Search

Accumulating epidemiological evidence suggests that anthocyanin intake is associated with reduced risks of cardiometabolic disorders, highlighting the importance of incorporating the phytochemical in our diets. Numerous food-based intervention studies have examined, in controlled meal settings, the role of anthocyanin on cardiometabolic health; but their effects have not been systematically summarized. This study aims to systematically review and summarize the effects of anthocyanin consumption with composite meals on cardiometabolic health from randomized controlled feeding trials. A systematic literature search for relevant human nutritional intervention studies was performed using PubMed, Embase, Cochrane Library, CINAHL Plus with Full Text, and Scopus databases. The Cochrane Risk of Bias tool was used to assess the study quality. Eighteen articles involving 371 participants were included in this review. Consistent improvements from anthocyanin intake were found in glycemic, gastric inhibitory peptide (GIP), interleukin-6 (IL-6), and oxygen radical absorbance capacity (ORAC) responses. Anthocyanin intake did not significantly affect other markers of energy metabolism, vascular functions, oxidative stress and antioxidant status, as well as inflammatory responses. Inconsistencies in successful outcomes between epidemiological studies and included interventions were largely attributed to matrix effects, which may impede the bioaccessibility of anthocyanins and consequently, limiting its health benefits when co-delivered with some foods.

Novel staple foods are staple foods that are modified with the purpose of improving their nutritional properties. However, consumers' acceptance towards novel staple foods remains to be evaluated, especially in Asian populations where staple foods like white rice are a major source of energy. The objective of this study was to explore consumers' attitudes and perceptions towards novel staple foods in a multi-ethnic Asian population. We conducted 11 focus group discussions, with 37 healthy participants and 22 participants with diabetes recruited through newspaper, email and poster advertisement and in-person recruitment at a clinic. Thematic analysis using the general inductive approach was performed. We found that participants' conceptual understanding of the modification process affected their acceptance towards novel staple foods. Plant-based modifications were considered natural and acceptable while genetic modification and use of chemicals were unnatural and undesirable. Participants expected novel staple foods to be more expensive and less tasty and this was largely due to their perceptions and experiences with healthy eating. Participants with diabetes or family history of diabetes were generally more willing to compromise taste and cost for healthier staple foods, and this appeared to be driven by concerns about diabetes and its related co-morbidities. The appearance of food was an important influence on participants' initial impression of the food, which appeared to be mediated by taste expectations. Participants’ trust of novel staple foods was largely influenced by their trust in food industry, governmental authorities and nutrition science that was mediated through pathways of information and food safety.

Background Para-coumaric acid methyl ester (pCAME) is one of the bioactive components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin diseases. Purpose To investigate the anti-angiogenic activity of pCAME and its molecular mechanism of action. Study design We investigated the anti-angiogenic activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo. Methods In vitro cell proliferation, would healing, migration and tube formation assays were used, along with in vivo physiological angiogenic vessel formation, tumor-induced angiogenic vessel formation assays on zebrafish model. qRT-PCR and RNA-seq were also used for the target investigation. Results pCAME could inhibit the proliferation, would healing, migration and tube formation of HUVECs, disrupt the physiological formation of intersegmental vessels (ISVs) and the subintestinal vessels (SIVs) of zebrafish embryos, and inhibit tumor angiogenesis in the zebrafish cell-line derived xenograft (zCDX) model of SGC-7901 in a dose-dependent manner. Mechanistic studies revealed that pCAME inhibited vegf/vegfr2 and ang/tie signaling pathways in zebrafish by quantitative RT-PCR analysis, and regulated multi-signaling pathways involving immune, inflammation and angiogenesis in SGC-7901 zCDX model by RNA-seq analysis. Conclusion pCAME may be a multi-target anti-angiogenic drug candidate and hold great potential for developing novel therapeutic strategy for cancer treatment.

