Multiscale anisotropy analysis of second-harmonic generation collagen imaging of mouse skin.

Significance: Morphological collagen signatures are important for tissue function, particularly in the tumor microenvironment. A single algorithmic framework with quantitative, multiscale morphological collagen feature extraction may further the use of collagen signatures in understanding fundamental tumor progression.

Aim: A modification of the 2D wavelet transform modulus maxima (WTMM) anisotropy method was applied to both digitally simulated collagen fibers and second-harmonic-generation imaged collagen fibers of mouse skin to calculate a multiscale anisotropy factor to detect collagen fiber organization.

An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.

The growth and spread of malignant tumors, such as ovarian carcinomas, are governed in part by complex interconnected signaling cascades occurring between stromal and tumor cells. These reciprocal cross-talk signaling networks operating within the local tissue microenvironment may enhance malignant tumor progression. Understanding how novel bioactive molecules generated within the tumor microenvironment regulate signaling pathways in distinct cellular compartments is critical for the development of more effective treatment paradigms.

Canonical WNT/β-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice.

The R-spondin (RSPO) family of proteins potentiate canonical WNT/β-catenin signaling and may provide a mechanism to fine-tune the strength of canonical WNT signaling. Although several studies have clearly demonstrated the potentiation of canonical WNT signaling by RSPOs, whether this potentiation actually occurs in normal development and tissue function still remains poorly understood. Here, we provide clear evidence of the potentiation of canonical WNT signaling by RSPO during mouse facial development by analyzing compound and gene knockout mice and utilizing facial explants.

Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis.

Structural remodeling of the extracellular matrix is a well-established process associated with tumor growth and metastasis. Tumor and stromal cells that compose the tumor mass function cooperatively to promote the malignant phenotype in part by physically interacting with intact and structurally altered matrix proteins. To this end, collagen represents the most abundant component of the extracellular matrix and is known to control the behavior of histologically distinct tumor types as well as a diversity of stromal cells.

Melanogenesis inhibitory pregnane glycosides from Cynanchum atratum.

Bioassay-guided fractionation of the methanolic extract from the roots of Cynanchum atratum has resulted in the isolation of three new pregnane glycosides (1-3) along with four known compounds (4-7). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for their potential to inhibit the melanin production in α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells.

Regulation of the follistatin gene by RSPO-LGR4 signaling via activation of the WNT/β-catenin pathway in skeletal myogenesis.

WNT signaling plays multiple roles in skeletal myogenesis during gestation and postnatal stages. The R-spondin (RSPO) family of secreted proteins and their cognate receptors, members of leucine-rich repeat-containing G protein-coupled receptor (LGR) family, have emerged as new regulatory components of the WNT signaling pathway. We previously showed that RSPO2 promoted myogenic differentiation via activation of WNT/β-catenin signaling in mouse myoblast C2C12 cells in vitro.

Absence of a major role for the snai1 and snai3 genes in regulating skeletal muscle regeneration in mice.

The Snail gene family encodes DNA-binding zinc finger proteins that function as transcriptional repressors. While the Snai1 and Snai2 genes are required for normal development in mice, Snai3 mutant mice exhibit no obvious abnormalities. The Snai3 gene is expressed at high levels in skeletal muscle.

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α.

Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts.

Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and maxillary processes during upper jaw and lip development.

Outgrowth and fusion of the lateral and medial nasal processes and of the maxillary process of the first branchial arch are integral to lip and primary palate development. Wnt9b mutations are associated with cleft lip and cleft palate in mice; however, the cause of these defects remains unknown. Here, we report that Wnt9b(-/-) mice show significantly retarded outgrowth of the nasal and maxillary processes due to reduced proliferation of mesenchymal cells, which subsequently results in a failure of physical contact between the facial processes that leads to cleft lip and cleft palate.

Novel iridoids from the flowers of Campsis grandiflora.

A non-glycosidic iridoid, campsinol (1), and two iridoid glucosides, 7-O-(Z)-p-coumaroylcachineside V (2) and 7-O-(E)-p-coumaroylcachineside I (3), were isolated from the fresh flowers of Campsis grandiflora along with five known iridoid glycosides, ixoroside (4), campsiside (5), cachineside I (6), 5-hydroxycampenoside (7), and 5-hydroxycampsiside (8), and two known phenylpropanoid glycosides, acteoside (9) and leucosceptoside A (10). The structures of these compounds were determined based on the NMR and Mass spectroscopic data and other chemical evidences.

Antioxidative oligostilbenes from Caragana sinica.

Two new oligostilbenes, caragasinins A (5) and B (10), and eight known compounds, kobophenol A (1), (+)-α-viniferin (2), (+)-ampelopsin F (3), pallidol (4), (+)-isoampelopsin F (6), miyabenol C (7), carasinaurone (8) and caraphenol B (9) were isolated from the ethylacetate-soluble extract of the roots of Caragana sinica. The structures of the isolates were determined on the basis of extensive spectroscopic analysis including 1D, 2D NMR and HRESI-MS. These compounds were assessed for antioxidant activities.

Inhibitory constituents of Nardostachys chinensis on nitric oxide production in RAW 264.7 macrophages.

The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4α,5-dimethyl-1,3-dioxo-1,2,3,4,4α,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.

Dimeric ent-kaurane diterpenoids from Isodon excisus.

