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1.
Inorg Chem ; 58(4): 2336-2345, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30730725

RESUMO

The modulation of the reactivity of metal oxo species by redox inactive metals has attracted much interest due to the observation of redox inactive metal effects on processes involving electron transfer both in nature (the oxygen-evolving complex of Photosystem II) and in heterogeneous catalysis (mixed-metal oxides). Studies of small-molecule models of these systems have revealed numerous instances of effects of redox inactive metals on electron- and group-transfer reactivity. However, the heterometallic species directly involved in these transformations have rarely been structurally characterized and are often generated in situ. We have previously reported the preparation and structural characterization of multiple series of heterometallic clusters based on Mn3 and Fe3 cores and described the effects of Lewis acidity of the heterometal incorporated in these complexes on cluster reduction potential. To determine the effects of Lewis acidity of redox inactive metals on group transfer reactivity in structurally well-defined complexes, we studied [Mn3MO4], [Mn3MO(OH)], and [Fe3MO(OH)] clusters in oxygen atom transfer (OAT) reactions with phosphine substrates. The qualitative rate of OAT correlates with the Lewis acidity of the redox inactive metal, confirming that Lewis acidic metal centers can affect the chemical reactivity of metal oxo species by modulating cluster electronics.

2.
Cancer Res Treat ; 51(1): 150-157, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29621877

RESUMO

PURPOSE: Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens. Materials and Methods: Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen. RESULTS: Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response. CONCLUSION: Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Variações do Número de Cópias de DNA/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4/genética , Linfoma de Células T/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacologia , DNA Viral/efeitos dos fármacos , DNA Viral/genética , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/virologia , Etoposídeo/administração & dosagem , Etoposídeo/farmacologia , Feminino , Herpesvirus Humano 4/efeitos dos fármacos , Humanos , Contagem de Linfócitos , Linfoma de Células T/sangue , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/farmacologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/farmacologia
3.
Ann Hematol ; 98(2): 255-269, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30368587

RESUMO

Diffuse large B cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma (NHL), is a clinically and molecularly heterogeneous malignant lymphoproliferative disease. In the era of personalized medicine, genetic information is critical to early diagnosis, aiding risk stratification, directing therapeutic option, and monitoring disease relapse. However, lacking a circulating disease with most DLBCL cases hampers the acquisition of tumor genomic landscapes and disease dynamics. Circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker, reliably reflecting the comprehensive tumor genetic profiles, thus holds great promise in individualized medicine, including precise diagnosis and prognosis, response monitoring, and relapse detection of DLBCL. Here, we reviewed the recent advances of ctDNA in DLBCL and discussed its clinical values at different time points during the disease courses by comparing with the current routine methods in clinical practice. Collectively, we anticipated that ctDNA will ultimately be integrated into the management of DLBCL to facilitate precision medicine.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Linfoma Difuso de Grandes Células B/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(2): 382-388, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29665902

RESUMO

OBJECTIVE: The past studies found that the treatment of chronic myeloid leukemia (CML) with imatinib can induce the macrocytic anemia, moreover the incidence of anemia increases along with enhancement of imatinib concentration. This study was aimed to evaluate the potential relation of erythrocyte mean corpuscular volume (MCV) increase after the treatment with tyrosine kinase inhibitors (TKI) with the therapeutic response in patients with CML-chronic phase (CML-CP). METHODS: The clinical and hematologic data including MCV, molecular and cytogenetic response of 119 patients with CML-CP were collected after treatment with TKIs, and the relation of MCV changes after treatment with the clinical characteristics and therapeutic efficacy for patients with CML-CP was analyzed. RESULTS: The MCV in patients treated with TKIs for 12 months significantly increased as compared with that at initial diagnosis (P<0.05). The proportion of patients with increased MCV in group of complete cytogenetic response (CCyR) was significantly higher than that in group of non-CCyR (P<0.05). As compared with decreased MCV group, the patients in increased MCV group much more easily achieved CCyR after treatment for 6, 12 months (P<0.05, P<0.05) respectively, furthermore, much more easily maintained MMR (P<0.05). CONCLUSION: The MCV as a parameter which is easily acquired may be a new marker for prodecting the therapeutic response of patients treated with TKIs.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos , Índices de Eritrócitos , Humanos , Mesilato de Imatinib , Inibidores de Proteínas Quinases , Resultado do Tratamento
5.
Oncogene ; 37(21): 2837-2849, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29511345

