Antioxidant activity and growth inhibition of human colon cancer cells by crude and purified fucoidan preparations extracted from Sargassum cristaefolium

AbstractFucose-containing sulfated polysaccharides, also termed “fucoidans”, which are known to possess antioxidant, anticoagulant, anticancer, antiviral, and immunomodulating properties, are normally isolated from brown algae via various extraction techniques. In the present study, two methods (SC1 and SC2) for isolation of fucoidan from Sargassum cristaefolium were compared, with regard to the extraction yields, antioxidant activity, and inhibition of growth of human colon cancer cells exhibited by the respective extracts. SC1 and SC2 differ in the number of extraction steps and concentration of ethanol used, as well as the obtained sulfated polysaccharide extracts, namely, crude fucoidan preparation (CFP) and purified fucoidan preparation (PFP), respectively. Thin layer chromatography, Fourier transform infrared analysis, and measurements of fucose and sulfate contents revealed that the extracts were fucoidan. There was a higher extraction yield for CFP, which contained less fucose and sulfate but more uronic acid, and had weaker antioxidant activity and inhibition of growth in human colon cancer cells. In contrast, there was a lower extraction yield for PFP, which contained more fucose and sulfate but less uronic acid, and had stronger antioxidant activity and inhibition of growth in human colon cancer cells. Thus, since the difference in bioactive activities between CFP and PFP was not remarkable, the high extraction yield of SC1 might be favored as a method in industrial usage for extracting fucoidan

Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin

<p>Abstract</p> <p>Background</p> <p>The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins.</p> <p>Results</p> <p>We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation.</p> <p>Conclusion</p> <p>These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.</p

Oromotor variability in children with mild spastic cerebral palsy: a kinematic study of speech motor control

<p>Abstract</p> <p>Background</p> <p>Treating motor speech dysfunction in children with CP requires an understanding of the mechanism underlying speech motor control. However, there is a lack of literature in quantitative measures of motor control, which may potentially characterize the nature of the speech impairments in these children. This study investigated speech motor control in children with cerebral palsy (CP) using kinematic analysis.</p> <p>Methods</p> <p>We collected 10 children with mild spastic CP, aged 4.8 to 7.5 years, and 10 age-matched children with typical development (TD) from rehabilitation department at a tertiary hospital. All children underwent analysis of percentage of consonants correct (PCC) and kinematic analysis of speech tasks: poly-syllable (PS) and mono-syllable (MS) tasks using the Vicon Motion 370 system integrated with a digital camcorder. Kinematic parameters included spatiotemporal indexes (STIs), and average values and coefficients of variation (CVs) of utterance duration, peak oral opening displacement and velocity. An ANOVA was conducted to determine whether PCC and kinematic data significantly differed between groups.</p> <p>Results</p> <p>CP group had relatively lower PCCs (80.0-99.0%) than TD group (<it>p </it>= 0.039). CP group had higher STIs in PS speech tasks, but not in MS tasks, than TD group did (<it>p </it>= 0.001). The CVs of utterance duration for MS and PS tasks of children with CP were at least three times as large as those of TD children (<it>p </it>< 0.01). However, average values of utterance duration, peak oral opening displacement and velocity and CVs of other kinematic data for both tasks did not significantly differ between two groups.</p> <p>Conclusion</p> <p>High STI values and high variability on utterance durations in children with CP reflect deficits in relative spatial and/or especially temporal control for speech in the CP participants compared to the TD participants. Children with mild spastic CP may have more difficulty in processing increased articulatory demands and resulted in greater oromotor variability than normal children. The kinematic data such as STIs can be used as indices for detection of speech motor control impairments in children with mild CP and assessment of the effectiveness in the treatment.</p

Dry Needling at Myofascial Trigger Spots of Rabbit Skeletal Muscles Modulates the Biochemicals Associated with Pain, Inflammation, and Hypoxia

Background and Purpose. Dry needling is an effective therapy for the treatment of pain associated with myofascial trigger point (MTrP). However, the biochemical effects of dry needling that are associated with pain, inflammation, and hypoxia are unclear. This study investigated the activities of β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF after different dosages of dry needling at the myofascial trigger spots (MTrSs) of a skeletal muscle in rabbit. Materials and Methods. Dry needling was performed either with one dosage (1D) or five dosages (5D) into the biceps femoris with MTrSs in New Zealand rabbits. Biceps femoris, serum, and dorsal root ganglion (DRG) were sampled immediately and 5 d after dry needling for β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF immunoassays. Results. The 1D treatment enhanced the β-endorphin levels in the biceps femoris and serum and reduced substance P in the biceps femoris and DRG. The 5D treatment reversed these effects and was accompanied by increase of TNF-α, COX-2, HIF-1α, iNOS, and VEGF production in the biceps femoris. Moreover, the higher levels of these biochemicals were still maintained 5 d after treatment. Conclusion. Dry needling at the MTrSs modulates various biochemicals associated with pain, inflammation, and hypoxia in a dose-dependent manner

Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation

Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety