Cardiac hypertrophy is one of the major risk factors of cardiovascular morbidity and mortality. Autophagy is acknowledged to be an important mechanism regulating cardiac hypertrophy. Sestrin 1, a downstream target gene of p53, has been proven to regulate autophagy. However, the role of Sestrin 1 in cardiac hypertrophy remains unknown. Our study showed that Sestrin 1 mRNA and protein expression declined in pressure overload cardiac hypertrophy and phenylephrine (PE)‐induced cardiac hypertrophy. Knockdown of Sestrin 1 by RNAi deteriorated PE‐induced cardiac hypertrophy, whereas the overexpression of Sestrin 1 by adenovirus transfection blunted hypertrophy. We discovered that knockdown of Sestrin 1 resulted in impaired autophagy while overexpression of Sestrin 1 resulted in increased autophagy without affecting lysosomal function. In addition, the antihypertrophic effect of Sestrin 1 overexpression was eliminated by autophagy blockade. Importantly, Sestrin 1 targets at the AMPK/mTORC1/autophagy pathway to inhibit cardiac hypertrophy by interaction with AMPK which is responsible for autophagy regulation. Taken together, our data indicate that Sestrin 1 regulates AMPK/mTORC1/autophagy axis to attenuate cardiac hypertrophy.
The chemoresistance of 5-fluorouracil (5-FU) limited the application of chemotherapy in colorectal cancer (CRC) treatment. Herein, we aimed to uncover the potential mechanism behind the 5-FU resistance of CRC cells. Methods: The abundance of long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1), microRNA-23b-3p (miR-23b-3p) and zinc finger protein 281 (ZNF281) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. Western blot was conducted to examine autophagy-related proteins, apoptosisassociated proteins and ZNF281 in CRC tissues and cells. Cell counting kit-8 (CCK8) assay was performed to detect the viability and inhibitory concentration 50% (IC50) value of 5-FU of CRC cells. The apoptosis of CRC cells was measured by flow cytometry. The binding sites between miR-23b-3p and UCA1 or ZNF281 were predicted by miRcode and Starbase software, respectively, and the combination was confirmed by dual-luciferase reporter assay and RIP assay. Murine xenograft model was established to verify the role of UCA1 on the 5-FU resistance of CRC in vivo. Results: The 5-FU resistance of CRC was positively related to the level of UCA1 and autophagy. UCA1 accelerated the 5-FU resistance of CRC cells through facilitating autophagy and suppressing apoptosis. MiR-23b-3p was a target of UCA1 in 293T and CRC cells. The knockdown of miR-23b-3p reversed the inhibitory effects of UCA1 interference on the 5-FU resistance and autophagy and the promoting impact on the apoptosis of CRC cells. ZNF281 could bind to miR-23b-3p in 293T cells. MiR-23b-3p elevated the 5-FU sensitivity through down-regulating ZNF281 in CRC cells. UCA1 interference enhanced the 5-FU sensitivity of CRC through miR-23b-3p/ZNF281 axis in vivo. Conclusion: UCA1 mediated 5-FU resistance of CRC cells through facilitating autophagy and inhibiting apoptosis via miR-23b-3p/ZNF281 axis in vivo and in vitro.
Gold nanotriangle (Au NT), a unique anisotropicshaped plasmonic nanostructure with distinctive optical, electrical, and catalytic characteristics, has been utilized in a variety of hightechnological applications. However, the basic and practical applications of Au NTs are often hindered by size and yield (less than 60%) and engineering a facile and manageable approach to acquire Au NTs with high yields is still challenging. Herein, a simple and rapid seed-mediated method to prepare high-purity Au NTs (up to 97.4%) is proposed by precisely controlling the reaction kinetics. Importantly, there are two key factors to achieve high-yield Au NTs (70%) during the two-growth synthesis: (1) the high concentration of hexadecyltrimethylammonium chloride (CTAC) that can provide a greater binding force on the ⟨111⟩ facet of Au seed and (2) the selective adsorption of potassium iodide (KI) on the ⟨111⟩ facet. Additionally, Au NTs with a wide range of sizes from 58 to 137 nm with a high uniformity can be tailored by a small window parameter regulation. Additionally, it is found that the addition of optimized salts can induce the rapid precipitation of Au NTs to form self-assembled microfibers and the efficient purification of Au NTs with a yield of about 97.4%. Furthermore, the finite difference time domain (FDTD) simulation shows that anisotropic electromagnetic field enhancements and hot spot excitation modes can be generated in different assembling models of Au NTs. Finally, we construct macroscopic two-dimensional (2D) ordered monolayer films of Au NTs through volatilizing self-assembly. As a proof of concept, the ordered Au NT arrays exhibit both high surface-enhanced Raman spectroscopy (SERS) sensitivity and detecting stability compared to random assembling structures and Au NPs. Therefore, we believe that our proposed rapid synthesis and high-yield purification approach of Au NTs would pave a way to prepare designed nanomaterials for a variety of basic and high-technological practical applications.
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