MicroRNA‐140‐5p (miRNA‐140‐5p) is important for embryonic bone development. In this study, we found that miRNA‐140‐5p and its binding site in the 3′UTR of bone morphogenetic protein 2 (BMP‐2) are highly conserved among vertebrates, and miRNA‐140‐5p negatively regulates both zebrafish and human BMP‐2 genes. Microinjection of miRNA‐140‐5p or BMP‐2b morpholino into zebrafish embryos led to a similar phenotype, including shortened tails, curved trunks, and defects in cranial cartilage. Moreover, miRNA‐140‐5p injection induced zebrafish embryo malformation that could be significantly rescued by microinjection of BMP‐2 mRNA. In conclusion, our results indicated that miRNA‐140‐5p regulates zebrafish embryonic bone development via targeting BMP‐2.

Purpose Oxymatrine, an alkaloid extracted from the Chinese herb Sophora flavescens Aiton, possesses anti-inflammatory, anti-immune, anti-hepatic fibrosis, and anti-cancer properties. However, the effects of oxymatrine on epithelial-mesenchymal transition (EMT) of breast cancer cells are still unclear. Aim The present study was performed to investigate whether oxymatrine reverses EMT in breast cancer cells and to explore the underlying molecular mechanisms. Materials and methods MTT assay was performed to evaluate cell viability. Wound-healing assay and transwell chamber assay were used to assess cell migration and invasion, respectively. Immunofluorescence and Western blot were used to study the expression of EMT-related molecules and α Ⅴ β 3 integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of α Ⅴ β 3 integrin, was used to stimulate α Ⅴ β 3 integrin signaling. Results Our results demonstrated that oxymatrine effectively suppressed the viability of MDA-MB-231 and 4T1 breast cancer cells, and oxymatrine showed less cytotoxicity on normal breast mammary epithelial MCF-10A cells. In addition, oxymatrine reversed EMT in the MDA-MB-231 and 4T1 cells at nontoxic concentrations. Oxymatrine significantly inhibited cell migration and invasion, downregulated the expression of N-cadherin, vimentin, and Snail in MDA-MB-231 and 4T1 cells, but upregulated the expression of E-cadherin in 4T1 cells. The mechanism revealed that oxymatrine decreased the expression of α Ⅴ and β 3 integrin and their co-localization. It also inhibited α Ⅴ β 3 integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and α Ⅴ β 3 integrin/FAK/PI3K/Akt signaling activation. Conclusion Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing α Ⅴ β 3 integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.

The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions.

Diabetic cardiomyopathy (DCM) is the principal cause of death in people with diabetes. However, there is currently no effective strategy to prevent the development of DCM. Although cyclovirobuxine D (CVB-D) has been widely used to treat multiple cardiovascular diseases, the possible beneficial effects of CVB-D on DCM remained unknown. The present aim was to explore the potential effects and underlying mechanisms of CVB-D on DCM. We explored the effects of CVB-D in DCM by using high fat high sucrose diet and streptozotocin-induced rat DCM model. Cardiac function and survival in rats with DCM were improved via the amelioration of oxidative damage after CVB-D treatment. Our data also demonstrated that pre-treatment with CVB-D exerted a remarkable cytoprotective effect against high glucose-or H 2 o 2-induced neonatal rat cardiomyocyte damage via the suppression of reactive oxygen species accumulation and restoration of mitochondrial membrane potential; this effect was associated with promotion of Nrf2 nuclear translocation and its downstream antioxidative stress signals (NQO-1, Prdx1). Overall, the present data has provided the first evidence that CVB-D has potential therapeutic in DCM, mainly by activation of the Nrf2 signalling pathway to suppress oxidative stress. Our findings also have positive implications on the novel promising clinical applications of CVB-D. Diabetic cardiomyopathy (DCM) is usually characterised by cardiac structure and functional disorders in individuals with diabetes independent of hypertension or ischemic coronary artery disease 1-3. Although it is the principal cause of death in patients with diabetes, no effective strategies currently exist to prevent the progression of DCM 4. The pathogenesis of DCM involves in many factors such as oxidative stress, chronic low-grade inflammation 5 , autophagy 6 , and pyroptosis 7 , etc. The accumulated evidences confirm that cardiomyocyte injuries induced by oxidative stress are the predominant contributors to the pathophysiological process of DCM 8. Reactive oxygen species (ROS) overproduction induced by hyperglycaemia, free fatty acids, and glycosylation end products results in myocardial structural damage and functional or metabolic disorders, which are considered to be the key pathological signal of DCM 9. Therefore, amelioration of oxidative stress may be a therapeutic strategy to prevent the progression of DCM. Nuclear factor (carotenoid-derived 2)-like 2 (Nrf2) is the major transcription factor in the cellular antioxidant response 10. The expression and activity of Nrf2 are regulated by cullin 3-based ubiquitin E3 ligases, such as Kelch-like ECH-related protein 1 (Keap1). Upon exposure to various stress conditions, Nrf2 is uncoupled from

An AIE fluorescent supramolecular polymer (TPE-B@Q[10]) has been constructed from the newly synthesized AIE molecule TPE-B and the cucurbituril Q[10] via host-guest interactions. The molar ratio of Q[10]:TPE-B was found...