Suncheonosides A–D, Benzothioate Glycosides from a Marine-Derived <i>Streptomyces</i> sp.

A marine-derived <i>Streptomyces</i> strain, SSC21, was isolated from the sediment of Suncheon Bay, Republic of Korea. Chemical analysis of the bacterial strain resulted in the isolation of four new metabolites, suncheonosides A–D (<b>1–4</b>, respectively), each bearing a sulfur atom. The planar structures of the suncheonosides were identified as hexasubstituted benzothioate glycosides by combined spectroscopic analyses. Analysis of the configuration of the sugar moieties based on ROESY nuclear magnetic resonance correlations, one-bond ¹H–¹³C coupling constant analysis, and chemical derivatizations indicated that the suncheonosides incorporate only l-rhamnose. Suncheonosides A, B, and D promoted adiponectin production in a concentration-dependent manner during adipogenesis in human mesenchymal stem cells, suggesting antidiabetic potential

Computational Prediction of the Phenotypic Effect of Flavonoids on Adiponectin Biosynthesis

In silico machine learning applications for phenotype-based screening have primarily been limited due to the lack of machine-readable data related to disease phenotypes. Adiponectin, a nuclear receptor (NR)-regulated adipocytokine, is relatively downregulated in human metabolic diseases. Here, we present a machine-learning model to predict the adiponectin-secretion-promoting activity of flavonoid-associated phytochemicals (FAPs). We modeled a structure–activity relationship between the chemical similarity of FAPs and their bioactivities using a random forest-based classifier, which provided the NR activity of each FAP as a probability. To link the classifier-predicted NR activity to the phenotype, we next designed a single-cell transcriptomics-based multiple linear regression model to generate the relative adiponectin score (RAS) of FAPs. In experimental validation, estimated RAS values of FAPs isolated from Scutellaria baicalensis exhibited a significant correlation with their adiponectin-secretion-promoting activity. The combined cheminformatics and bioinformatics approach enables the computational reconstruction of phenotype-based screening systems

Computational Prediction of the Phenotypic Effect of Flavonoids on Adiponectin Biosynthesis

In silico machine learning applications for phenotype-based screening have primarily been limited due to the lack of machine-readable data related to disease phenotypes. Adiponectin, a nuclear receptor (NR)-regulated adipocytokine, is relatively downregulated in human metabolic diseases. Here, we present a machine-learning model to predict the adiponectin-secretion-promoting activity of flavonoid-associated phytochemicals (FAPs). We modeled a structure–activity relationship between the chemical similarity of FAPs and their bioactivities using a random forest-based classifier, which provided the NR activity of each FAP as a probability. To link the classifier-predicted NR activity to the phenotype, we next designed a single-cell transcriptomics-based multiple linear regression model to generate the relative adiponectin score (RAS) of FAPs. In experimental validation, estimated RAS values of FAPs isolated from Scutellaria baicalensis exhibited a significant correlation with their adiponectin-secretion-promoting activity. The combined cheminformatics and bioinformatics approach enables the computational reconstruction of phenotype-based screening systems

Computational Prediction of the Phenotypic Effect of Flavonoids on Adiponectin Biosynthesis

In silico machine learning applications for phenotype-based screening have primarily been limited due to the lack of machine-readable data related to disease phenotypes. Adiponectin, a nuclear receptor (NR)-regulated adipocytokine, is relatively downregulated in human metabolic diseases. Here, we present a machine-learning model to predict the adiponectin-secretion-promoting activity of flavonoid-associated phytochemicals (FAPs). We modeled a structure–activity relationship between the chemical similarity of FAPs and their bioactivities using a random forest-based classifier, which provided the NR activity of each FAP as a probability. To link the classifier-predicted NR activity to the phenotype, we next designed a single-cell transcriptomics-based multiple linear regression model to generate the relative adiponectin score (RAS) of FAPs. In experimental validation, estimated RAS values of FAPs isolated from Scutellaria baicalensis exhibited a significant correlation with their adiponectin-secretion-promoting activity. The combined cheminformatics and bioinformatics approach enables the computational reconstruction of phenotype-based screening systems

Selenoacyclovir and Selenoganciclovir: Discovery of a New Template for Antiviral Agents

On the basis of the potent antiviral activity of acyclovir and ganciclovir, selenoacyclovir (<b>2a</b>) and selenoganciclovir (<b>2b</b>) were designed based on bioisoteric rationale and synthesized via the diselenide <b>7</b> as the key intermediate. Compound <b>2a</b> exhibited potent anti-HSV-1 and -2 activities while <b>2b</b> exerted moderate anti-HCMV activity, indicating that these nucleosides can serve as a novel template for the development of new antiviral agents

Tumor xenografts derived from ABCG2+ and ABCG2- IGR39 cells.

<p>5×10⁵ unsorted, ABCG2+ or ABCG2- sorted cells were injected subcutaneously in five-week-old NOD-SCID mice (3 mice for each experimental condition). After 60 days, the tumor mass was excised weighed and photographed.</p

Mean tumor weight ± SD (n = 3).

<p>Mean tumor weight ± SD (n = 3).</p

Demonstration of the asymmetric self-renewal associated (ASRA) biomarker properties of CXCR6.

<p>Shown are examples of epifluorescence and phase contrast micrographs from parallel <b>SP</b> and <b>CD</b> analyses, as described in the text. <b>SYM</b>, symmetric self-renewal (Congenic p53-null engineered cell lines grown in ZnCl₂-supplemented medium). <b>ASYM</b>, asymmetric self-renewal (Zn-dependent, p53-inducible engineered cells grown in ZnCl₂-supplemented medium). <b>DNA</b>, DAPI nuclear DNA fluorescence. <b>CyA</b>, indirect ISIF with specific antibodies for cyclin A. <b>CXCR6</b>, indirect ISIF with specific antibodies for CXCR6. Note that in the ASYM state, CXCR6 is up-regulated in the cycling cell, which models asymmetrically self-renewing TSSCs. <b>Phase</b>, phase contrast micrograph. <b>Scale bar</b>  = 50 microns.</p

Tumor xenografts derived from and CXCR6- IGR37 cells.

<p>5×10⁵ CXCR6- sorted cells were injected subcutaneously in five-week-old NOD-SCID mice (3 mice for each experimental condition). CXCR6- cells did not yield tumors.</p

Flow cytometry detection and sorting of CXCR6+ subpopulations from cultures of human melanoma cell lines.

<p>Dual marker analyses for CXCR6 and ABCG2. Primary melanoma IGR39 cells and metastatic melanoma IGR37 cells were incubated with the indicated fluorescent APC-conjugated antibodies and analyzed by flow cytometry as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015183#s4" target="_blank"><i>Materials and Methods</i></a>. <b>Left panels</b>, bivariate fluorescence intensity analyses with respective APC- and FITC-conjugated isotype (IgG) control antibodies; <b>middle panels</b>, bivariate fluorescence intensity analyses with respective APC- and FITC-conjugated CXCR6-specific and ABCG2-specific antibodies. <b>Numbers</b>, percent of total evaluated cells.</p