All-Trans-Retinoic Acid Suppresses Neointimal Hyperplasia and Inhibits Vascular Smooth Muscle Cell Proliferation and Migration via Activation of AMPK Signaling Pathway

The proliferation and migration of vascular smooth muscle cells (VSMC) is extensively involved in pathogenesis of neointimal hyperplasia. All-trans-retinoic acid (ATRA) is a natural metabolite of vitamin A. Here, we investigated the involvement of AMP-activated protein kinase (AMPK) in the anti-neointimal hyperplasia effects of ATRA. We found that treatment with ATRA significantly reduced neointimal hyperplasia in the left common carotid artery ligation mouse model. ATRA reduced the proliferation and migration of VSMC, A7r5 and HASMC cell lines. Our results also demonstrated that ATRA altered the expression of proliferation-related proteins, including CyclinD1, CyclinD3, CyclinA2, CDK2, CDK4, and CDK6 in VSMC. ATRA dose-dependently enhanced the phosphorylation level of AMPKα (Thr172) in the left common carotid artery of experimental mice. Also, the phosphorylation level of AMPKα in A7r5 and HASMC was significantly increased. In addition, ATRA dose-dependently reduced the phosphorylation levels of mTOR and mTOR target proteins p70 S6 kinase (p70S6K) and 4E-binding protein 1 (4EBP1) in A7r5 and HASMC. Notably, the inhibition of AMPKα by AMPK inhibitor (compound C) negated the protective effect of ATRA on VSMC proliferation in A7r5. Also, knockdown of AMPKα by siRNA partly abolished the anti-proliferative and anti-migratory effects of ATRA in HASMC. Molecular docking analysis showed that ATRA could dock to the agonist binding site of AMPK, and the binding energy between AMPK and ATRA was -7.91 kcal/mol. Molecular dynamics simulations showed that the binding of AMPK-ATRA was stable. These data demonstrated that ATRA might inhibit neointimal hyperplasia and suppress VSMC proliferation and migration by direct activation of AMPK and inhibition of mTOR signaling

The Influence of Distinct Seasons on the Succession and Diversity of Bacteria on the Anticorrosive Coatings Surfaces in a Marine Environment

Epoxy resin has been frequently used as a coating paint for anticorrosion protection because of its excellent chemical properties. However, the long-term succession of bacteria colonizing coatings surfaces in the different seasons of the year remains uncharacterized. In this work, amplicon-based 16s rDNA sequencing was used to characterize the tempol change of bacterial communities growing on the epoxy resin surfaces. The results showed that bacterial diversity indices on spring and autumn immersion samples were higher than that of the samples immersed on summer and winter samples. Proteobacteria was found to be the dominant bacteria of all different seasons and accounted for 57.9% of the total sequence. Gammaproteobacteria and Alphaproteobacteria were the dominant classes in all of the samples, whereas the most abundance bacteria at the genus level had the significant differences with a change of season. Firmicutes also displayed a distinct temporal change pattern in that it was the second abundance in the summer and autumn samples, but had a marked decrease in the other season samples. These results demonstrated that bacterial community composition underwent obvious changes over the distinct seasons of a year. This study will be helpful for the seasonal change of bacterial diversity and development of corrosion-resistant paints

The Role of ZNF275/AKT Pathway in Carcinogenesis and Cisplatin Chemosensitivity of Cervical Cancer Using Patient-Derived Xenograft Models

Zinc finger protein 275 (ZNF275) is a C2H2-type transcription factor that is localized on chromosome Xq28. Whether ZNF275 participates in modulating the biological behaviors of cervical cancer has not been determined to our knowledge. The present study employed CCK-8, BrdU, flow cytometry, and a transwell assay to investigate the cell viability, proliferation, apoptosis, migration, and invasion of cervical cancer cells. The application of Western blotting and immunohistochemistry (IHC) aims to assess ZNF275 protein expression and identify the signaling pathway relevant to ZNF275-mediated effects on cervical cancer. The therapeutic impact of the combined therapy of the AKT inhibitor triciribine and cisplatin was evaluated on cervical cancer patient-derived xenograft (PDX) models expressing high ZNF275. The current research illustrated that cervical cancer tissue exhibited a higher expression of ZNF275 in contrast to the surrounding normal cervical tissue. The downregulation of ZNF275 suppressed cell viability, migration, and invasion, and facilitated the apoptosis of SiHa and HeLa cells via weakening AKT/Bcl-2 signaling pathway. Moreover, triciribine synergized with cisplatin to reduce cell proliferation, migration, and invasion, and enhanced the apoptosis of SiHa cells expressing high ZNF275. In addition, the combination treatment of triciribine and cisplatin was more effective in inducing tumor regression than single agents in cervical cancer PDX models expressing high ZNF275. Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results

The Influence of Distinct Seasons on the Succession and Diversity of Bacteria on the Anticorrosive Coatings Surfaces in a Marine Environment

Epoxy resin has been frequently used as a coating paint for anticorrosion protection because of its excellent chemical properties. However, the long-term succession of bacteria colonizing coatings surfaces in the different seasons of the year remains uncharacterized. In this work, amplicon-based 16s rDNA sequencing was used to characterize the tempol change of bacterial communities growing on the epoxy resin surfaces. The results showed that bacterial diversity indices on spring and autumn immersion samples were higher than that of the samples immersed on summer and winter samples. Proteobacteria was found to be the dominant bacteria of all different seasons and accounted for 57.9% of the total sequence. Gammaproteobacteria and Alphaproteobacteria were the dominant classes in all of the samples, whereas the most abundance bacteria at the genus level had the significant differences with a change of season. Firmicutes also displayed a distinct temporal change pattern in that it was the second abundance in the summer and autumn samples, but had a marked decrease in the other season samples. These results demonstrated that bacterial community composition underwent obvious changes over the distinct seasons of a year. This study will be helpful for the seasonal change of bacterial diversity and development of corrosion-resistant paints