Relationship between Dietary Magnesium, Manganese, and Copper and Metabolic Syndrome Risk in Korean Adults: The Korea National Health and Nutrition Examination Survey (2007–2008)

Recent studies have reported correlations between mineral intake and metabolic syndrome (MS), but accurate relationships and consistency in the results are difficult to confirm. Accordingly, this study aims to assess the dietary intakes of magnesium (Mg), manganese (Mn), and copper (Cu) to determine their relationship with MS. Data from a total of 5,136 adults (2,084 men, 3,052 women) was collected from the 2007–2008 Korea National Health and Nutrition Examination Survey (KNHANES), and the intakes of Mg, Mn, and Cu of the MS patients were compared with those of healthy adults. The relationship between the intakes of these minerals and the MS risks was analyzed. Diagnosis of MS was evaluated by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) standards. Among all study subjects, 25.9 % (540 subjects) of the men and 24.5 % (748 subjects) of the women met diagnostic criteria for inclusion in the MS group. In the men, daily intakes of Mg and Cu in the MS group were significantly lower than those in control group, and in the women, daily intakes of energy, Mg, Mn, and Cu in the MS group were significantly lower than those of the control group. The women subjects with high blood pressure showed significantly lower intakes of Mg, Mn, and Cu than control subjects. In addition, in the women, the highest quartile of Mg and Cu was inversely associated with MS, but with adjustment were not maintained. However, in the postmenopausal women, MS was significant and inversely associated with the highest quartiles of Cu intake and the association remained significant after adjustments. Considering that MS incidence increases and dietary intake and nutrient density decrease with increasing age, and mineral intake is reduced accordingly, these results suggest that meal management with adequate mineral intake is advisable to control MS.     

Evaluation of optimum dietary vitamin E requirements using DL‐α‐tocopheryl acetate in the juvenile eel,Anguilla japonica

The study aimed at evaluating the optimum dietary vitamin E requirements using DL‐α‐tocopheryl acetate in the juvenile eel, Anguilla japonica, as assessed by fish growth performance and fish body composition. Five semi‐purified experimental diets were formulated to contain 0 (TA₁), 15 (TA₁₇), 30 (TA₃₂), 60 (TA₆₂) and 120 (TA₁₁₉ mg TA kg^?1 diet on a dry matter (DM) basis in the form of DL‐α‐tocopheryl acetate (TA). After a 4‐week conditioning period, fish (15 ± 0.3 g) were randomly distributed into aquaria in groups of 20 at 25 ± 1.0°C (mean ± SD). One of the five diets was fed on a DM basis to fish in three randomly selected aquaria twice daily to satiation (approximately 3% of wet body weight per day at the beginning and 2% of wet body weight per day at the end of the feeding trial) for 12 weeks. At the end of the 12‐week feeding trial, weight gain (WG), specific growth rate (SGR), feed efficiency (FE) and protein efficiency ratio (PER) were determined; these were significantly lower in control fish than in fish fed supplemented diets (P < 0.05). The values for fish fed TA₁₇ were significantly higher than for fish fed TA₁, TA₆₂ or TA₁₁₉ (P < 0.05). There were no significant differences in WG, FE or PER among fish that were fed TA₁₇ and TA₃₂, among those that were fed TA₃₂ and TA₆₂, and among those that were fed TA₆₂ and TA₁₁₉ (P > 0.05). There were also no significant differences in SGR among fish fed TA₃₂, TA₆₂ or TA₁₁₉ (P > 0.05). A broken‐line regression analysis on the basis of WG, SGR, FE and PER showed that dietary vitamin E requirements of juvenile eels were 21.2, 21.6, 21.2 and 21.5 (mg kg^?1 diet), respectively. These results indicate that the dietary vitamin E requirement could be <21.2 mg kg^?1 but <21.6 mg kg^?1 diet in juvenile eel, A. japonica, when DL‐α‐tocopheryl acetate is used as the dietary vitamin E source.     

Genetic analysis of auditory neuropathy spectrum disorder in the Korean population

Auditory neuropathy spectrum disorder (ANSD) is caused by dys-synchronous auditory neural response as a result of impairment of the functions of the auditory nerve or inner hair cells, or synapses between inner hair cells and the auditory nerve. To identify a causative gene causing ANSD in the Korean population, we conducted gene screening of the OTOF, DIAPH3, and PJVK genes in 19 unrelated Korean patients with ANSD. A novel nonsense mutation (p.Y1064X) and a known pathogenic mutation (p.R1939Q) of the OTOF gene were identified in a patient as compound heterozygote. Pedigree analysis for these mutations showed co-segregation of mutation genotype and the disease in the family, and it supported that the p.Y1064X might be a novel genetic cause of autosomal recessive ANSD. A novel missense variant p.K1017R (c.3050A>G) in the DIAPH3 gene was also identified in the heterozygous state. In contrast, no mutation was detected in the PJVK gene. These results indicate that no major causative gene has been reported to date in the Korean population and that pathogenic mutations in undiscovered candidate genes may have an effect on ANSD.     

