Sterols from the Green Alga Ulva australis.

Three new sterols, (24R)-5,28-stigmastadiene-3ß,24-diol-7-one (1), (24S)-5,28-stigmastadiene-3ß,24-diol-7-one (2), and 24R and 24S-vinylcholesta-3ß,5α,6ß,24-tetraol (3), together with three known sterols (4-6) were isolated from the green alga Ulva australis. The structures of the new compounds (1-3) were elucidated through 1D and 2D nuclear magnetic resonance spectroscopy as well as mass spectrometry. Compounds 4-6 were identified as isofucoterol (4), 24R,28S and 24S,28R-epoxy-24-ethylcholesterol (5), and (24S)-stigmastadiene-3ß,24-diol (6) on the basis of spectroscopic data analyses and comparison with those reported in the literature. Compounds 4-6 were isolated from U. australis for the first time. These compounds, together with the previously isolated secondary metabolites of this alga, were investigated for their inhibitory effects on human recombinant aldose reductase in vitro. Of the compounds, 24R,28S and 24S,28R-epoxy-24-ethylcholesterol (5), 1-O-palmitoyl-3-O-(6'-sulfo-α-d-quinovopyranosyl) glycerol, (2S)-1-O-palmitoyl-3-O-[α-d-galactopyranosyl(1→2)ß-d-galactopyranosyl] glycerol, 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, and 8-hydroxy-(6E)-octenoic acid weakly inhibited the enzyme, while the three new sterols, 1-3, were almost inactive.

Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in hepatocellular carcinoma by control of epithermal growth factor receptor-induced epithelial-mesenchymal transition.

UNLABELLED: Hepatocellular carcinoma (HCC) is the third-most lethal cancer worldwide. Understanding the molecular pathogenesis of HCC recurrence and metastasis is the key to improve patients' prognosis. In this study, we report that protein tyrosine phosphatase receptor S (PTPRS) is significantly down-regulated in nearly 80% of HCCs, and its expression negatively correlates with aggressive pathological features, such as larger tumor size and advanced stage. In addition, PTPRS deficiency is independently associated with shorter survival and increased recurrence in patients, although 16.7% of HCCs show intratumor heterogeneous expression of PTPRS. Restoration of wild-type, but not mutant, PTPRS expression significantly inhibits HCC cell migration and invasion in vitro as well as lung metastasis in vivo, whereas knockdown of its expression significantly promotes invasion and metastasis. Notably, PTPRS-regulated HCC invasiveness is accompanied by typical changes of epithelial-mesenchymal transition (EMT). Moreover, PTPRS forms a complex with epithermal growth factor receptor (EGFR) and regulates its tyrosine residues' phosphorylation. Ectopic expression of EGFR reverses the metastasis-inhibiting effects of PTPRS, whereas silencing of EGFR or inhibiting phosphorylation of key molecules in EGFR downstream pathways reinhibits EMT and metastasis caused by PTPRS down-regulation. Meanwhile, promoter hypermethylation of PTPRS is frequently detected in HCC samples and cell lines. Treatment with a demethylation agent, 5-aza-2'-deoxycytidine, recovers PTPRS expression in a dose-dependent manner. CONCLUSIONS: Epigenetic inactivation of PTPRS may increase phosphorylation and activity of EGFR signaling to promote EMT and metastasis in HCC.

Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients.

BACKGROUND & AIMS: The pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second most common hepatic cancer, is poorly understood, and the incidence of ICC is increasing worldwide. We searched for mutations in human ICC tumor samples and investigated how they affect ICC cell function. METHODS: We performed whole exome sequencing of 7 pairs of ICC tumors and their surrounding nontumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and nontumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). RESULTS: Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4 of 7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1 of 9 PTP genes; 41.1% had mutations in PTPN3. Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3(L232R) and PTPN3(L384H), which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than nontumor tissues had higher rates of disease recurrence than patients whose tumors did not have these characteristics. CONCLUSIONS: Using whole exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3. Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence.

[Application of near-infrared spectroscopy to quality detection of milk and its products].

Milk and its products as a kind of ideal comprehensive nutritional food, has becoming an indispensable part of people's daily, life. But at the same time, the quality of dairy products has been also increasingly concerned by consumers. Real-time, rapid and accurate detection of milk and its products in terms of component, adulterants, residues and preservatives is the primary condition for improving the dairy products quality and controlling the production process. Quality predication of milk and its products was often completed by laboratory analysis in the past, which was complicated and time-consuming and could not satisfy the needs for evaluating the milk products quality and monitoring the production proceeding effectively. How to predict the quality of milk and its products quickly and accurately is a practical problem that needs to be resolved. Near-infrared spectroscopy (NIRS) is a rapid, convenient, highly efficient, non-destructive and low-cost analytical technique, which has been widely used in various fields for quantitative and qualitative analysis. As a new analysis technique, NIRS has great potential of application to milk and its products detection, owning to its quick, concise and non--destructive characteristics. The main nutrient components were the major index of milk and its products quality evaluation. Determining the main nutrient components of milk and its products rapidly can provide sound basis for evaluating the products quality. At the same time, adulterants, residues and preservatives were also distinct fingerprint characteristics in the NIR spectra just like the main nutrient components. So this new approaches could also be used in quality distinguishing and on-line detection of milk and its products. Many researches have also concluded that NIRS technology has good stability and high prediction ability on dairy products analysis, exhibites well correlation with the result by labor analysis method. In the present paper, the principles and advantages of NIRS were described. The research advancement of NIRS utilization for milk products nutrient component determination, quality estimation and on-line detection and the application prospect were comprehensively reviewed. With the development of spectral technique, the prediction model gained through NIRS will be more and more reliable and practicable, and the NIRS technique will be more widely used in milk and its products determination, quality estimation and on-line detection.

Perillanolides A and B, new monoterpene glycosides from the leaves of Perilla frutescens

Abstract Two new monoterpene glycosides, perillanolides A and B, together with a known compound reported from the genus Perilla for the first time were isolated and characterized from the leaves of Perilla frutescens (L.) Britton, Lamiaceae, a garnish and colorant for foods as well as commonly used for traditional medicine. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic evidences derived from nuclear magnetic resonance experiments, mass spectrometry and by comparing their physical and spectroscopic data of literature. These compounds, together with the previously isolated secondary metabolites of this species, were investigated for their inhibitory effects on xanthine oxidase in vitro. Of the compounds, luteolin showed the strongest inhibitory activity with an IC50 value of 2.18 µM. Esculetin and scutellarein moderately inhibited the enzyme, while perillanolides A and B, and 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside exerted weak activities.