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The FoxP2 transcription factor and its target genes have been implicated in developmental brain diseases with a prominent language component, such as developmental verbal dyspraxia and specific language impairment. How FoxP2 affects neural circuitry development remains poorly understood. The sushi domain protein SRPX2 is a target of FoxP2, and mutations in SRPX2 are associated with language defects in humans. We have previously shown that SRPX2 is a synaptogenic protein that increases excitatory synapse density. Here we provide the first characterization of mice lacking the SRPX2 gene, and show that these mice exhibit defects in both neural circuitry and communication and social behaviors. Specifically, we show that mice lacking SRPX2 show a specific reduction in excitatory VGlut2 synapses in the cerebral cortex, while VGlut1 and inhibitory synapses were largely unaffected. SRPX2 KO mice also exhibit an abnormal ultrasonic vocalization ontogenetic profile in neonatal pups, and reduced preference for social novelty. These data demonstrate a functional role for SRPX2 during brain development, and further implicate FoxP2 and its targets in regulating the development of vocalization and social circuits. [ABSTRACT FROM AUTHOR]

Fucoidan may inhibit angiogenesis. However, its functional target molecule and the underlying mechanism are still vague. In the present study, we showed that sulfated fucoidan FP08S2 from Sargassum fusiforme inhibited tube formation as well as migration and invasion of human microvascular endothelial cells (HMEC-1). In addition, FP08S2 was confirmed to disrupt VEGF-induced angiogenesis both in vitro and in vivo. Further study indicated that FP08S2 could bind to both VEGF and VEGFR2 to interfere with VEGF-VEGFR2 interaction. Moreover, VEGFR2/Erk/VEGF signaling pathway was blocked by FP08S2 in HMEC-1 cells. Importantly, FP08S2 impeded the growth and microvessel formation of A549 cancer cell xenograft in nude mice. These results suggested that FP08S2 presented remarkable anti-angiogenic activity via blocking VEGF signaling and could be a potential novel leading compound to inhibit lung cancer cell growth. [ABSTRACT FROM AUTHOR]

A fucoidan FP08S2 was isolated from the boiling-water extract of Sargassum fusiforme , purified by CaCl 2 precipitation and chromatography on DEAE-cellulose and Sephacryl S-300. FP08S2 contained fucose, xylose, galactose, mannose, glucuronic acid, and 20.8% sulfate. The sulfate groups were attached to diverse positions of fucose, xylose, mannose, and galactose residues. The backbone of FP08S2 consisted of alternate 1,2-linked α- d -Man p and 1,4-linked β- d -Glc p A. Sugar composition analysis and ESI-MS revealed that the oligosaccharides from branches contained fucose, xylose, galactose, glucuronic acid and sulfate. FP08S2 could significantly inhibit tube formation and migration of human microvascular endothelial cells (HMEC-1) dose-dependently. These results suggested that the fucoidan FP08S2 from brown seaweeds S. fusiforme could be a potent anti-angiogenic agent. [ABSTRACT FROM AUTHOR]

An alginate fraction, 04S2P, was isolated from the brown seaweed Sargassum fusiforme and was structurally characterized by the ratio ( M / G ) of β- d -mannuronic acid residues (M) to α- l -guluronic acid residues (G) via 1 H and 13 C NMR spectroscopy. When compared to commercial alginate (Alg) and alginates from other brown algae, 04S2P has a higher M / G ratio of 9.0:1.0 as determined by a modified high-performance liquid chromatography method after pre-column derivatization with PMP. Furthermore, the sulfated polysaccharides 04S2P-S and Alg-S were prepared by the chlorosulfonic acid-pyridine method. Both C-2 and/or C-3 of M and G residues of 04S2P-S were substituted by sulfate groups, with C-3 of M residues preferentially substituted. Their effects on tube formation of HMEC-1 cells were examined, and the results indicated that the sulfated Alg, Alg-S, exhibited a strong anti-angiogenic effect on HMEC-1 cells. The anti-tumor activity of native and sulfated alginates was tested on five different tumor cell lines. Alg-S demonstrated significant anti-tumor effects on the Bel7402, SMMC7721, and HT-29 cell lines, whereas 04S2P-S showed a distinct anti-tumor effect only on the Bel7402 cell line. [ABSTRACT FROM AUTHOR]