RESUMO

Resistance to the BCR-ABL tyrosine kinase inhibitor (TKI) remains a challenge for curing the disease in chronic myeloid leukemia (CML) patients as leukemia cells may survive through BCR-ABL kinase activity-independent signal pathways. To gain insight into BCR-ABL kinase activity-independent mechanisms, we performed an initial bioinformatics screen and followed by a quantitative PCR screen of genes that were elevated in CML samples. A total of 33 candidate genes were identified to be highly expressed in TKIs resistant patients. Among those genes, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), controlling the limiting step of glycolysis, was found to be strongly associated with TKIs resistance. PFKFB3 knockdown or pharmacological inhibition of its kinase activity markedly enhanced the sensitivity of CML cells to TKIs. Furthermore, pharmacological inhibition of PFKFB3 inhibited CML cells growth and significantly prolonged the survival of both allograft and xenograft CML mice. ChIP-seq data analysis combined with subsequent knockdown experiment showed that the Ets transcription factor PU.1 regulated the elevated expression of PFKFB3 in TKIs-resistant CML cells. Therefore, our results showed that targeting PFKFB3 sensitizes CML cells to TKIs and PFKFB3 may be a potential BCR-ABL kinase activity-independent mechanism in CML.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Fosfofrutoquinase-2/genética , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Animais , Antígenos de Superfície/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/farmacologia , Células Jurkat , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Int J Aging Hum Dev ; 86(4): 382-400, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28990394

RESUMO

We examined effects of life stress and control beliefs on a constellation of subjective indicators of well-being for older people, including meaning in life, happiness, peace of mind, and positive aging perception. The Chinese cultural background provided the sociocultural milieu for the present study. In a longitudinal study, 301 older Chinese adults completed a questionnaire survey twice, 6 months apart. Regression analyses found that stress caused by major life-changing events (acute) and financial hardship (chronic) were consistent negative predictors of all well-being indicators. Furthermore, primary control belief (tenacious goal pursuit) amplified the negative impacts of life events on happiness and peace of mind. Secondary control belief (submitting to circumstances), in contrast, acted as a buffer that alleviated the deleterious effects of financial hardship on peace of mind and meaning in life. Noting the threats of unfavorable life circumstances and the potency of secondary control belief for older Chinese people, theoretical and cultural implications were discussed.


Assuntos
Envelhecimento/psicologia , Status Econômico , Controle Interno-Externo , Acontecimentos que Mudam a Vida , Satisfação Pessoal , Estresse Psicológico/psicologia , Idoso , China , Feminino , Humanos , Estudos Longitudinais
7.
Oncotarget ; 8(37): 62793-62802, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977989

RESUMO

6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases (PFKFBs) are bifunctional enzymes which regulate the transformation between fructose-2, 6-bisphosphate (F2, 6BP) and fructose-6-phosphate (F6P) in the process of glucose metabolism. Among the four isozymes (PFKFB1-4), PFKFB3 has stronger kinase activity than phosphatase activity, resulting in the synthesis of F2, 6BP and the promotion of glycolysis. Additionally, PFKFB3 plays a key role in cell cycle regulation. It has been confirmed that PFKFB3 is upregulated in a variety of tumor cells, and inhibition of it results in suppression of the growth of tumor cells by downregulating the glycolytic flux. It is expected to release drug resistance and prevent disease progression by PFKFB3 inhibition. Recent studies have also shown that the efficacy of PFKFB3 inhibition in tumor cells is not only related to glycolysis, but also autophagy. Here, we have reviewed the biological characteristics of PFKFB3, the regulation pathway of glucose metabolism manipulated by PFKFB3, and other regulatory mechanisms in hematologic and non-hematologic malignant tumor cells.

