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Most chemotherapeutic drugs are potent and have a very narrow range of dose safety and efficacy, most of which can cause many side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and serious side effect of chemotherapy for cancer treatment. However, its mechanism of action is yet to be fully elucidated. In the present study, we found that the treatment of the chemotherapy drug elemene induced hyperalgesia accompanied by anxiety-like emotions in mice based on several pain behavioral assays, such as mechanical allodynia and thermal hyperalgesia tests. Second, immunostaining for c-fos (a marker of activated neurons) further showed that elemene treatment activated several brain regions, including the lateral septum (LS), cingulate cortex (ACC), paraventricular nucleus of the thalamus (PVT), and dorsomedial hypothalamic nucleus (DMH), most notably in the GABAergic neurons of the lateral septum (LS). Finally, we found that both chemogenetic inhibition and apoptosis of LS neurons significantly reduced pain- and anxiety-like behaviors in mice treated with elemene. Taken together, these findings suggest that LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors, providing a new target for the treatment of chemotherapy pain induced by elemene. Graphical abstract A working model of chemotherapy drug induced pain accompanied by anxiety-like emotions in mice.Elemene can induce pain- and anxiety-like behaviors by activating GABAergic neurons in the LS, which can be alleviated by chemogenetic inhibition of GABAergic neurons in the LS. [Display omitted] • Elemene can induce pain- and anxiety-like behaviors by activating GABAergic neurons in the LS. • LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors. • Chemogenetic inhibition and apoptosis of LS neurons relieves elemene-induced pain- and anxiety-like behaviors. [ABSTRACT FROM AUTHOR]

Myo -inositol is a major intracellular osmolyte that can be accumulated to protect cells from a variety of stresses, including fluctuations in the osmolality of the environment, and cortisol is thought to be an osmotic hormone in teleost fish. In this study, dietary myo -inositol resulted in increased Na+-K+-ATPase activity and gene expression of partial ion channel genes and prolonged survival time of turbot (Scophthalmus maximus) under low salinity. The cortisol regulated by dietary myo -inositol also was correlated with these outcomes. The optimal concentrations of cortisol stimulated gill Na+-K+-ATPase activity and increased the expression of ion channel genes to enhance low salinity tolerance, as indicated by longer survival time under low salinity. When cortisol level was suppressed, myo -inositol failed to increase the survival time of turbot under low salinity, and strong correlations between cortisol concentration and Na+-K+-ATPase activity, expression of partial ion channel genes, and survival time of turbot were detected. These results showed that myo -inositol enhanced the low salinity tolerance of turbot by modulating cortisol synthesis. • The actions of myo -inositol on osmoregulation may be mediated by cortisol. • Cortisol plays an important role in osmotic regulation of turbot. • Cortisol may be an intermediate substance which inositol acts on osmoregulation. • myo -inositol enhances the low-salinity tolerance by modulating cortisol synthesis. [ABSTRACT FROM AUTHOR]

This study aims to explore the role of lncRNA MSC-AS1/microRNA-140–5p/BMP2 regulatory loop in promoting osteogenic differentiation of BMSCs. BMSCs were isolated from bone marrow of mice. Expression levels of MSC-AS1, microRNA-140–5p and BMP2 during osteogenic differentiation were detected by qRT-PCR. Meanwhile, regulatory effect of MSC-AS1 on osteogenic differentiation was detected through ALP staining and alizarin red staining. The binding sites between microRNA-140–5p and MSC-AS1 as well as between microRNA-140–5p and BMP2 were predicted by TargetScan, which were further confirmed by dual-luciferase reporter gene assay. In addition, protein levels of MSC-AS1/microRNA-140–5p/BMP2 were detected by Western blot. Finally, rescue experiments were conducted to clarify the regulatory effects of MSC-AS1/microRNA-140–5p/BMP2 axis on osteogenic differentiation. MSC-AS1 and BMP2 were found to be remarkably up-regulated during osteogenic differentiation, while microRNA-140–5p was conversely down-regulated. Meanwhile, knockdown of MSC-AS down-regulated expression levels of osteogenesis-associated genes and weakened the mineralization capacity of BMSCs. MicroRNA-140–5p was verified to bind to the 3′UTR of MSC-AS1 and BMP2 genes. Knockdown of MSC-AS1 in BMSCs could reduce the expression of microRNA-140–5p, while knockdown of microRNA-140–5p also down-regulated BMP2 level. In addition, co-silence of MSC-AS1 and microRNA-140–5p reversed the inhibitory effect of MSC-AS1 knockdown on osteogenic differentiation and protein levels of p-Smad1/5/8, RUNX2 and Osterix. MSC-AS1 might promote the osteogenic differentiation of BMSCs through sponging microRNA-140–5p to up-regulate BMP2, thus alleviating the progression of osteoporosis. • We first confirmed that the expression of MSC-AS1 was up-regulated during osteogenic differentiation. • MSC-AS1, as the ceRNA of microRNA-140-5p, regulated osteogenic differentiation of BMSCs via BMP2/Smad signaling. • MicroRNA-140-5p showed a time-dependent decrease during osteogenic differentiation. • The expression of microRNA-140-5p increased after MSC-AS1 was knocked down. [ABSTRACT FROM AUTHOR]