The aberrant activities of transcription factors such as the androgen receptor (AR) underpin prostate cancer development. While the AR cis-regulation has been extensively studied in prostate cancer, information pertaining to the spatial architecture of the AR transcriptional circuitry remains limited. In this paper, we propose a novel framework to profile long-range chromatin interactions associated with AR and its collaborative transcription factor, erythroblast transformation-specific related gene (ERG), using chromatin interaction analysis by paired-end tag (ChIA-PET). We identified ERG-associated long-range chromatin interactions as a cooperative component in the AR-associated chromatin interactome, acting in concert to achieve coordinated regulation of a subset of AR target genes. Through multifaceted functional data analysis, we found that AR-ERG interaction hub regions are characterized by distinct functional signatures, including bidirectional transcription and cotranscription factor binding. In addition, cancer-associated long noncoding RNAs were found to be connected near protein-coding genes through AR-ERG looping. Finally, we found strong enrichment of prostate cancer genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) at AR-ERG co-binding sites participating in chromatin interactions and gene regulation, suggesting GWAS target genes identified from chromatin looping data provide more biologically relevant findings than using the nearest gene approach. Taken together, our results revealed an AR-ERG-centric higher-order chromatin structure that drives coordinated gene expression in prostate cancer progression and the identification of potential target genes for therapeutic intervention.

Estrogen induces the binding of ERα to thousands of locations in the breast cancer genome, preferring intergenic and distal regions rather than near the promoters of estrogen-regulated genes. With recent technological innovations in mapping and characterization of global chromatin organization, evidence now indicates ERα mediates long-range chromatin interactions to control gene transcription. The principles that govern how ERα communicates with their putative target genes via chromosomal interactions are also beginning to unravel. Herein, we summarize our current knowledge on the functional significance of chromatin looping in estrogen-mediated transcription. ERα collaborative factors and other players that contribute to define the genomic interactions in breast cancer cells will also be discussed. Defects in chromatin organization are emerging key players in diseases such as cancer, thus understanding how ERα-mediated chromatin looping affects genome organization will clarify the receptor's role in estrogen responsive pathways sensitive to defects in chromatin organization.

The purposes of this study were to examine the effects of different distances and the inclusion and exclusion of acceleration and deceleration distances on the measurement of self-paced and fastest gait speeds in younger and older adults. The self-paced and fastest gait speeds of younger and older adults were measured over 4-m and 10-m walkways with the acceleration and deceleration distances included and excluded in the measuring distance. The results indicated gait speeds (both self-paced and fastest) measured over different distances were comparable only if a distance for acceleration and deceleration was excluded from the measuring distance to obtain stable and comparable gait speeds. Similar results were found for younger and older groups.

Intrarater reliability and measurement error associated with waist and hip circumference measures performed by a novice rater with one measurement were examined and compared among Body Mass Index (BMI) subgroups in a convenience sample of 76 participants (25 men, 51 women; M age = 47.2 yr., SD = 14.2). A rater blinded to the purpose of the study, as well as to the tape measure results, received training and then performed hip and waist circumference measures twice with a 10-min. interval. Intrarater reliability of the measures was acceptable (ICC3,1 >.95) across the BMI subgroups; measurement error was found to be greater in the overweight and obese subgroups. If a test-retest change score is greater than 3.0 cm in waist circumference and 2.0 cm in hip circumference, it can be assumed to be a true change with 95% confidence.

Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor α (ER-α) in the human genome. We found that most high-confidence remote ER-α-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-α functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes. © 2009 Macmillan Publishers Limited. All rights reserved.

Nuclear signaling by estrogens rapidly induces the global recruitment of estrogen receptors (ERs) to thousands of highly specific locations in the genome. Here, we have examined whether ER binding sites that are located distal from the transcription start sites of estrogen target genes are functionally relevant. Similar to ER binding sites near the proximal promoter region, ER binding sites located at distal locations are occupied by ERs after estrogen stimulation. And, like proximal bound ERs, ERs occupied at distal sites can recruit coactivators and the RNA polymerase transcription machinery and mediate specific structural changes to chromatin. Furthermore, ERs occupied at the distal sites are capable of communicating with ERs bound at the promoter region, possibly via long range chromosome looping. In functional analysis, disruption of the response elements in the distal ER binding sites abrogated ER binding and significantly reduced transcriptional response. Finally, sequence comparison of the response elements at the distal sites suggests a high level of conservation across different species. Together, our data indicate that distal ER binding sites are bona fide transcriptional enhancers that are involved in long range chromosomal interaction, transcription complex formation, and distinct structural modifications of chromatin across large genomic spans.

