Pitavastatin ameliorates myocardial injury by inhibiting myocardial inflammation and oxidative stress by modulating the microRNA-106B-5p/mitogen-activated protein kinase kinase kinase 2 axis.

Myocarditis (MC) is a myocardial inflammatory disease that threats human life. Pitavastatin (Pit) is a unique lipophilic statin with potent effects on lowering plasma total cholesterol and triacylglycerols. It has been reported to have pleiotropic effects, such as reducing inflammation and oxidative stress. However, the regulatory mechanism of Pit in MC remains a mystery. Two MC models were established in vitro (lipopolysaccharides-(LPS)-stimulated H9c2 cells) and in vivo (intraperitoneal injection of LPS in mice). The levels of microRNA-106b-5p (miR-106b-5p) and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) were detected. ELISA was used to analyze in vivo cell inflammatory factors and myocardial injury markers, kits were used to detect the expression of antioxidant enzymes, cell counting kit-8 (CCK-8) was used to detect cell proliferation, and flow cytometry was used to detect apoptosis. Hematoxylin and eosin (HE) staining was used to detect the pathological changes of myocardial tissue in mice, and TUNEL staining was used to detect in vivo tissue cell apoptosis. The regulatory mechanism of Pit on miR-106b-5p/MAP3K2 was verified by a series of functional rescue experiments. The results demonstrated that in LPS-induced H9c2 cells, antioxidant enzymes decreased and pro-inflammatory factors and cardiac injury markers increased (p<0.05). However, these phenomenons were attenuated by Pit pretreatment. LPS decreased miR-106b-5p and elevated MAP3K2 in H9c2 cells, while Pit could recover their expression patterns (p<0.05). MAP3K2 was confirmed as a target gene of miR-106b-5p. Upregulating miR-106b-5p or downregulating MAP3K2 could further promote the protective effect of Pit, and vice versa (p<0.05). In addition, in the LPS-induced MC mouse model, histological examination showed that Pit significantly improved the myocardial tissue damage in MC mice, while downregulating miR-106b-5p or upregulating MAP3K2 could suppress the ameliorative effect of Pit (p<0.05). In conclusion, our study demonstrated that Pit ameliorates myocardial injury by suppressing myocardial inflammation and oxidative stress by modulating the miR-106b-5p/MAP3K2 axis.

MiR-15a-3p suppresses the growth and metastasis of ovarian cancer cell by targeting Twist1.

OBJECTIVE: To investigate the roles of miR-15a-3p in ovarian cancer cell growth and metastasis. PATIENTS AND METHODS: A key role of miR-15a-3p was identified via gene profiling and bioinformatics analysis. The impact of miR-15a-3p on ovarian cancer cell growth, migration and invasion was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), wound-healing and transwell invasion assays. Bioinformatics and luciferase reporter assays were applied to identify that twist family BHLH transcription factor 1 (Twist1) was the target gene of miR-15a-3p. The miR-15a-3p level and the expression of Twist1 were detected using quantitative Real-time polymerase chain reaction (qRT-PCR) assay. The expressions of N-cadherin and E-cadherin were measured by immunofluorescence staining. Small interfering RNA targeting Twist1 and pCDNA3.1 containing Twist1 were applied to decrease and increase the expression of Twist1, respectively. RESULTS: miR-15a-3p was markedly down-regulated in ovarian cancer. Exogenous up-regulation of miR-15a-3p inhibited the growth, colony formation, migration and invasion of ovarian cancer cell in vitro. Furthermore, a xenograft model indicated that miR-15a-3p inhibited tumour growth and the metastatic potential of ovarian cancer cell in vivo. We found that Twist1 was the direct target of miR-15a-3p in ovarian cancer and that its expression was negatively correlated with the level of miR-15a-3p in ovarian cancer tissues. Up-regulation of miR-15a-3p rescued the inhibitory impact of miR-15a-3p on ovarian cancer cell growth, migration and invasion. Finally, down-regulation of Twist1 mimicked the suppressive effects of miR-15a-3p on ovarian cancer cell. CONCLUSIONS: We demonstrated that miR-15a-3p is down-regulated in ovarian cancer. Up-regulation of miR-15a-3p restrains the growth and metastasis of ovarian cancer cell by regulating Twist1.

Aerosol synthesis of phase-controlled iron-graphene nanohybrids through FeOOH nanorod intermediates.

Iron-based nanoparticles form the basis for a host of sustainable alternative technologies based on this earth-abundant, low-toxicity element that can adopt a variety of oxidation states, crystal phases, and functions. Control of size, shape, and phase stability is a challenge for many nano-iron-based technologies, especially those involving Fe0 that is susceptible to oxidation under ambient conditions. This article presents a continuous method for hybridizing Fe-based nanoparticles with carbon in the form of graphene-encapsulated Fe-based particles with core-shell symmetry that allows flexible control of iron particle size, shape, and phase stability. The method uses FeOOH nanorods and graphene oxide as precursors, and subjects them to an aerosol-phase microdroplet drying and annealing process to yield a range of Fe/C nanohybrids whose structure can be controlled through adjustment of aerosol process temperature and post-synthesis thermal treatment conditions. We demonstrate that FeOOH nanorods can be successfully encapsulated in graphene, and transform during annealing into encapsulated Fe3O4 or Fe0 nanoparticles by reductive fragmentation, where the graphene nanosack acts as a carbothermic reductant. The hybrids are characterized by vibrating sample magnetometry and Cr(VI) reduction rates in aqueous media. The Fe0-graphene hybrids show high activity, good stability, and good recyclability in aqueous Cr(VI) removal due to the effect of graphene encapsulation. The present work suggests this rapid and continuous synthesis method can produce stable Fe-based materials, and can be extended to other metal systems, where graphene encapsulation can induce in situ reduction of metal oxide precursors into zero-valent metal-graphene hybrids.