Acetate Upregulates GPR43 Expression and Function via PI3K-AKT-SP1 Signaling in Mammary Epithelial Cells during Milk Fat Synthesis.

This study investigated the mechanism underlying acetate-induced orphan G-protein-coupled receptor 43 (GPR43) expression and milk fat production. The mammary epithelial cells of dairy cows were treated with acetate, and the effects of GPR43 on acetate uptake and the expression of lipogenesis-related genes were determined by gas chromatography and quantitative polymerase chain reaction (qPCR), respectively. RNAi, inhibitor treatment, and luciferase assay were used to determine the effect of phosphoinositide 3-kinase-protein kinase B-specificity protein 1 (PI3K-AKT-SP1) signaling on acetate-induced GPR43 expression and function. The results showed that GPR43 was highly expressed in lactating cow mammary tissues, which was related to milk fat synthesis. 12 mM acetate significantly increased the GPR43 expression in mammary epithelial cells of dairy cows. In acetate-treated cells, GPR43 overexpression significantly increased the cellular uptake of acetate, the intracellular triacylglycerol (TAG) content, and acetate-induced lipogenesis gene expression. Acetate activated PI3K-AKT signaling and promoted SP1 translocation from the cytosol into the nucleus, where SP1 bound to the GPR43 promoter and upregulated GPR43 transcription. Moreover, the activation of PI3K-AKT-SP1 by acetate facilitated the trafficking of GPR43 from the cytosol to the plasma membrane. In conclusion, acetate upregulated GPR43 expression and function via PI3K-AKT-SP1 signaling in mammary epithelial cells, thereby increasing milk fat synthesis. These results provide an experimental strategy for improving milk lipid synthesis, which is important to the dairy industry.

Wanting to eat matters: Negative affect and emotional eating were associated with impaired memory suppression of food cues.

OBJECTIVE: Previous studies have linked emotional eating with negative affect and decreased inhibitory control. However, studies on inhibitory control have generally focused on motor inhibition. How to stop higher-level cognitive processes, such as food-related memory retrieval or voluntary thoughts, received few direct investigation in field of food intake or food-related decision making. The current study, adopting Anderson and Green's Think/No-Think paradigm, aimed to investigate the relationship between emotional eating, negative affect and food-related memory suppression. METHOD: Sixty-one young females participated in the current study, during which they finished food specific Think/No-Think task. Their positive and negative affect and eating style were measured using Positive Affect and Negative Affect Schedule and Dutch Eating Behavior Question. The reward value of the food item used in the Think/No-Think task was measured using liking and wanting ratings. RESULTS: As hypothesized, negative affect and emotional eating were associated with decreased memory suppression of palatable food cues. Further analysis showed that higher emotional eating was associated with greater wanting only among the food items which were previously suppressed however remembered later. DISCUSSION: The current study presents the first evidence that negative affect and emotional eating were associated with impaired memory suppression of palatable food cues, and it provided insight into the interaction between reward valuation for the food cues and hippocampal memory mechanisms during retrieval suppression.

Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer.

As a new member of Neks family, Nek9 regulates spindle assembly and controls chromosome alignment and centrosome separation. In the current study we aimed to investigate the expression of Nek9 in breast cancer and its clinical significance. We evaluated the expression of Nek9 in invasive ductal carcinoma (IDC, n=316), ductal carcinoma in situ (DCIS), usual ductal hyperplasia, atypical ductal hyperplasia, fibroadenoma and normal breast tissues using immunohistochemistry. The results revealed significantly reduced Nek9 in IDCs (41.8%) compared to benign breast lesions. Moreover, gradually reduced Nek9 was found from DCIS to invasive carcinoma and metastatic tumour within the same tumours. The decrease in Nek9 expression was associated with larger tumour size (p=0.0087), high grade (p<0.0001) and high Ki-67 index (p<0.0020). TCGA and GEO datasets analysis revealed low level of Nek9 mRNA was more frequent in triple negative breast cancers, and associated with poor overall survival and distant metastasis-free survival. These findings suggest an important role of Nek9 in the progression of breast cancer, and aberrantly expressed Nek9 correlates with more aggressive clinicopathological variables and predicts poor clinical prognosis. Nek9 may serve as a potential predictive factor for patients with breast cancer.

In Silico Analyses for Key Genes and Molecular Genetic Mechanism in Epilepsy and Alzheimer's Disease.

BACKGROUND: Epilepsy and Alzheimer's disease are common neuropathies with a complex pathogenesis. Both of them have some correlations in etiology, pathogenesis, pathological changes, clinical manifestations and treatment. OBJECTIVE: This study investigated the key genes and molecular genetic mechanism in epilepsy and Alzheimer's disease by bioinformatics analysis. METHOD: Two gene expression profiles were used to screen differentially expressed genes by GEO2R tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Then the protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software which can be used to analyze modules with MCODE. RESULTS: A total of 199 differentially expressed genes (DEGs) in the two groups. According to GO_BP analysis and KEGG pathway enrichment by DAVID, we found DEGs referring to several pathways significantly down-regulated in endocytosis, such as endocytosis, synaptic vesicle cycle, lysosome, cAMP signaling pathway, circadian entrainment, LTP, glutamatergic synapse and GABAergic synapse pathway. The regulator genes of the upstream pathway of circadian rhythms were obviously downgraded. CONCLUSION: Our research demonstrated that the regulatory genes of the upstream pathway of circadian rhythms were obviously downgraded. These biological pathways and DEGs or hub genes may contribute to revealing the molecular relationship between Alzheimer's disease and epilepsy.