Location analysis for estrogen receptor-alpha (ERalpha)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERalpha-bound loci and quantify the incidence of ERE sequences under two stringencies of detection

Polymorphisms in peroxisome proliferator-activated receptor isoforms may be among the most important single-gene contributors to dyslipidemias, insulin resistance, and maturity-onset diabetes.Familial partial lipodystrophy is a rare but characteristic phenotype associated with carriers of peroxisome proliferator-activated receptor-gamma missense mutations. Mutant receptors are transcriptionally defective, exhibit aberrant affinity for co-regulator molecules, and can exert dominant-negative or haplo-insufficiency effects on normal peroxisome proliferator-activated receptor-gamma function. The P12A variant of isoform gamma is estimated to reduce diabetes risk by 19% in many populations, and has a large attributable risk because of high prevalence of the normal allele. Variants L162V and V227A of isoform alpha (common in white and Oriental populations, respectively) are associated with sexually dimorphic perturbations of lipid metabolism and cardiovascular risk. Polymorphisms in isoforms alpha and beta/delta are reported to influence lipid and glucose utilization. Apart from lipodystrophic syndromes, metabolic and cardiovascular risk in peroxisome proliferator-activated receptor variants is apparently modulated by dietary and exercise interventions, and interactions with polymorphisms in other genetic loci.Polymorphisms in peroxisome proliferator-activated receptors are critical susceptibility risk factors for dyslipidemias and diabetes. They provide attractive targets for gene-environment interventions to reduce the burden of metabolic disease.

Peroxisome proliferator-activated receptor-α (PPARα) is a central regulator of lipid metabolism. Fibrate drugs act on PPARα to modulate dyslipidemias. A natural variant (V227A) affecting the PPARα hinge region was associated with perturbations in blood lipid levels in Asian populations. In this study, we investigated the functional significance of the V227A substitution. The variant significantly attenuated PPARα-mediated transactivation of the cytochrome P450 4A6 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) genes in the presence of fibrate ligands. Screening of a panel of PPARα coregulators revealed that V227A enhanced recruitment of the nuclear corepressor NCoR. Transactivation activity of V227A could be restored by silencing NCoR or by inhibition of its histone deacetylase activity. Deletion studies indicated that PPARα interacted with NCoR receptor-interacting domain 1 (ID1) but not ID2 or ID3. These interactions were dependent on the intact consensus nonapeptide nuclear receptor interaction motif in NCoR ID1 and were enhanced by the adjacent 24 N-terminal residues. Novel corepressor interaction determinants involving PPARα helices 1 and 2 were identified. In hepatic cells, the V227A substitution stabilized PPARα/NCoR interactions and caused defective release of NCoR in the presence of agonists on the HMGCS2 promoter. These results provide the first indication that defective function of a natural PPARα variant was due, at least partially, to increased corepressor binding. Our data suggest that the PPARα/NCoR interaction is physiologically relevant and can produce a discernable phenotype when the magnitude of the interaction is altered by a naturally occurring variation.

Compounds that target the peroxisome proliferator-activated receptors PPARalpha and PPARgamma are used to correct dyslipidemia and to restore glycemic balance, respectively. Because the majority of diabetic patients suffer from atherogenic lipid abnormalities, in addition to insulin resistance, ligands are required that can activate both PPARalpha and PPARgamma. In this study, we used chimeric PPARalpha/gamma reporter-gene bioassays to screen herbal extracts with purported antidiabetic properties. Extracts of Astragalus membranaceus and Pueraria thomsonii significantly activated PPARalpha and PPARgamma. Bioassay-guided fractionation resulted in the isolation of the isoflavones, formononetin, and calycosin from Astragalus membranaceus, and daidzein from Pueraria thomsonii as the PPAR-activating compounds. We investigated the effects of these and 2 common isoflavones, genistein and biochanin A, using chimeric and full-length PPAR constructs in vitro. Biochanin A and formononectin were potent activators of both PPAR receptors (EC50 = 1-4 micromol/L) with PPARalpha/PPARgamma activity ratios of 1:3 in the chimeric and almost 1:1 in the full-length assay, comparable to those observed for synthetic dual PPAR-activating compounds under pharmaceutical development. There was a subtle hierarchy of PPARalpha/gamma activities, indicating that biochanin A, formononetin, and genistein were more potent than calycosin and daidzein in chimeric as well as full-length receptor assays. At low doses, only biochanin A and formononetin, but not genistein, calycosin, or daidzein, activated PPARgamma-driven reporter-gene activity and induced differentiation of 3T3-L1 preadipocytes. Our data suggest the potential value of isoflavones, especially biochanin A and their parent botanicals, as antidiabetic agents and for use in regulating lipid metabolism.