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1.
Biomed Pharmacother ; 170: 115982, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38056236

RESUMEN

The phosphatidyl inositol 3-kinase (PI3K)/AKT signaling plays a critical role in cancer cell proliferation, migration, and invasion. This signal transduction axis in HPV-positive cervical cancer has been proved to be directly activated by E6/E7 proteins of the virus enhancing cervical cancer progression. Hence, the PI3K/AKT pathway is one of the key therapeutic targets for HPV-positive cervical cancer. Here we discovered that oxyresveratrol (Oxy) at noncytotoxic concentration specifically suppressed the phosphorylation of AKT but not ERK1/2. This potent inhibitory effect of Oxy was still observed even when cells were stimulated with fetal bovine serum. Inhibition of AKT phosphorylation at serine 473 by Oxy resulted in a significant decrease in serine 9 phosphorylation of GSK-3ß, a downstream target of AKT. Dephosphorylation of GSK-3ß at this serine residue activates its function in promoting the degradation of MCL-1, an anti-apoptotic protein. Results clearly demonstrated that in association with GSK-3ß activation, Oxy preferentially downregulated the expression of anti-apoptotic protein MCL-1. Furthermore, results from the functional analyses revealed that Oxy inhibited cervical cancer cell proliferation, at least in part through suppressing nuclear expression of Ki-67. Besides, the compound retarded cervical cancer cell migration even the cells were exposed to a potent enhancer of epithelial-mesenchymal transition, TGF-ß1. In consistent with these data, Oxy reduced the expression of ß-catenin, N-cadherin, and vimentin. In conclusion, the study disclosed that Oxy specifically inhibits the AKT/GSK-3ß/MCL-1 axis resulting in reduction in cervical cancer cell viability, proliferation, and migration.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Transducción de Señal , beta Catenina/metabolismo , Serina/farmacología
2.
Artículo en Inglés | MEDLINE | ID: mdl-27547232

RESUMEN

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter and α2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, and α2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET and α2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels of α2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

3.
Saf Health Work ; 4(1): 37-45, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23516132

RESUMEN

OBJECTIVES: As quality of work-life (QWL) among nurses affects both patient care and institutional standards, assessment regarding QWL for the profession is important. Work-related Quality of Life Scale (WRQOLS) is a reliable QWL assessment tool for the nursing profession. To develop a Chinese version of the WRQOLS-2 and to examine its psychometric properties as an instrument to assess QWL for the nursing profession in China. METHODS: Forward and back translating procedures were used to develop the Chinese version of WRQOLS-2. Six nursing experts participated in content validity evaluation and 352 registered nurses (RNs) participated in the tests. After a two-week interval, 70 of the RNs were retested. Structural validity was examined by principal components analysis and the Cronbach's alphas calculated. The respective independent sample t-test and intra-class correlation coefficient were used to analyze known-group validity and test-retest reliability. RESULTS: One item was rephrased for adaptation to Chinese organizational cultures. The content validity index of the scale was 0.98. Principal components analysis resulted in a seven-factor model, accounting for 62% of total variance, with Cronbach's alphas for subscales ranging from 0.71 to 0.88. Known-group validity was established in the assessment results of the participants in permanent employment vs. contract employment (t = 2.895, p < 0.01). Good test-retest reliability was observed (r = 0.88, p < 0.01). CONCLUSION: The translated Chinese version of the WRQOLS-2 has sufficient validity and reliability so that it can be used to evaluate the QWL among nurses in mainland China.

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