Dietary supplementation of ß-1, 3-glucan improves the intestinal health of white shrimp (Litopenaeus vannamei) by modulating intestinal microbiota and inhibiting inflammatory response.

The phenomenon of intestinal dysfunction is widely observed in white shrimp (Litopenaeus vannamei) culture, and ß-1,3-glucan has been confirmed to be beneficial in intestinal health with a lack understanding of its underlying mechanism. Proteobacteria, Firmicutes, and Actinobacteria served as the predominant phyla inhabiting the intestine of white shrimp, whilst a significant variation in their proportion was recorded in shrimp fed with basal and ß-1,3-glucan supplementation diets in this study. Dietary supplementation of ß-1,3-glucan could dramatically increase the microbial diversity and affect microbial composition, concurrent with a notable reduction in the ratio of opportunistic pathogen Aeromonas, gram-negative microbes, from Gammaproteobacteria compared to the basal diet group. The benefits for microbial diversity and composition by ß-1,3-glucan improved the homeostasis of intestinal microbiota through the increase of specialists' number and inhibition of microbial competition caused by Aeromonas in ecological networks; afterward, the inhibition of Aeromonas by ß-1,3-glucan diet dramatically suppressed microbial metabolism related to lipopolysaccharide biosynthesis, followed by a conspicuous decrease in the intestinal inflammatory response. The improvement of intestinal health referred to the elevation in intestinal immune and antioxidant capacity, ultimately contributing to the growth of shrimp fed ß-1,3-glucan. These results suggested that ß-1,3-glucan supplementation improved the intestinal health of white shrimp through the modulation of intestinal microbiota homeostasis, the suppression of intestinal inflammatory response, and the elevation of immune and antioxidant capacity, and subsequently promoted the growth of white shrimp.

Guttiferone K suppresses cell motility and metastasis of hepatocellular carcinoma by restoring aberrantly reduced profilin 1.

Hepatocellular carcinoma (HCC) is an aggressive malignancy and the 5-year survival rate of advanced HCC is < 10%. Guttiferone K (GUTK) isolated from the Garcinia genus inhibited HCC cells migration and invasion in vitro and metastasis in vivo without apparent toxicity. Proteomic analysis revealed that actin-binding protein profilin 1 (PFN1) was markedly increased in the presence of GUTK. Over-expression of PFN1 mimicked the effect of GUTK on HCC cell motility and metastasis. The effect of GUTK on cell motility was diminished when PFN1 was over-expressed or silenced. Over-expression of PFN1 or incubation with GUTK decreased F-actin levels and the expression of proteins involved in actin nucleation, branching and polymerization. Moreover, a reduction of PFN1 protein levels was common in advanced human HCC and associated with poor survival rate. In conclusion, GUTK effectively suppresses the motility and metastasis of HCC cells mainly by restoration of aberrantly reduced PFN1 protein expression.

Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults.

Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific brain regions that occur in preclinical AD.

Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade.

Traditional medicinal herb Andrographis paniculata is known to possess anti-tumor activity, and its potential active compound is the diterpenoid lactone andrographolide (ANGL). In this study, we have found that ANGL inhibits tumor growth in nude mice bearing xenografted Hep3B cancer cells, concomitant with a reduction in tumor vessel counts. ANGL inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenic responses in vitro and neoangiogenesis in vivo. We also found that ANGL inhibits VEGFA-induced phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream targets such as the mitogen-activated protein kinases (MAPKs). ANGL interferes with the binding of VEGFA to VEGFR2, but has no effect on VEGFR2 kinase activity in vitro. Taken together, our results indicate that ANGL possesses anti-angiogenic activity which is mediated by preventing VEGFA-induced phosphorylation and activation of VEGFR2 and MAPKs. The present study indicates that ANGL can block tumor angiogenesis and therefore represents therapeutic potential for cancer treatment.

Notoginsenoside Ft1 activates both glucocorticoid and estrogen receptors to induce endothelium-dependent, nitric oxide-mediated relaxations in rat mesenteric arteries.