8.
J Diabetes Res ; 2017: 3164027, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28913362

RESUMO

[This corrects the article DOI: 10.1155/2016/4596316.].

9.
Invest Ophthalmol Vis Sci ; 57(15): 6747-6756, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27978555

RESUMO

Purpose: The purpose of the study is to understand how extracellular stresses, such as ultraviolet (UV) irradiation, affect corneal epithelial cells. Cell volume changes, damage to corneal epithelial integrity, and cellular responses were assessed after exposure to UVC stresses. Methods: Primary human and rabbit corneal epithelial cells were exposed to UVC light in culture conditions. Ultraviolet C irradiation-induced changes in cell size and volume were measured by real-time microscopy and self-quenching of the fluorescent dye calcein, respectively. The effects of UVC irradiation on Src and focal adhesion kinase (FAK) phosphorylation and FAK-dependent integrin signaling were detected by ELISA, immunoblotting, and immunostaining. Results: Ultraviolet C irradiation induced both size and volume shifts in human and rabbit corneal epithelial cells. Ultraviolet C irradiation-induced decrease of cell volume elicited activation of Src and FAK, characterized by increased phosphorylations of SrcY416, FAKY397, and FAKY925. In addition, immunostaining studies showed UVC irradiation-induced increases in phosphorylation of FAK and formation of integrin ß5 clustering. Application of Kv channel blockers, including 4-aminopyridine (4-AP), α-DTX, and depressing substance-1 (BDS-1), effectively suppressed UVC irradiation-induced cell volume changes, and subsequently inhibited UVC irradiation-induced phosphorylation of Src/FAK, and formation of integrin ß5 clustering, suggesting UVC irradiation-induced volume changes and Src/FAK activation. Hyperosmotic pressure-induced volume decreases were measured in comparison with effects of UVC irradiation on volume and Src/FAK activation. However, Kv channel blocker, 4-AP, had no effect on hyperosmotic pressure-induced responses. Conclusions: The present study demonstrates that UVC irradiation-induced decreases in cell volume lead to Src/FAK activation due to a rapid loss of K ions through membrane Kv channels.


Assuntos
Epitélio Anterior/citologia , Raios Ultravioleta , Animais , Western Blotting , Movimento Celular , Tamanho Celular/efeitos da radiação , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Epitélio Anterior/metabolismo , Epitélio Anterior/efeitos da radiação , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Fosforilação/efeitos da radiação , Coelhos , Quinases da Família src/metabolismo
10.
PLoS One ; 11(9): e0162071, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27583466

RESUMO

BACKGROUND: The purpose of the study is to elicit the epigenetic mechanism involving CCCTC binding factor (CTCF)-mediated chromatin remodeling that regulates PAX6 gene interaction with differentiation-associated genes to control corneal epithelial differentiation. METHODS: Cell cycle progression and specific keratin expressions were measured to monitor changes of differentiation-induced primary human limbal stem/progenitor (HLS/P), human corneal epithelial (HCE) and human telomerase-immortalized corneal epithelial (HTCE) cells. PAX6-interactive and differentiation-associated genes in chromatin remodeling mediated by the epigenetic factor CTCF were detected by circular chromosome conformation capture (4C) and ChIP (Chromatin immunoprecipitation)-on-chip approaches, and verified by FISH (Fluorescent in situ hybridization). Furthermore, CTCF activities were altered by CTCF-shRNA to study the effect of CTCF on mediating interaction of Pax6 and differentiation-associated genes in corneal epithelial cell fate. RESULTS: Our results demonstrated that differentiation-induced human corneal epithelial cells expressed typical corneal epithelial characteristics including morphological changes, increased keratin12 expression and G0/G1 accumulations. Expressions of CTCF and PAX6 were suppressed and elevated following the process of differentiation, respectively. During corneal epithelial cell differentiation, differentiation-induced RCN1 and ADAM17 were found interacting with PAX6 in the process of CTCF-mediated chromatin remodeling detected by 4C and verified by ChIP-on-chip and FISH. Diminished CTCF mRNA with CTCF-shRNA in HTCE cells weakened the interaction of PAX6 gene in controlling RCN1/ADAM17 and enhanced early onset of the genes in cell differentiation. CONCLUSION: Our results explain how epigenetic factor CTCF-mediated chromatin remodeling regulates interactions between eye-specific PAX6 and those genes that are induced/associated with cell differentiation to modulate corneal epithelial cell-specific differentiation.


