Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
The antiferroelectricity in HfZrO 2 (HZO) annealed at 600 °C with an abrupt turn ON of FET characteristics with SSmin = 23 mV/dec and SSavg = 50 mV/dec over 4 decades of IDS is demonstrated. The near ...non-hysteresis is achieved with an antiferroelectric-like HZO due to a small remanent polarization and a coercive field. A feasible concept of coupling the antiferroelectric and ferroelectric type HZO are used for low-power electronics and the memory applications, respectively.
Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, ...represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
IMPACT OF TYPHOONS ON THE OCEAN IN THE PACIFIC D’Asaro, E.A.; Black, P. G.; Centurioni, L. R. ...
Bulletin of the American Meteorological Society,
09/2014, Letnik:
95, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Tropical cyclones (TCs) change the ocean by mixing deeper water into the surface layers, by the direct air–sea exchange of moisture and heat from the sea surface, and by inducing currents, surface ...waves, and waves internal to the ocean. In turn, the changed ocean influences the intensity of the TC, primarily through the action of surface waves and of cooler surface temperatures that modify the air–sea fluxes. The Impact of Typhoons on the Ocean in the Pacific (ITOP) program made detailed measurements of three different TCs (i.e., typhoons) and their interaction with the ocean in the western Pacific. ITOP coordinated meteorological and oceanic observations from aircraft and satellites with deployments of autonomous oceanographic instruments from the aircraft and from ships. These platforms and instruments measured typhoon intensity and structure, the underlying ocean structure, and the long-term recovery of the ocean from the storms' effects with a particular emphasis on the cooling of the ocean beneath the storm and the resulting cold wake. Initial results show how different TCs create very different wakes, whose strength and properties depend most heavily on the nondimensional storm speed. The degree to which air–sea fluxes in the TC core were reduced by ocean cooling varied greatly. A warm layer formed over and capped the cold wakes within a few days, but a residual cold subsurface layer persisted for 10–30 days.
Layered deformation in the Taiwan orogen Huang, T.-Y.; Gung, Y.; Kuo, B.-Y. ...
Science (American Association for the Advancement of Science),
08/2015, Letnik:
349, Številka:
6249
Journal Article
Recenzirano
The underthrusting of continental crust during mountain building is an issue of debate for orogens at convergent continental margins. We report three-dimensional seismic anisotropic tomography of ...Taiwan that shows a nearly 90° rotation of anisotropic fabrics across a 10- to 20-kilometer depth, consistent with the presence of two layers of deformation. The upper crust is dominated by collision-related compressional deformation, whereas the lower crust of Taiwan, mostly the crust of the subducted Eurasian plate, is dominated by convergence-parallel shear deformation. We interpret this lower crustal shearing as driven by the continuous sinking of the Eurasian mantle lithosphere when the surface of the subducted plate is coupled with the orogen. The two-layer deformation clearly defines the role of subduction in the formation of the Taiwan mountain belt.
Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose ...was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han‐Chinese patients without prior warfarin treatments. Using the genotype‐based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics‐based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.
Clinical Pharmacology & Therapeutics (2008); 84, 1, 83–89 doi:10.1038/sj.clpt.6100453
Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with ...vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor-binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma. Enforced expression of IGFBP2 increased network formation of glioma cells in vitro by activating CD144 and MMP2 (Matrix Metalloproteinase 2). U251 cells with stable knockdown of IGFBP2 led to decreased VM formation and tumor progression in orthotopic mouse model. Mechanistically, IGFBP2 interacts with integrin α5 and β1 subunits and augments CD144 expression in a FAK/ERK pathway-dependent manner. Luciferase reporter and ChIP assay suggested that IGFBP2 activated the transcription factor SP1, which could bind to CD144 promoter. Thus, IGFBP2 acts as a stimulator of VM formation in glioma cells via enhancing CD144 and MMP2 expression.
Purpose
In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of ...delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications.
Methods
We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort.
Results
A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%,
p
= 1.00) and major complications (2.5% vs. 6.2%,
p
= 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications.
Conclusion
Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.
The migration of Neptune's resonances through the proto-Kuiper Belt has been imprinted in the distribution of small bodies in the outer solar system. Here we analyze five published Neptune migration ...models in detail, focusing on the high pericenter distance (high-q) trans-Neptunian objects (TNOs) near Neptune's 5:2 and 3:1 mean-motion resonances because they have large resonant populations, are outside the main classical belt, and are relatively isolated from other strong resonances. We compare the observationally biased output from these dynamical models with the detected TNOs from the Outer Solar System Origins Survey (OSSOS) via its Survey Simulator. All four of the new OSSOS detections of high-q nonresonant TNOs are on the sunward side of the 5:2 and 3:1 resonances. We show that even after accounting for observation biases, this asymmetric distribution cannot be drawn from a uniform distribution of TNOs at 2 confidence. As shown by previous work, our analysis here tentatively confirms that the dynamical model that uses grainy slow Neptune migration provides the best match to the real high-q TNO orbital data. However, due to extreme observational biases, we have very few high-q TNO discoveries with which to statistically constrain the models. Thus, this analysis provides a framework for future comparison between the output from detailed, dynamically classified Neptune migration simulations and the TNO discoveries from future well-characterized surveys. We show that a deeper survey (to a limiting r-magnitude of 26.0) with a similar survey area to OSSOS could statistically distinguish between these five Neptune migration models.
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