Susceptibility of anthocyanins to ex vivo degradation in human saliva

a b s t r a c t Some fruits and their anthocyanin-rich extracts have been reported to exhibit chemopreventive activity in the oral cavity. Insights regarding oral metabolism of anthocyanins remain limited. Anthocyanin-rich extracts from blueberry, chokeberry, black raspberry, red grape, and strawberry were incubated ex vivo with human saliva from 14 healthy subjects. All anthocyanins were partially degraded in saliva. Degradation of chokeberry anthocyanins in saliva was temperature dependent and decreased by heating saliva to 80°C and after removal of cells. Glycosides of delphinidin and petunidin were more susceptible to degradation than those of cyanidin, pelargonidin, peonidin and malvidin in both intact and artificial saliva. Stability of di-and tri-saccharide conjugates of anthocyanidins slightly, but significantly, exceeded that of monosaccharide compounds. Ex vivo degradation of anthocyanins in saliva was significantly decreased after oral rinsing with antibacterial chlorhexidine. These results suggest that anthocyanin degradation in the mouth is structure-dependent and largely mediated by oral microbiota

A comparative analysis of the fluorescence properties of the wild-type and active site mutants of the hepatitis C virus autoprotease NS2-3

Hepatitis C virus encodes an autoprotease, NS2-3, which is required for processing of the viral polyprotein between the non-structural NS2 and NS3 proteins. This protease activity is vital for the replication and assembly of the virus and therefore represents a target for the development of anti-viral drugs. The mechanism of this auto-processing reaction is not yet clear but the protease activity has been shown to map to the C-terminal region of NS2 and the N-terminal serine protease region of NS3. The NS2-3 precursor can be expressed in Escherichia coli as inclusion bodies, purified as denatured protein and refolded, in the presence of detergents and the divalent metal ion zinc, into an active form capable of auto-cleavage. Here, intrinsic tryptophan fluorescence has been used to assess refolding in the wild-type protein and specific active site mutants. We also investigate the effects on protein folding of alterations to the reaction conditions that have been shown to prevent auto-cleavage. Our data demonstrate that these active site mutations do not solely affect the cleavage activity of the HCV NS2-3 protease but significantly affect the integrity of the global protein fold

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper

The immunomodulatory and antimicrobial properties of zinc and copper have long been appreciated. In addition, these metal ions are also essential for microbial growth and survival. This presents opportunities for the host to either harness their antimicrobial properties or limit their availability as defence strategies. Recent studies have shed some light on mechanisms by which copper and zinc regulation contribute to host defence, but there remain many unanswered questions at the cellular and molecular levels. Here we review the roles of these two metal ions in providing protection against infectious diseases in vivo, and in regulating innate immune responses. In particular, we focus on studies implicating zinc and copper in macrophage antimicrobial pathways, as well as the specific host genes encoding zinc transporters (SLC30A, SLC39A family members) and CTRs (copper transporters, ATP7 family members) that may contribute to pathogen control by these cells

Examining the Latent Structure and Correlates of Sensory Reactivity in Autism: A Multi-Site Integrative Data Analysis by the Autism Sensory Research Consortium

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these supra-modal traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a general response pattern factor for each supra-modal construct and determine the added value of modality-specific response pattern scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ω LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many real-world sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations

In vitro models as tools for screening the relative bioavailabilities of provitamin A carotenoids in foods

This review is organized as follows. First, the characteristics of the digestion and absorption and the metabolism of vitamin A and carotenoids are briefly discussed in Sections 2 and 3, respectively. The numerous factors that affect carotenoid bioavailability are considered in Section 4. Section 5 first presents an overview of the techniques used to determine the relative bioavailabilities of carotenoids in vivo, and then describes the biochemical and cellular methods that are used to investigate the gastrointestinal processes associated with the accessibility and cellular transport of carotenoids. Key results from studies employing in vitro methods are systematically reviewed in Section 6. Finally Section 7 directly compares the findings of in vivo and in vitro studies and, on the basis of this comparison, proposes the use of simulated digestion and Caco-2 cells as tools for the initial screening for the relative bioavailability of provitamin A carotenoids from staple foods prepared according to local methods.PRIFPRI2; HarvestPlusHarvestPlu

Retention during processing and bioaccessibility of β-carotene in high β-carotene transgenic cassava root

PRIFPRI3; ISI; HarvestPlus; CRP4HarvestPlus; A4NHCGIAR Research Program on Agriculture for Nutrition and Health (A4NH

Biological Activities and Bioavailability of Mangosteen Xanthones: A Critical Review of the Current Evidence

Mangosteen (Garcinia mangostana L.) is a tropical tree native to Southeast Asia that produces a fruit whose pericarp contains a family of tricyclic isoprenylated polyphenols referred to as xanthones. Numerous in vitro studies have shown that these xanthones possess anti-oxidant, anti-proliferative, pro-apoptotic, anti-inflammatory and anti-carcinogenic activities. Aggressive marketing of such health promoting benefits has resulted in mangosteen’s classification as a “superfruit”. This has led to sales of mangosteen containing beverages in USA alone exceeding $200 million in 2008 despite very limited animal and human studies. This review will (a) critically address recent reports of in vivo studies on the bioavailability and metabolism of mangosteen xanthones, (b) update the in vitro and in vivo data on anti-cancer and anti-inflammatory activities of mangosteen xanthones, and (c) suggest needed areas of inquiry regarding the absorption, metabolism and efficacy of mangosteen xanthones

Human Lipoproteine as a Vehicle for the Delivery of β-Carotene and α-Tocopherol to HepG2 Cells\u3csup\u3e1\u3c/sup\u3e

Highly differentiated human cell lines represent a useful in vitro model for the study of carotenoid uptake, metabolism, and function. Carotenoids are usually introduced into tissue culture media either in organic solvents or as micelles, whereas carotenoids are localized in lipoproteins in vivo. Initially, the stability of β-carotene and α-tocopherol in micelles and human lipoproteins under standard tissue culture conditions was compared. Recovery of β-carotene and α-tocopherol was 27% ± 2% and 73% ± 2%, respectively, after overnight incubation of micellar β-carotene and α-tocopherol in serum-free medium without cells. This marked loss of β-carotene was attenuated by Inclusion of α-tocopherol in micelles. In contrast, recovery of β-carotene and α-tocopherol was 88%-95% when medium containing the total lipoprotein fraction isolated from β-carotene supplemented individuals was incubated overnight without cells. Cellular accumulation of β-carotene and α-tocopherol from medium containing total lipoproteins (1 mg/ml) was proportional to their concentrations in the lipoprotein fraction (r = 0.94 for β-carotene and 0.74 for α-tocopherol). Cells exhibited similar capability of acquiring β-carotene and α-tocopherol from medium containing either low- or high-density lipoproteins. These data show that lipoproteins represent a stable vehicle for delivery of β-carotein and α-tocopherol to HepG2 human liver cells