Assuntos
Diferenciação Celular , Epitélio Anterior/citologia , Epitélio Anterior/metabolismo , Regulação da Expressão Gênica , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX6/metabolismo , Proteínas Repressoras/metabolismo , Fator de Ligação a CCCTC , Ciclo Celular , Linhagem Celular , Cromatina/metabolismo , Epistasia Genética , Humanos , Queratinas/metabolismo , Especificidade de Órgãos
11.
Sensors (Basel) ; 16(7)2016 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-27447641

RESUMO

Chan Ding training is beneficial to health and emotional wellbeing. More and more people have taken up this practice over the past few years. A major training method of Chan Ding is to focus on the ten Mailuns, i.e., energy points, and to maintain physical stillness. In this article, wireless wearable accelerometers were used to detect physical stillness, and the created physical stillness index (PSI) was also shown. Ninety college students participated in this study. Primarily, accelerometers used on the arms and chest were examined. The results showed that the PSI values on the arms were higher than that of the chest, when participants moved their bodies in three different ways, left-right, anterior-posterior, and hand, movements with natural breathing. Then, they were divided into three groups to practice Chan Ding for approximately thirty minutes. Participants without any Chan Ding experience were in Group I. Participants with one year of Chan Ding experience were in Group II, and participants with over three year of experience were in Group III. The Chinese Happiness Inventory (CHI) was also conducted. Results showed that the PSI of the three groups measured during 20-30 min were 0.123 ± 0.155, 0.012 ± 0.013, and 0.001 ± 0.0003, respectively (p < 0.001 ***). The averaged CHI scores of the three groups were 10.13, 17.17, and 25.53, respectively (p < 0.001 ***). Correlation coefficients between PSI and CHI of the three groups were -0.440, -0.369, and -0.537, respectively (p < 0.01 **). PSI value and the wearable accelerometer that are presently available on the market could be used to evaluate the quality of the physical stillness of the participants during Chan Ding practice.


Assuntos
Acelerometria/métodos , Braço , Técnicas Biossensoriais/métodos , Monitorização Ambulatorial/métodos , Tórax , Humanos , Saúde Mental
12.
J Biol Chem ; 291(32): 16519-29, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27281822

RESUMO

Hypoxic conditions in the cornea affect epithelial function by activating Polo-like kinase 3 (Plk3) signaling and the c-Jun·AP-1 transcription complex, resulting in apoptosis of corneal epithelial cells. Hypoxic stress in the culture conditions also regulates limbal stem cell growth and fate. In this study, we demonstrate that there is a differential response of Plk3 in hypoxic stress-induced primary human limbal stem (HLS) and corneal epithelial (HCE) cells, resulting in different pathways of cell fate. We found that hypoxic stress induced HLS cell differentiation by down-regulating Plk3 activity at the transcription level, which was opposite to the effect of hypoxic stress on Plk3 activation to elicit HCE cell apoptosis, detected by DNA fragmentation and TUNEL assays. Hypoxic stress-induced increases in c-Jun phosphorylation/activation were not observed in HLS cells because Plk3 expression and activity were suppressed in hypoxia-induced HLS cells. Instead, hypoxic stress-induced HLS cell differentiation was monitored by cell cycle analysis and measured by the decrease and increase in p63 and keratin 12 expression, respectively. Hypoxic stress-induced Plk3 signaling to regulate c-Jun activity, resulting in limbal stem cell differentiation and center epithelial apoptosis, was also found in the corneas of wild-type and Plk3(-/-)-deficient mice. Our results, for the first time, reveal the differential effects of hypoxic stress on Plk3 activity in HLS and HCE cells. Instead of apoptosis, hypoxic stress suppresses Plk3 activity to protect limbal stem cells from death and to allow the process of HLS cell differentiation.


