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1.
J Cell Mol Med ; 26(3): 789-799, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34953010

RESUMEN

The overall survival of glioblastoma multiforme (GBM) patients remains poor. To improve patient outcomes, effective diagnostic and prognostic biomarkers for GBM are needed. In this study, we first applied bioinformatic analyses to identify biomarkers for GBM, focusing on SOX (sex-determining region on the Y chromosome (SRY)-related high mobility group (HMG) box) B1 family members. The ONCOMINE, GEPIA, LinkedOmics and CCLE databases were used to assess mRNA expression levels of the SOX B1 family members in different cancers and normal tissue. Further bioinformatic analysis was performed using the ONCOMINE database in combination with the LinkedOmics data set to identify the prognostic value of SOX B1 family members for GBM. We found mRNA expression levels of all tested SOX B1 genes were significantly increased in GBM. In the LinkedOmics database, increased expression of SOX3 indicated a better overall survival. In GEPIA databases, increased expression of all SOX B1 family members suggested an improved overall survival, but none of them were statistically different. Then, Transwell assays and wound healing were employed to evaluate the motility and invasive captivity of U251 cells when silencing SOX2 and SOX3. We found exogenous inhibition of SOX2 appeared to reduce the migration and invasion of U251 cells in vitro. Collectively, our research suggested that SOX2 might serve as a cancer-promoting gene to identify high-risk GBM patients, and SOX3 had the potential to be a prognostic biomarker for GBM patients.


Asunto(s)
Glioblastoma , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos
3.
Front Mol Biosci ; 10: 1266243, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37808523

RESUMEN

Hypoxia induced by high altitude can lead to severe neurological dysfunction. Mitophagy is known to play a crucial role in hypoxic nerve injury. However, the regulatory mechanism of mitophagy during this injury remains unclear. Recent studies have highlighted the role of Sestrin2 (SESN2), an evolutionarily conserved stress-inducible protein against acute hypoxia. Our study demonstrated that hypoxia treatment increased SESN2 expression and activated mitophagy in PC12 cells. Furthermore, the knock-out of Sesn2 gene led to a significant increase in mitochondrial membrane potential and ATP concentrations, which protected the PC12 cells from hypoxic injury. Although the AMPK/mTOR pathway was significantly altered under hypoxia, it does not seem to participate in mitophagy regulation. Instead, our data suggest that the mitophagy receptor FUNDC1 plays a vital role in hypoxia-induced mitophagy. Moreover, SESN2 may function through synergistic regulation with other pathways, such as SESN2/AMPK, to mediate cellular adaptation to hypoxia, including the regulation of mitophagy in neuron cells. Therefore, SESN2 plays a critical role in regulating neural cell response to hypoxia. These findings offer valuable insights into the underlying molecular mechanisms governing the regulation of mitophagy under hypoxia and further highlight the potential of SESN2 as a promising therapeutic target for hypoxic nerve injury.

4.
Sci Rep ; 12(1): 12399, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35859040

RESUMEN

With the expansion of high-speed railway network in the world, it is inevitable for railways to pass through seasonal frozen regions. Since in a seasonal frozen region the ground can have significantly different mechanical properties between the freezing season and the warm season, train-induced ground vibration is also season-dependent but it has not received enough attention up to now. This paper gives an investigation into the effects of soil and fastener-freezing on ground vibrations induced by high-speed train in frozen regions. Based on the well-established relationships between soil mechanical properties and freezing temperature, a frozen ground is shown to be still represented by a layered ground and therefore, previously developed models for predicting ground vibration generated by a train running along a track resting on a layered ground can be readily applied. The effects of low temperature on the dynamical properties of fasteners are also considered. Results show that, due to the increased Young's modulus at freezing condition, the vibration level of a frozen ground near the track is lower than that of the non-frozen counterpart. However, well away from the track, the vibration level of the frozen ground is much stronger than that of the non-frozen one, mainly due to the much-reduced loss factor of the frozen ground, which results in slower attenuation of vibration with propagating distance. Results also show that, the difference in ground vibration between a frozen ground and its non-frozen counterpart is mainly caused by freezing of the ground. The emphasis of this study lies in making clear the characteristics of train-induced ground vibration in frozen regions and the differences between frozen and non-frozen regions, providing some new fundamental insights about this practical problem, which have significant engineering guidance and application value.

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