Contrast in the circadian behaviors of an electrodermal activity and bioimpedance spectroscopy

ABSTRACT

Probing the electrical response of the human body is minimally invasive and a promising area of investigation for future health care. The electrical responses of individuals may vary depending on daily physiological rhythms or environmental changes, which may hamper their prediction for pathological status. In this study, we observed circadian expressions via both alternating current (AC) and direct current (DC) electrical responses of the human body using bioelectrical impedance analysis (BIA) and electrodermal activity (EDA). In total, 14 healthy adults (9 males and 5 females) participated and were hospitalized for 2 nights with controlled caloric intake, sleep hours and residential conditions. The EDA data showed a significant circadian rhythm, but the BIA data did not show significant modulations during the measurement period. No difference was found between circadian changes in male and female participants. The acrophase of the EDA voltage response showed similar behavior with variations in the heart rate variability, with a resistance minimum occurring at approximately 4 pm, implying that the behavior of the EDA is probably affected by the sympathetic nerve response. Moreover, the resistance of the EDA varied by up to 15% from its mean value, which suggests that circadian variations cannot be neglected for the correct diagnosis of pathological conditions. In contrast, the BIA method did not show this circadian variation but showed independent results over the measurement period. This difference in performance implies that the DC and AC responses of the human body contain different electrophysiological information.     

Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors

Holoprosencephaly (HPE), a common human congenital anomaly defined by a failure to delineate the midline of the forebrain and/or midface, is associated with diminished Sonic hedgehog (SHH)-pathway activity in development of these structures. SHH signaling is regulated by a network of ligand-binding factors, including the primary receptor PTCH1 and the putative coreceptors, CDON (also called CDO), BOC, and GAS1. Although binding of SHH to these receptors promotes pathway activity, it is not known whether interactions between these receptors are important. We report here identification of missense CDON mutations in human HPE. These mutations diminish CDON's ability to support SHH-dependent gene expression in cell-based signaling assays. The mutations occur outside the SHH-binding domain of CDON, and the encoded variant CDON proteins do not display defects in binding to SHH. In contrast, wild-type CDON associates with PTCH1 and GAS1, but the variants do so inefficiently, in a manner that parallels their activity in cell-based assays. Our findings argue that CDON must associate with both ligand and other hedgehog-receptor components, particularly PTCH1, for signaling to occur and that disruption of the latter interactions is a mechanism of HPE.     

SUMO1 attenuates stress-induced ROS generation by inhibiting NADPH oxidase 2

Small ubiquitin-like modifier 1 (SUMO1) is a member of the superfamily of ubiquitin-like proteins. Despite its structural similarity with ubiquitin, SUMO1 does not seem to play any role in protein degradation and its precise biological function is poorly understood. During our studies on heat-shock responses, we found that heat-shock stress increased SUMO1 conjugation in a dose-dependent manner. Intriguingly, SUMO1 conjugation resulted in decrease of intracellular ROS generation and protection cells from death under heat-shock stress. We showed that NADPH oxidase 2 (NOX2) is a target protein of sumoylation by SUMO1 using immunoprecipitation and is colocalized with SUMO1 at plasma membrane. Additionally, we demonstrated that the attenuation in intracellular ROS generation resulted from inhibition of NADPH oxidase complex (NOX) activity. These results suggested that SUMO1 plays an important role in modulation of NOX activity required for ROS generation.     

Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-α-induced NF-κB activity by binding to TNFR1

IGFBP-5 is known to be involved in various cell phenomena such as proliferation, differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-α, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-κB activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-α in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-α resulted in inhibition of TNF-α-induced NF-κΒ activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-α inhibitor.     

Novel factor Xa inhibitor,maslinic acid,with antiplatelet aggregation activity

As antithrombotic effects of maslinic acid (MA) have not yet been studied, MA-mediated downregulation of coagulation factor Xa (FXa) and platelet aggregation was studied. We show that MA inhibited the enzymatic activity of FXa and platelet aggregation, induced by adenosine diphosphate (ADP) and a thromboxane A₂ (TXA₂) analog, U46619 with a similar antithrombotic efficacy to rivaroxaban, a direct FXa inhibitor used as a positive control. Mechanistically, MA suppressed U46619- or ADP-induced phosphorylation of myristoylated alanine-rich C kinase substrate, and the expression of P-selectin, and activated PAC-1 in platelets. MA increased generation of nitric oxide, but downregulated excessive secretion of endothelin-1 in ADP- or U46619-treated human umbilical vein endothelial cells. In arterial and pulmonary thrombosis mouse model, MA showed prominent anticoagulant and antithrombotic effects. Our data suggest MA as a candidate molecule for a new class of drugs targeting anti-FXa and antiplatelet.     

Design,Synthesis and Bioevaluation of Two Series of 3‐[(1‐Benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐ones and N‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines

Two series of 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐ones and N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 % in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC‐3 (prostate cancer), and NCI?H23 (lung cancer), with 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one being the most cytotoxic agent. 3‐[(1‐Benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines could serve as new leads for further design and AChE inhibitors, while 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one could serve as a new lead for the design and development of more potent anticancer agents.