Panax notoginseng (Burk.) F.H. Chen has been used traditionally for the treatment of cardiovascular diseases. Notoginsenoside Ft1 (Ft1) is a bioactive saponin from the leaves of P. notoginseng. Experiments were designed to determine whether or not Ft1 is an endothelium-dependent vasodilator. Rat mesenteric arteries were suspended in organ chambers for the measurement of isometric tension during phenylephrine-induced contractions. The cyclic guanosine monophosphate (cGMP) level was assessed using enzyme immunoassay. The phosphorylation and protein expressions of endothelial nitric oxide synthase (eNOS), glucocorticoid receptors (GR), estrogen receptors beta (ERß), protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) were determined by Western blotting. The localization of GR and ERß were determined by immunofluorescence staining. Ft1 caused endothelium-dependent relaxations, which were abolished by l-NAME (inhibitor of nitric oxide synthases) and ODQ (inhibitor of soluble guanylyl cyclase). Ft1 increased the cGMP level in rat mesenteric arteries. GR and ERß were present in the endothelial layer and their antagonism by RU486 and PHTPP, respectively, inhibited Ft1-induced endothelium-dependent relaxations and phosphorylations of eNOS, Akt and ERK1/2. Inhibition of phosphoinositide-3-kinase (PI3K) by wortmannin and ERK1/2 by U0126 reduced Ft1-evoked relaxations and eNOS phosphorylation. Taken in conjunction, the present findings suggest that Ft1 stimulates endothelial GRs and ERßs with subsequent activation of the PI3K/Akt and ERK1/2 pathways in rat mesenteric arteries. This results in phosphorylation of eNOS and the release of NO, which activates soluble guanylyl cyclase in the vascular smooth muscle cells leading to relaxations.

Antitumor activity of Dioscorea bulbifera L. rhizome in vivo.

Antitumor activities of water extract (fraction A), ethanol extract (fraction B), ethyl acetate extract (fraction C), non-ethyl acetate extract (fraction D) and compound diosbulbin B isolated from Dioscorea bulbifera L. (DB) were investigated in vivo in this present study. The results showed that fractions B and C both decreased tumor weight in S180 and H22 tumor cells bearing mice, while fractions A and D had no such effect. Furthermore, fraction C altered the weight of spleen and thymus, and the amounts of total leukocytes, lymphocytes and neutrophils in tumor-bearing mice. Further results showed that compound diosbulbin B demonstrated anti-tumor effects in the dose-dependent manner at the dosage of 2 to 16 mg/kg without significant toxicity in vivo. Furthermore, on the basis of chemical analysis of the above extracts by high-performance liquid chromatography (HPLC) with a diode array detector (DAD), diosbulbin B was found to be the major antitumor bioactive component of DB. These results suggest that DB has potential anti-tumor effects which may be related to influencing the immune system for the first time, and the compound diosbulbin B is the major antitumor component of DB.

Critical roles of cellular glutathione homeostasis and jnk activation in andrographolide-mediated apoptotic cell death in human hepatoma cells.

Andrographolide (ANDRO), isolated from the traditional herbal medicine Andrographis paniculata, is reported to have the potential therapeutic effects for hepatocellular carcinoma (HCC) in our previous reports. Here, we investigated the mechanism of ANDRO-mediated apoptotic cell death, focusing on the involvement of cellular reduced glutathione (GSH) homeostasis and c-Jun NH(2) -Terminal kinase (JNK). Buthionine sulfoximine (BSO), an inhibitor of cellular GSH biosynthesis, significantly augmented ANDRO-induced cytotoxicity in hepatoma Hep3B and HepG2 cells. BSO depleted cellular GSH, and augmented ANDRO-induced apoptosis, inhibition of colony formation and JNK activation in Hep3B cells. All these effects could be reversed by GSH monoethyl ester (GSH.EE), whose deacetylation replenishes cellular GSH. BSO also augmented ANDRO-induced activation of apoptosis signal-regulating kinase 1 (ASK1), mitogen-activated protein kinase kinase-4 (MKK4) and c-Jun, which are all up-stream or down-stream signals of JNK. Further results showed that JNK inhibitor SP600125 and 420116 both reversed ANDRO-induced cytotoxicity, and SP600125 also decreased ANDRO-increased intracellular GSH and GCL activity. Finally, we showed that in nude mice bearing xenografted Hep3B tumors, BSO improved the inhibition of tumor growth by ANDRO. Taken together, our results suggest that there is a crosstalk between JNK activation and cellular GSH homeostasis, and ANDRO targets this to induce cytotoxicity in hepatoma cells.