Highlights: [•] COB1B1S2 was extracted from Cassia obtusifolia seeds. [•] COB1B1S2 is a novel glucuronoxylan without methylation at O-4 of GlcA. [•] COB1B1S2-sul inhibited tube formation of HMEC-1 cells. [•] COB1B1S2-sul inhibited the proliferation of Bel7402 human hepatoma cells. [Copyright &y& Elsevier]

To investigate polysaccharide structure from Lonicera japonica , and study its effects on behavior of pancreatic cells, a homogenous polysaccharide, LJ-02-1, was extracted and purified from flowers of L. japonica by DEAE-cellulose and Sephacryl S-200HR column. The molecular weight was estimated to be 54 kDa. Monosaccharide composition was determined to be rhamnose, galacturonic acid, galactose and arabinose in the molar ratio of 10.77:7.88:15.45:65.89 by analyzing the PMP derivatives of the monosaccharides from 2 M trifluoracetic acid hydrolysis via HPLC. Based on methylation analysis, partial acid hydrolysis, and NMR spectra, the polysaccharide was elucidated to be a rhamnogalacturonan backbone and substituted partly at C-4 of rhamnose. The branches were determined to be T- and 1,4,6-linked β- d -Gal p , T- and 1,5-linked α- l -Ara f . The polysaccharide might inhibit BxPC-3 and PANC-1 pancreatic cancer cells growth at the concentration of 1 mg/mL with inhibitory ratio of 66.7% and 52.1%, respectively. [ABSTRACT FROM AUTHOR]

A sulfated and acetylated fucoidan, named NDH01, was extracted from seaweed Nemacystus decipiens . NDH01 was composed of mannose, glucuronic acid, fucose, sulfate group and acetyl group in the molar ratio of 3.0: 14.4: 82.6: 34.3: 13.9. The backbone of NDH01 was fucose-free core, composed of α- d -1,2-Man p and β- d -1,4-Glc p A disaccharide repeat unit. The branches were attached at the C3, C4 and C6 of α- d -1,2-Man p . The sidechain was composed of α- l -1,3,4-Fuc p , α- l -1,4-Fuc p , α- l -1,3-Fuc p and α- l -1,4-Glc p A. The sulfate group was linked to C4 of α- l -1,3,4-Fuc p , whereas, acetyl group was branched on C2 of α- l -1,2,3-Fuc p . NDH01 could disrupt tube formation and inhibit the migration as well as cell growth of human microvascular endothelial cells. Besides, phosphorylation of Smad/1/5/8, Erk and FAK was significantly inhibited by NDH01. Further studies uncovered that NDH01 blocked Smad1/5/8 signaling via interacting with bone morphogenetic protein 4 and downregulating bone morphogenetic protein 4 expression. The results suggested that NDH01 might be an angiogenesis inhibitor through targeting bone morphogenetic protein 4. [ABSTRACT FROM AUTHOR]

The flowers of Chrysanthemum morifolium were extracted by boiling water, and a water-soluble polysaccharide (CMJA0S2) with a molecular weight of 6.5 kDa was isolated by anion-exchange chromatography on a DEAE-cellulose column and gel permeation chromatography on a Sephacryl S-300 HR column. Monosaccharide composition analysis indicated that CMJA0S2 was composed of galactose, glucose, mannose and arabinose in molar ratio of 4.1: 3.3: 1.0: 2.3. According to linkage analysis, partial acid hydrolysis and NMR spectra, the backbone was shown to contain 1, 4-linked β-Gal p , 1, 4-linked β-Glc p and 1, 4-linked β-Man p , with branches substituted at C-6 of 1, 4-linked β-Man p by 1, 6-linked β-Gal p and at O-6 of partial 1, 4-linked β-Gal p substituted by T-linked α-Glc p . About 40% of 1, 6-linked β-Gal p with T-linked α-Glc p was substituted at O-3 by α-Ara f -(1 → [5)-α-Ara f -(1] 3 . The anti-oxidative analysis showed that CMJA0S2 could scavenge the DPPH radicals and relieve the damage of PC12 cells caused by H 2 O 2 , thus it could be regarded as a potential natural antioxidant. [ABSTRACT FROM AUTHOR]