Five new dimeric ent-kauranoids, biexcisusins A-E (1-5), were isolated from the aerial parts of Isodon excisus. The structures and relative configurations of these compounds were determined on the basis of spectroscopic data interpretation. Of these, biexcisusins C-E (3-5) are dimeric ent-kaurane diterpenoids exhibiting an unprecedented linkage through a nine-membered lactone ring between two ent-kaurane subunits.

Pyrrolidinone diterpenoid from Isodon excisus and inhibition of nitric oxide production in lipopolysaccharide-induced macrophage RAW264.7 cells.

A new pyrrolidinone diterpenoid, excisusin F (1), was isolated from the aerial parts of Isodon excisus (Lamiaceae), together with four known compounds, and their structures were determined mainly by NMR (1D and 2D) and mass spectrometry. Excisusin F (1) and inflexarabdonin E (3) showed potent inhibitory effects of LPS-induced nitric oxide production in RAW264.7 cells with the IC(50) value of 10.

A WNT/beta-catenin signaling activator, R-spondin, plays positive regulatory roles during skeletal myogenesis.

R-spondins (RSPOs) are a recently characterized family of secreted proteins that activate WNT/β-catenin signaling. In this study, we investigated the potential roles of the RSPO proteins during myogenic differentiation. Overexpression of the Rspo1 gene or administration of recombinant RSPO2 protein enhanced mRNA and protein expression of a basic helix-loop-helix (bHLH) class myogenic determination factor, MYF5, in both C2C12 myoblasts and primary satellite cells, whereas MYOD or PAX7 expression was not affected.

The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction.

R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate.

Synthesis and Magnetic Properties of Nearly Monodisperse CoFe2O4Nanoparticles Through a Simple Hydrothermal Condition.

Nearly monodisperse cobalt ferrite (CoFe2O4) nanoparticles without any size-selection process have been prepared through an alluring method in an oleylamine/ethanol/water system. Well-defined nanospheres with an average size of 5.5 nm have been synthesized using metal chloride as the law materials and oleic amine as the capping agent, through a general liquid-solid-solution (LSS) process.

Phenanthrenes from Dendrobium nobile and their inhibition of the LPS-induced production of nitric oxide in macrophage RAW 264.7 cells.

Bioactivity-guided isolation of the methanol extract of the stems of Dendrobium nobile yielded a new phenanthrene together with nine known phenanthrenes and three known bibenzyls. Their structures were elucidated by analysis of the spectroscopic data including 2D-NMR. All of the isolates were evaluated for their potential to inhibit the LPS-induced production of nitric oxide in murine macrophage RAW 264.

Catalponol enhances dopamine biosynthesis and protects against L-DOPA-induced cytotoxicity in PC12 cells.

The effects of catalponol (1) on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalponol at concentration ranges of 1-5 microM increased the intracellular levels of dopamine at 12-48 h. Catalponol at concentrations of up to 10 microM did not alter cell viability.

Prenylated and benzylated flavonoids from the fruits of Cudrania tricuspidata.

Three new prenylated isoflavones, 5,7-dihydroxy-6-(2''-hydroxy-3''-methylbut-3''-enyl)-4'-methoxylisoflavone (1), 5,4'-dihydroxy-6-(3''-methylbut-2''-enyl)-2'''-(4'''-hydroxy-4'''-methylethyl)-3'''-methoxydihydrofurano-[4''',5''';7,8]isoflavone (2), and 5,4'-dihydroxy-8-(3''-methylbut-2''-enyl)-2'''-(4'''-hydroxy-4'''-methylethyl)furano-[4''',5''';6,7]isoflavone (3), a benzylated dihydroflavonol, 5,7,4'-trihydroxy-8-p-hydroxybenzyldihydroflavonol (4), and eight known flavonoids (5-12) were isolated from the fruits of Cudrania tricuspidata. The structures of these compounds were determined on the basis of MS and (1)H and (13)C NMR spectroscopic data, including 2D NMR experiments. Compounds 2, 3, 6, 7, 8, 10, 11, and 12 inhibited LPS-induced nitric oxide production, with IC(50) values of 11.

Antiplatelet activity of beta-carboline alkaloids from Perganum harmala: a possible mechanism through inhibiting PLCgamma2 phosphorylation.

Beta-carboline alkaloids including harmalol, harmaline, norharmane, harmol, harmine and harmane are important constituents of the medicinal plant, Perganum harmala L. (Zygophylaceae), which has been used in traditional medicine. In the present study, the antiplatelet activities of six beta-carboline alkaloid compounds were investigated in vitro.

A new abietane diterpenoid from Isodon inflexus.

A new ent-abietane diterpenoid, 3alpha,6beta-dihydroxy-7,17-dioxo-ent-abieta-15(16)-ene (1), and three known ent-kaurane diterpenids, kamebacetal A (2), kamebakaurin (3), and excisanin A (4), and a known triterpenoid, ursolic acid (5), were isolated from the aerial parts of Isodon inflexus. Their chemical structures were determined by extensive analysis of spectroscopic data including 1D-and 2D-NMR experiments. All isolates (1-5) were evaluated for their potential to inhibit LPS-induced nitric oxide production in RAW264.

Effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.

The effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalpalactone at 5-30μM decreased intracellular dopamine content with the IC(50) value of 22.1μM.

Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase.

We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P.