; 278(3): 249-58, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24823293

RESUMO

DNA damage has been shown to induce autophagy, but the role of autophagy in the DNA damage response and cell fate is not fully understood. BO-1012, a bifunctional alkylating derivative of 3a-aza-cyclopenta[a]indene, is a potent DNA interstrand cross-linking agent with anticancer activity. In this study, BO-1012 was found to reduce DNA synthesis, inhibit S phase progression, and induce phosphorylation of histone H2AX on serine 139 (γH2AX) exclusively in S phase cells. Both CHK1 and CHK2 were phosphorylated in response to BO-1012 treatment, but only depletion of CHK1, but not CHK2, impaired BO-1012-induced S phase arrest and facilitated the entry of γH2AX-positive cells into G2 phase. CHK1 depletion also significantly enhanced BO-1012-induced cell death and apoptosis. These results indicate that BO-1012-induced S phase arrest is a CHK1-dependent pro-survival response. BO-1012 also resulted in marked induction of acidic vesicular organelle (AVO) formation and microtubule-associated protein 1 light chain 3 (LC3) processing and redistribution, features characteristic of autophagy. Depletion of ATG7 or co-treatment of cells with BO-1012 and either 3-methyladenine or bafilomycin A1, two inhibitors of autophagy, not only reduced CHK1 phosphorylation and disrupted S phase arrest, but also increased cleavage of caspase-9 and PARP, and cell death. These results suggest that cells initiate S phase arrest and autophagy as pro-survival responses to BO-1012-induced DNA damage, and that suppression of autophagy enhances BO-1012-induced apoptosis via disruption of CHK1-dependent S phase arrest.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma/tratamento farmacológico , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Proteínas Quinases/metabolismo , Antineoplásicos Alquilantes/agonistas , Proteína 7 Relacionada à Autofagia , Carbamatos/agonistas , Carbamatos/farmacologia , Carcinoma/enzimologia , Carcinoma/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quinase 1 do Ponto de Checagem , Classe III de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Reagentes de Ligações Cruzadas/farmacologia , Feminino , Inativação Gênica , Células HeLa , Compostos Heterocíclicos com 3 Anéis/agonistas , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Indenos/agonistas , Indenos/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Quinases/química , Proteínas Quinases/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Fase S/efeitos dos fármacos , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , ATPases Vacuolares Próton-Translocadoras/metabolismo
18.
Dig Dis Sci ; 59(6): 1160-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24385013

RESUMO

BACKGROUND AND AIM: Aberrant DNA methylation has been shown to be associated with the growth, development, metastasis, and prognosis of tumors. Methylated DNAs may be suitable biomarkers for cancer patients. Here, we investigated whether circulating methylated MINT2 DNAs represent a potential poor prognostic factor in gastric cancer (GC). METHODS: MINT2 methylation was detected by real-time methylation-specific PCR in tumor tissues, pairing preoperative peritoneal lavage fluid (PPLF) and blood from 92 GC patients. The theory meaning and clinical practicality value of MINT2 methylation in different specimens were analyzed. RESULTS: The methylation status of the MINT2 gene was found to be significantly higher in tumor tissues (44.6%, 41/92) than in adjacent normal tissues (3.3%, 3/92). No MINT2 methylation was found in healthy controls, and partial MINT2 methylation was observed in three (6.25%, 3/48) patients with chronic atrophic gastritis. The frequency of MINT2 methylation in pairing PPLF and blood samples from 92 GC patients was 40.2% (37/92) and 39.1% (36/92), respectively. Methylated MINT2 in tumor tissues, pairing PPLF, and blood samples were very approximate. Aberrant MINT2 methylation in tumor tissues and pairing PPLF or blood samples were closely related to peritoneal dissemination, tumor progression, and poor prognosis (all P < 0.0001). CONCLUSIONS: Aberrant MINT2 methylation in PPLF/blood may predict peritoneal micrometastasis for GC patients, which is a potential poor prognostic factor in GC.


Assuntos
Biomarcadores Tumorais/sangue , Caderinas/metabolismo , Proteínas de Transporte/metabolismo , DNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Regiões Promotoras Genéticas/fisiologia , Neoplasias Gástricas/metabolismo , Caderinas/genética , Proteínas de Transporte/genética , Ilhas de CpG , DNA/sangue , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Sensibilidade e Especificidade , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia
19.
Virus Res ; 344: 199359, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38521505

RESUMO

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.


Assuntos
Vírus da Febre Suína Africana , Antivirais , DNA Polimerase Dirigida por DNA , Vírus da Febre Suína Africana/efeitos dos fármacos , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/química , Animais , Antivirais/farmacologia , Antivirais/química , Febre Suína Africana/virologia , Suínos , Descoberta de Drogas , Replicação Viral/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ligação Proteica , Simulação de Acoplamento Molecular , DNA Viral/genética , Farmacóforo
20.
Am J Intellect Dev Disabil ; 129(2): 151-168, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411244

RESUMO

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.


Assuntos
Deficiência Intelectual , Motivação , Criança , Humanos , Adolescente , Objetivos , Deficiências do Desenvolvimento , Pais , Emprego
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