Fused in sarcoma (FUS) inhibits milk production efficiency in mammals.

Efficient milk production in mammals confers evolutionary advantages by facilitating the transmission of energy from mother to offspring. However, the regulatory mechanism responsible for the gradual establishment of milk production efficiency in mammals, from marsupials to eutherians, remains elusive. Here, we find that mammary gland of the marsupial sugar glider contained milk components during adolescence, and that mammary gland development is less dynamically cyclic compared to that in placental mammals. Furthermore, fused in sarcoma (FUS) is found to be partially responsible for this establishment of low efficiency. In mouse model, FUS inhibit mammary epithelial cell differentiation through the cyclin-dependent kinase inhibitor p57Kip2, leading to lactation failure and pup starvation. Clinically, FUS levels are negatively correlated with milk production in lactating women. Overall, our results shed light on FUS as a negative regulator of milk production, providing a potential mechanism for the establishment of milk production from marsupial to eutherian mammals.

lncRNA SNHG17 promotes pancreatic carcinoma progression via cross-talking with miR-942.

OBJECTIVE: Long non-coding RNA (lncRNA) SNHG17 has been shown to modulate the biological behavior of multiple cancers (e.g., colorectal and lung cancers). However, its involvement in pancreatic cancer (PC) has not been explored; therefore, in the present study, we sought to examine this involvement. METHODS: First, the mRNA expression levels of various genes were quantified in PC tissues and cell lines using quantitative reverse-transcription PCR (qRT-PCR). The interaction between SNHG17 and miR-942 was explored by bioinformatics prediction as well as a dual luciferase reporter assay. The proliferation and viability of pancreatic carcinoma cells were examined using cell counting kit-8 and MTT assays, respectively. Cellular migratory and invasive properties were evaluated using transwell migration and wound healing assays. Cell death was measured using flow cytometry. Protein expression was quantified by western blotting. RESULTS: SNHG17 expression was markedly higher in human PC specimens and cell lines than in normal healthy tissues and pancreatic epithelial cells. MiR-942 expression displayed the opposite trend. Bioinformatics prediction and a dual luciferase reporter assay confirmed that SNHG17 serves as a sponge for miR-942. Loss-of-function assay revealed that SNHG17 silencing reduced the proliferation and viability of PC cells, impaired their migratory and invasive capacities, and led to their apoptosis. All these changes could be reversed by miR-942 inhibition. Further mechanical studies showed that SNHG17 silencing decreased the expression of several tumor modulators, including XXX, and this decrease was countered by miR-942 inhibition. CONCLUSION: Our study provides experimental evidence for an interaction between SNHG17 and miR-942, which may unveil a new approach for PC pharmacotherapy.

Protective effects of dioscin on vascular remodeling in pulmonary arterial hypertension via adjusting GRB2/ERK/PI3K-AKT signal.

Pulmonary arterial hypertension (PAH) is a progressive and lethal cardiopulmonary. Pulmonary vascular remodeling (PVR) caused by excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) is the chief pathological feature of PAH. Dioscin is a natural product that possesses multiple pharmacological activities, but its effect on PAH remains unclear. In this study, effect of dioscin on vascular remodeling in PAH was assessed in hypoxia-induced PASMCs, hypoxia-induced and monocrotaline (MCT)-induced rats. Western blot, Real-time PCR and siRNA transfection tests were applied to evaluate the possible mechanisms of dioscin. In vitro experiments, results showed dioscin markedly inhibited the proliferation and migration, and promoted apoptosis of hypoxic PASMCs. In vivo, dioscin significantly decreased the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI), and improved pulmonary vascular stenosis in rats induced by hypoxia or MCT. Molecular mechanism studies showed that dioscin significantly reduced the expression of growth factor receptor-bound protein 2 (GRB2). Subsequently, dioscin reduced the expressions of Ras, Cyclin D1, CDK4, c-Fos, PCNA and p-ERK to inhibit proliferation and migration of PASMCs, inhibited p-PI3K and p-AKT levels and increased Bax/Bcl2 ratio to promote cell apoptosis. GRB2 siRNA transfection in PASMCs further confirmed that the inhibitory action of dioscin in PAH was evoked by adjusting GRB2/ERK/PI3K-AKT signal. Taken together, our study indicated that dioscin attenuates PAH through adjusting GRB2/ERK/PI3K-AKT signal to inhibit PASMCs proliferation and migration, and promote apoptosis, and dioscin may be developed as a therapeutic strategy for treating PAH in the future.

Hepatoprotective Effect and Molecular Mechanisms of Hengshun Aromatic Vinegar on Non-Alcoholic Fatty Liver Disease.

Aromatic vinegar with abundant bioactive components can be used as a food additive to assist the treatment of various diseases. However, its effect on non-alcoholic fatty liver disease (NAFLD) is still unknown. The purpose of this study was to investigate the mechanism of Hengshun aromatic vinegar in preventing NAFLD in vivo and in vitro. Aromatic vinegar treatment was applied to rats fed with a high-fat diet (HFD) and HepG2 cells challenged with palmitic acid (PA). Our results showed that aromatic vinegar markedly improved cell viabilities and attenuated cell damage in vitro. The levels of TC, TG, FFA, AST, ALT, and malondialdehyde (MDA) in HFD-induced rats were significantly decreased by aromatic vinegar. Mechanism investigation revealed that aromatic vinegar markedly up-regulated the level of silent information regulator of transcription 1 (Sirt1), and thereby inhibited inflammation of the pathway through down-regulating the expressions of high mobility group box 1, toll-likereceptor-4, nuclear transcription factor-κB, tumor necrosis factor receptor-associated factor-6, and inflammatory factors. Aromatic vinegar simultaneously increased the expression of farnesoid X receptor and suppressed expressions of lipogenesis related proteins, including fatty acid synthase, acetyl-CoA carboxylase-1, sterol regulatory element binding transcription factor 1, and stearoyl-CoA desaturase-1. These results were further validated by knockdown of Sirt1 using siRNAs silencing in vitro. In conclusion, Hengshun aromatic vinegar showed protective effects against NAFLD by enhancing the activity of SIRT1 and thereby inhibiting lipogenesis and inflammation pathways, which is expected to become a new assistant strategy for NAFLD therapy in the future.