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1.
Toxicol Res ; 39(4): 711-719, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37779582

RESUMO

The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated ß-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our findings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.

2.
Toxicol Res ; 38(4): 591-600, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36277372

RESUMO

2,4,3',5'-Tetramethoxystilbene (TMS) is a selective inhibitor of cytochrome P450 1B1 to block the conversion from estradiol to 4-OH-estradiol. Several studies suggested that TMS may act as a potent anti-cancer agent for hormone-related cancer including cervical cancer. Nutlin-3a is a cis-imidazoline analog that interferes with the interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53. The purpose of the study was to compare the cytotoxic effect of TMS and nutlin-3a treatment individually and in combination in HeLa cells. To assess the potential synergistic effects between TMS and nutlin-3a, low concentrations of TMS and nutlin-3a were simultaneously treated in HeLa cells. Based on cell viability, apoptosis assays, and the increase in cleaved caspase-3 and poly (ADP-ribose) polymerase cleavage, it was demonstrated that the combination with TMS and nutlin-3a exerts a synergistic effect on cancer cell death. Isobologram analysis of HeLa cells noted synergism between TMS and nutlin-3a. The combined treatment increased the expression of mitochondrial pro-apoptotic factors such as Bax and Bak, and decreased the expression of the XIAP. In addition, combination treatment significantly enhanced the translocation of AIF to the nucleus in HeLa cells. In conclusion, the results demonstrate that the combination of TMS and nutlin-3a induces synergistic apoptosis in HeLa cells, suggesting the possibility that this combination can be applied as a novel therapeutic strategy for cervical cancer.

3.
Polymers (Basel) ; 13(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923627

RESUMO

With the development of microelectronic devices having miniaturized and integrated electronic components, an efficient thermal management system with lightweight materials, which have outstanding thermal conductivity and processability, is becoming increasingly important. Recently, the use of polymer-based thermal management systems has attracted much interest due to the intrinsic excellent properties of the polymer, such as the high flexibility, low cost, electrical insulation, and excellent processability. However, most polymers possess low thermal conductivity, which limits the thermal management applications of them. To address the low thermal conduction of the polymer materials, many kinds of thermally conductive fillers have been studied, and the carbon-based polymer composite is regarded as one of the most promising materials for the thermal management of the electric and electronic devices. In addition, the next generation electronic devices require composite materials with various additional functions such as flexibility, low density, electrical insulation, and oriented heat conduction, as well as ultrahigh thermal conductivity. In this review, we introduce the latest papers on thermally conductive polymer composites based on carbon fillers with sophisticated structures to meet the above requirements. The topic of this review paper consists of the following four contents. First, we introduce the design of a continuous three-dimensional network structure of carbon fillers to reduce the thermal resistance between the filler-matrix interface and individual filler particles. Second, we discuss various methods of suppressing the electrical conductivity of carbon fillers in order to manufacture the polymer composites that meet both the electrical insulation and thermal conductivity. Third, we describe a strategy for the vertical alignment of carbon fillers to improve the through-plane thermal conductivity of the polymer composite. Finally, we briefly mention the durability of the thermal conductivity performance of the carbon-based composites. This review presents key technologies for a thermal management system of next-generation electronic devices.

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