Assuntos
Diferenciação Celular , Epitélio Anterior/enzimologia , Regulação Enzimológica da Expressão Gênica , Proteínas Serina-Treonina Quinases/biossíntese , Células-Tronco/enzimologia , Adulto , Idoso , Animais , Apoptose , Hipóxia Celular , Fragmentação do DNA , Epitélio Anterior/citologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Células-Tronco/citologia , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
13.
J Comput Graph Stat ; 25(1): 301-320, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27217713

RESUMO

Optional Pólya tree (OPT) is a flexible nonparametric Bayesian prior for density estimation. Despite its merits, the computation for OPT inference is challenging. In this paper we present time complexity analysis for OPT inference and propose two algorithmic improvements. The first improvement, named limited-lookahead optional Pólya tree (LL-OPT), aims at accelerating the computation for OPT inference. The second improvement modifies the output of OPT or LL-OPT and produces a continuous piecewise linear density estimate. We demonstrate the performance of these two improvements using simulated and real date examples.

14.
J Diabetes Res ; 2016: 4596316, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27239479

RESUMO

One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF.


Assuntos
Glicemia/metabolismo , Líquido Extracelular/metabolismo , Animais , Automonitorização da Glicemia , Simulação por Computador , Glucose/metabolismo , Camundongos , Microcirculação , Modelos Teóricos , Ratos
16.
Genes Cancer ; 6(9-10): 371-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26622940

RESUMO

WWP2 is a ubiquitin E3 ligase belonging to the Nedd4-like family. Given that WWP2 target proteins including PTEN that are crucial for regulating cell proliferation or suppressing tumorigenesis, we have asked whether WWP2 plays a role in controlling cell cycle progression. Here we report that WWP2 is necessary for normal cell cycle progression as its silencing significantly reduces the cell proliferation rate. We have identified that an isoform of WWP2 (WWP2-V4) is highly expressed in the M phase of the cell cycle. Silencing of WWP2 accelerates the turnover of cyclin E, which is accompanied by increased levels of phospho-histone H3 (p-H3) and cyclin B. Moreover, silencing of WWP2 results in compromised phosphorylation of Akt(S473), a residue whose phosphorylation is tightly associated with the activation of the kinase. Combined, these results strongly suggest that WWP2 is an important component in regulating the Akt signaling cascade, as well as cell cycle progression.

17.
Physiol Rep ; 2(7)2014 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-25347850

RESUMO

Our previous finding of a fractal pattern for gastric pH and esophageal pH plus the statistical association of sequential pH values for up to 2 h led to our hypothesis that the fractal pattern encodes information regarding gastric acidity and that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity by influencing gastric secretion of acid or bicarbonate. Under our hypothesis values of gastric pH should provide information regarding values of esophageal pH and vice versa. We used vector autoregression, a theory-free set of inter-related linear regressions used to measure relationships that can change over time, to analyze data from 24-h recordings of gastric pH and esophageal pH. We found that in pH records from normal subjects, as well as from subjects with gastroesophageal reflux disease alone and after treatment with a proton pump inhibitor, gastric pH values provided important information regarding subsequent values of esophageal pH and values of esophageal pH provided important information regarding subsequent values of gastric pH. The ability of gastric pH and esophageal pH to provide information regarding subsequent values of each other was reduced in subjects with gastroesophageal reflux disease compared to normal subjects. Our findings are consistent with the hypothesis that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity, and that this ability is impaired in subjects with gastroesophageal reflux disease.

