Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

We report that daurinol, a novel arylnaphthalene lignan, is a promising potential anticancer agent with adverse effects that are less severe than those of etoposide, a clinical anticancer agent. Despite its potent antitumor activity, clinical use of etoposide is limited because of its adverse effects, including myelosuppression and the development of secondary leukemia. Here, we comprehensively compared the mechanistic differences between daurinol and etoposide because they have similar chemical structures. Etoposide, a topoisomerase II poison, is known to attenuate cancer cell proliferation through the inhibition of DNA synthesis. Etoposide treatment induces G(2)/M arrest, severe DNA damage, and the formation of giant nuclei in HCT116 cells. We hypothesized that the induction of DNA damage and nuclear enlargement due to abnormal chromosomal conditions could give rise to genomic instability in both tumor cells and in actively dividing normal cells, resulting in the toxic adverse effects of etoposide. We found that daurinol is a catalytic inhibitor of human topoisomerase IIa, and it induces S-phase arrest through the enhanced expression of cyclins E and A and by activation of the ATM/Chk/Cdc25A pathway in HCT116 cells. However, daurinol treatment did not cause DNA damage or nuclear enlargement in vitro. Finally, we confirmed the in vivo antitumor effects and adverse effects of daurinol and etoposide in nude mice xenograft models. Daurinol displayed potent antitumor effects without any significant loss of body weight or changes in hematological parameters, whereas etoposide treatment led to decreased body weight and white blood cell, red blood cell, and hemoglobin concentration.

This study investigated the effects of youngiaside A (YA), youngiaside C (YC), and Youngia denticulatum extract (YDE) on extrinsic aging and assessed its molecular mechanisms in UVB-irradiated HaCaT keratinocytes and human dermal fibroblasts (HDFs). The results showed that YA, YC, and YDE decreased matrix metalloproteinase (MMP) expression and production in HaCaT cell and HDFs and increased collagen expression and production in HDFs. In addition, YA, YC, and YDE significantly increased antioxidant enzyme expression, thereby down-regulating UVB-induced reactive oxygen species (ROS) production and ROS-induced mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) signaling in HaCaT cells. Furthermore, YA, YC, and YDE reduced phosphorylation of IκBα and IKKα/β, blocked nuclear factor-κB (NF-κB) p65 nuclear translocation, and strongly suppressed pro-inflammatory mediators. Finally, YA, YC, and YDE augmented UVB-induced adenosine monophosphate activated protein kinase (AMPK) phosphorylation and YA and YC did not inhibit MMP-1 production in AMPK inhibitor or nuclear factor-erythroid 2-related factor-2 (Nrf2) siRNA-treated HaCaT cells. The results suggest that these compounds could be potential therapeutic agents for prevention and treatment of skin photoaging.

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Tectorigenin (Tg) and tectoridin (Td) are the major compounds isolated from the rhizomes of iridaceous plant Belamcanda chinensis which is well known as a chinese traditional medicine for the treatment of inflammatory diseases. In this study we investigated whether tectorigenin and tectoridin can be applied to the suppression of interferon-gamma and lipopolysaccharide (IFN-gamma/LPS)-induced inflammatory responses in macrophages. Anti-inflammatory activities of tectorigenin and tectoridin were compared with genistein (Ge), well known isoflavonoid as a phytoestrogen and regarded as an emerging anti-inflammatory agent. Both compounds showed low cytotoxic effect. In Raw 264.7 cells activated with IFN-gamma/LPS, pre-treated tectorigenin was found to inhibit the expression of inducible nitric oxide synthase (iNOS), the production of nitric oxide (NO) and the secretion of interleukin (IL)-1beta dose-dependently. Tectorigenin also decreased the expression of cyclooxigenase (COX)-2 and the production of prostaglandin E(2) (PGE(2)) in dose-dependent manner. These inhibitory effects of tectorigenin were found to be caused by the blocking of nuclear factor kappa-B (NF-kappaB) activation. Compared with genistein and tectoridin, tectorigenin showed significant inhibitory effect for almost anti-inflammatory tests in this study. All these results clearly demonstrated that tectorigenin appears to have the potential to prevent inflammation.

Before edible insects may be used as an alternative food, it is necessary to develop basic product forms and evaluate their characteristics. We made two basic commercial products (defatted powder and oil) from mealworm, a popular edible insect. The defatted mealworm powder possessed a sufficient amount of protein, and it had a savory taste due to plentiful free amino acids. Additionally, it had abundant minor nutrients and bioactive compounds. The physicochemical properties of mealworm oil were very similar to vegetable oil, and mealworm oil was also abundant in bioactive nutrients, especially γ-tocopherol. In addition, the predicted shelf life of mealworm oil was suitable for commercial use. Moreover, mealworm had high antioxidant and anti-inflammation activities, which may arise from functional peptides and glucosamine derivatives such as chitin and chitosan. In short, the defatted mealworm powder and mealworm oil could be successfully used as novel food ingredients.

The antioxidant properties and phenolic profiles were first investigated in this paper on the leaves of three red pepper cultivars, Blackcuban (BCPL), Hongjinju (HPL), and Yeokgang-hongjanggun (YHPL). Of the ethanol extract of the three cultivars, BCPL showed potent antioxidant activities against the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. Nine antioxidative compounds from the red pepper leaves were isolated and identified as one polyamine phenolic conjugate, N-caffeoylputrescine (1); three chlorogenic acid derivatives, 5-O-caffeoylquinic acid (2), 5-O-caffeoylquinic acid methyl ester (4), and 5-O-caffeoylquinic acid butyl ester (9); one anthocyanin, delphinidin-3-[4-trans-coumaroyl-l-rhamnosyl(1→6)glucopyranoside]-5-O-glucopyranoside (3); and four flavone glycosides, luteolin-7-O-apiofuranosyl(1→2)glucopyranoside (5), luteolin-7-O-glucopyranoside (6), apigenin 7-O-apiofuranosyl(1→2)glucopyranoside (7), apigenin-7-O-glucopyranoside (8). 1 and 3 had the greatest potential for radical-scavenging activity and HepG2 cells protecting effect against oxidative stress. BCPL exhibited the highest content of 1 and 3. Of the three cultivars BCPL may be considered a good source of antioxidants.