Orexin-A is a circulating neuropeptide and neurotransmitter that regulates food intake and gastric motility. The central nucleus of the amygdala (CeA), which regulates feeding behavior and gastric function, expresses the orexin-1 receptor. The aim of this study was to evaluate the effects of microinjection of exogenous orexin-A into the CeA, on food intake and gastric motility, and to explore the mechanisms of these effects. Normal chow and high fat food (HFF) intake were measured, gastric motility and gastric emptying were evaluated, extracellular single unit firing was recorded, and c-fos expression was determined. The results showed that microinjection of orexin-A into the CeA resulted in increased HFF intake but did not affect normal chow intake. This effect was blocked by an orexin-1 receptor antagonist-SB-334867 and was partially blocked by a dopamine D1 receptor antagonist-SCH-23390. Gastric motility and gastric emptying were enhanced by orexin-A, and the former effect was abolished by subdiaphragmatic vagotomy. The firing frequency of gastric distention-related neurons was regulated by orexin-A via the orexin-1 receptor. Furthermore, c-fos expression was increased in the ventral tegmental area (VTA) and the nucleus accumbens (NAc), the lateral hypothalamus (LHA), and the dorsal motor nucleus of the vagus (DMV) in response to microinjection of orexin-A into the CeA. These findings showed that orexin-A regulated palatable food intake and gastric motility via the CeA. The LHA, the VTA, and the NAc may participate in palatable food intake and the CeA-DMV-vagus-stomach pathway may be involved in regulating gastric motility through the regulation of neuronal activity in the CeA.

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ObjectiveThe tumor necrosis factor (TNF) and the cellular NF-κB pathway protein IKKβ play important roles in various cellular processes such as cell proliferation, survival, differentiation, and apoptosis. A heat shock protein 90 inhibitor, 17-DMAG, can induce apoptosis of some tumor cells. This study is to determine the combined effects of 17-DMAG and TNF on malignant cells and the related mechanisms.MethodsWe have determined effects of 17-DMAG, an Hsp90 inhibitor, and TNF treatments on the small cell lung cancer cell line (MS-1), the adenocarcinoma cell line (A549), the squamous-cell carcinoma cell line (LK-2), and the normal human bronchial epithelium cell line (NuLi-1) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrozolium bromide assay. To determine if 17-DMAG inhibit the expression of IKKβ in the normal human NuLi-1 cells, and the malignant MS-1, A549, and LK-2 cells, immunoblotting assays and luciferase assays were performed.ResultsIt was found that the combined treatments resulted in synergistic killing of malignant cells, which was confirmed by the apoptosis determination using a fluorescence microscopic assay following staining of the drug-treated cells with Hoescht 33258. The immunoblotting results indicated that the synergistic killing due to 17-DMAG and TNF treatments may be related to the decreases in IKKβ levels in the presence of 17-DMAG.ConclusionsThe results suggest that combination of 17-DMAG and TNF treatments might be useful for treating malignancies upon further study in the further.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2041198513886824

Soil salinization and acidification seriously damage soil health and restricts the sustainable development of planting. Excessive application of chemical fertilizer and other reasons will lead to soil acidification and salinization. This study focus on acid and salinized soil, investigated the effect of phosphate-solubilizing bacteria, Aspergillus niger MJ1 combined with nitrogen-fixing bacteria Pseudomonas stutzeri DSM4166 or mutant Pseudomonas fluorescens CHA0-nif on crop quality, soil physicochemical properties, and microbial communities. A total of 5 treatments were set: regular fertilization (T1), regular fertilization with MJ1 and DSM4166 (T2), regular fertilization with MJ1 and CHA0-nif (T3), 30%-reducing fertilization with MJ1 and DSM4166 (T4), and 30%-reducing fertilization with MJ1 and CHA0-nif (T5). It was found that the soil properties (OM, HN, TN, AP, AK, and SS) and crop quality of cucumber (yield production, protein, and vitamin C) and lettuce (yield production, vitamin C, nitrate, soluble protein, and crude fiber) showed a significant response to the inoculated strains. The combination of MJ1 with DSM4166 or CHA0-nif influenced the diversity and richness of bacterial community in the lettuce-grown soil. The organismal system-, cellular process-, and metabolism-correlated bacteria and saprophytic fungi were enriched, which were speculated to mediate the response to inoculated strains. pH, OM, HN, and TN were identified to be the major factors correlated with the soil microbial community. The inoculation of MJ1 with DSM4166 and CHA0-nif could meet the requirement of lettuce and cucumber growth after reducing fertilization in acid and salinized soil, which provides a novel candidate for the eco-friendly technique to meet the carbon-neutral topic.

This study is to determine if PU-H71, a heat shock protein inhibitor, induces killing of malignant breast cells together with treatment of tumor necrosis factor-α (TNF-α). The related molecular mechanisms were also studied. A primary mammary epithelial cell line HMEC2595 cells and the highly metastatic breast cell line MDA-MB-231, the HER2-positive BT-474 cells, and the ER-positive MCF7 cells were treated with PU-H71 in the presence or absence of TNF-α. The effects of PU-H71 and TNF-α treatments on cells viabilities and on intracellular signaling pathway proteins were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assays, immunoblot assays, and luciferase assays. It was found that TNF-α enhances the toxic effects of PU-H71 on tumor cells but not normal cells. PU-H71 treatments lead to degradation of IKKβ. Moreover, PU-H71 down-regulates the NF-κB transcriptional activity induced by TNF-α treatment. The experimental results indicated PU-H71 effectively induces cell killing of malignant breast cells in the presence of TNF-α, possibly through a mechanism related to degradation of IKKβ. It is suggested that combination of PU-H71 and TNF-α treatments might be an effective therapeutic strategy of breast malignancies.