18.
J Biol Chem ; 289(43): 29827-35, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25202016

RESUMO

Increased concentrations of extracellular solutes affect cell function and fate by stimulating cellular responses, such as evoking MAPK cascades, altering cell cycle progression, and causing apoptosis. Our study results here demonstrate that hyperosmotic stress induced H2AX phosphorylation (γH2AX) by an unrevealed kinase cascade involving polo-like kinase 3 (Plk3) in human corneal epithelial (HCE) cells. We found that hyperosmotic stress induced DNA-double strand breaks and increased γH2AX in HCE cells. Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3. Plk3 directly interacted with H2AX and was colocalized with γH2AX in the nuclei of hyperosmotic stress-induced cells. Suppression of Plk3 activity by overexpression of a kinase-silencing mutant or by knocking down Plk3 mRNA effectively reduced γH2AX in hyperosmotic stress-induced cells. This was consistent with results that show γH2AX was markedly suppressed in the Plk3(-/-) knock-out mouse corneal epithelial layer in response to hyperosmotic stimulation. The effect of hyperosmotic stress-activated Plk3 and increased γH2AX in cell cycle progression showed an accumulation of G2/M phase, altered population in G1 and S phases, and increased apoptosis. Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited γH2AX. This Plk3-mediated activation of γH2AX subsequently regulates the cell cycle progression and cell fate.


Assuntos
Ciclo Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Epitélio Anterior/citologia , Histonas/metabolismo , Pressão Osmótica , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Quebras de DNA de Cadeia Dupla , Embrião de Mamíferos/citologia , Fibroblastos/metabolismo , Humanos , Camundongos Knockout , Fosforilação , Ligação Proteica
19.
J Occup Health Psychol ; 18(4): 406-416, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24099160

RESUMO

The aim of this study was twofold: first, to delineate the underlying motives of the act of presenteeism and develop suitable measures for both the motives and the behavioral manifestation of the act; second, to systematically examine work and health consequences of the act of presenteeism in a Chinese work context. Using structured questionnaires, we employed a 2-wave panel study design in which antecedents, motives, and consequences of the act of presenteeism were measured in a diverse sample of 245 full-time Chinese employees in Taiwan. Hierarchical regression analyses showed that self-efficacy and neuroticism were significantly associated with approach and avoidance motives for the act of presenteeism, respectively. Moreover, analyzing the panel data with fixed effects specifications, we found that the act of presenteeism was negatively associated with employees' physical health, mental health, and job satisfaction, whereas it was positively associated with exhaustion. In conclusion, the present study shed some light on motives, behavioral manifestations, antecedents, and consequences of the act of presenteeism to extend the existing literature.


Assuntos
Absenteísmo , Emprego/psicologia , Motivação , Transtornos de Ansiedade/psicologia , Feminino , Nível de Saúde , Humanos , Satisfação no Emprego , Masculino , Neuroticismo , Determinação da Personalidade , Autoeficácia , Inquéritos e Questionários , Taiwan/epidemiologia
20.
Chem Sci ; 4(10): 3986-3996, 2013 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-24163730

RESUMO

Photosystem II supports four manganese centers through nine oxidation states from manganese(II) during assembly through to the most oxidized state before O2 formation and release. The protein-based carboxylate and imidazole ligands allow for significant changes of the coordination environment during the incorporation of hydroxido and oxido ligands upon oxidation of the metal centers. We report the synthesis and characterization of a series of tetramanganese complexes in four of the six oxidation states from MnII3MnIII to MnIII2 MnIV2 with the same ligand framework (L) by incorporating four oxido ligands. A 1,3,5-triarylbenzene framework appended with six pyridyl and three alkoxy groups was utilized along with three acetate anions to access tetramanganese complexes, Mn4O x , with x = 1, 2, 3, and 4. Alongside two previously reported complexes, four new clusters in various states were isolated and characterized by crystallography, and four were observed electrochemically, thus accessing the eight oxidation states from MnII4 to MnIIIMnIV3. This structurally related series of compounds was characterized by EXAFS, XANES, EPR, magnetism, and cyclic voltammetry. Similar to the ligands in the active site of the protein, the ancillary ligand (L) is preserved throughout the series and changes its binding mode between the low and high oxido-content clusters. Implications for the rational assembly and properties of high oxidation state metal-oxido clusters are presented.

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