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Since arginase has been shown to compete with nitric oxide (NO) synthase, emerging evidence has reported that arginase inhibition improves obesity by increasing NO production. Semen cuscutae (SC), which is a well-known Chinese medicine, has multiple biological functions such as anti-oxidant function and immune regulation. In this study, we investigated whether the SC as a natural arginase inhibitor influences hepatic lipid abnormalities and whole-body adiposity in high-fat diet (HFD)-induced obese mice. The lipid accumulation was significantly reduced by SC treatment in oleic acid-induced hepatic steatosis in vitro. Additionally, SC supplementation substantially lowered HFD-induced increases in arginase activity and weights of liver and visceral fat tissue, while increasing hepatic NO. Furthermore, elevated mRNA expressions of sterol regulatory element-binding transcription factor 1 (SREBP-1c), fatty-acid synthase (FAS), peroxisome proliferator-activated receptor-gamma (PPAR-&gamma, )1, and PPAR-&gamma, 2 in HFD-fed mice were significantly attenuated by SC supplementation. Taken together, SC, as a novel natural arginase inhibitor, showed anti-obesity properties by modulating hepatic arginase and NO production and metabolic pathways related to hepatic triglyceride (TG) metabolism.

We have synthesised mono-(NpCb) and bis-[(N,N-phenyl-1-naphthylamino)benzo]-o-caboranes (NpCbNp), which show anomalously intense aggregation-induced emission (AIE) at long wavelengths and monomer emission at short wavelengths. The actual concentration of the aggregator in intense AIE is very low, so absorption spectroscopy is unsuitable for detecting small changes in the absorbance. Hence, to understand the aggregation pattern, we employ excitation spectroscopy, since this method has excellent sensitivity in compliance with the emission intensity. Moreover, we carried out synchronous fluorescence spectroscopic measurements to confirm that the aggregator is different from the monomeric species. The excitation spectrum shows distinguishable differences between the AIE and the normal emission. For the triad NpCbNp, the excitation spectrum for the AIE is located at a shorter wavelength than that for the monomeric emission spectrum, which means that the AIE is attributed to the H-type aggregator. On the other hand, for the dyad NpCb, the excitation spectrum for the AIE is observed at an identical wavelength as that for the monomeric species, which indicates that the aggregator is of the oblique type.

We report the results of photoinduced electron transfer (PET) in a novel dyad, in which a boron dipyrromethene (BODIPY) dye is covalently linked to o-carborane (o-Cb). In this dyad, BODIPY and o-Cb act as electron donor and acceptor, respectively. PET dynamics were investigated using a femtosecond time-resolved transient absorption spectroscopic method. The free energy dependence of PET in the S1 and S2 states was examined on the basis of Marcus theory. PET in the S1 state occurs in the Marcus normal region. Rates are strongly influenced by the driving force (−ΔG), which is controlled by solvent polarity; thus, PET in the S1 state is faster in polar solvents than in nonpolar ones. However, PET does not occur from the higher energy S2 state despite large endothermic ΔG values, because deactivation via internal conversion is much faster than PET.

Accumulation of α-Synuclein (α-Syn) causes Parkinson's disease (PD) as well as other synucleopathies. α-Syn is the major component of Lewy bodies and Lewy neurites, the proteinaceous aggregates that are a hallmark of sporadic PD. In familial forms of PD, mutations or copy number variations inSNCA(the α-Syn gene) result in a net increase of its protein levels. Furthermore, common risk variants tied to PD are associated with small increases ofwild-typeα-Syn levels. These findings are further bolstered by animal studies which show that overexpression of α-Syn is sufficient to cause PD-like features. Thus, increased α-Syn levels are intrinsically tied to PD pathogenesis and underscore the importance of identifying the factors that regulate its levels. In this study, we establish a pooled RNAi screening approach and validation pipeline to probe the druggable genome for modifiers of α-Syn levels and identify 60 promising targets. Using a cross-species, tiered validation approach, we validate six strong candidates that modulate α-Syn levels and toxicity in cell lines,Drosophila, human neurons, and mouse brain of both sexes. More broadly, this genetic strategy and validation pipeline can be applied for the identification of therapeutic targets for disorders driven by dosage-sensitive proteins.SIGNIFICANCE STATEMENTWe present a research strategy for the systematic identification and validation of genes modulating the levels of α-Synuclein, a protein involved in Parkinson's disease. A cell-based screen of the druggable genome (>7,500 genes that are potential therapeutic targets) yielded many modulators of α-Synuclein that were subsequently confirmed and validated inDrosophila, human neurons, and mouse brain. This approach has broad applicability to the multitude of neurological diseases that are caused by mutations in genes whose dosage is critical for brain function.

Obesity is a serious health problem which may continuously increase the morbidity and mortality associated with a variety of acute and chronic diseases.This study aimed to examine the antiobesity effect of soy bean extract fermented by Bacillus subtilis MORI (BTD-1) and to elucidate the mechanisms underlying such effects using 3T3-L1 preadipocytes. Lipid accumulations were significantly inhibited by BTD-1 treatment, which were accompanied by the decreased expression of CCAAT element binding protein α (C/EBPα) and the increased phosphorylation of acetyl-CoA carboxylase (ACC) protein expression. In addition, BTD-1 treatment increased the expression of glucose transporter 4 (GLUT4) along with significantly increasing glucose uptake into the adipocytes based on results of a 2-deoxy-D-[3H] glucose uptake assay. Our findings suggest that BTD-1 may suppress the differentiation of 3T3-L1 adipocytes and greatly facilitate glucose uptake into the adipocytes. Therefore, BTD-1 has a potential as a functional food ingredient in improving obesity and related metabolic disorders.

Electron donor-acceptor (D-A) systems with a triphenylamino moiety (D) and ortho-carborane (A) show three kinds of intriguing emissions that can be attributed to the local excited state, the intramolecular charge-transfer state, and the aggregation-induced emission state. The emission behaviors depend on which positions of the carborane are substituted.

Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

Upregulated arginase activity, which competes with nitric oxide synthase (NOS), impairs nitric oxide production and has been implicated in various metabolic disorders. This study examined whether circulating amino acid metabolite ratios are associated with arginase and NOS activities and whether arginine bioavailability is associated with metabolic syndrome (MetS). Data related to arginase and NOS activities were collected from non-diabetic Koreans without cardiovascular disease (n = 1998) in the Ansan–Ansung cohorts (2005–2006). Subsequently, correlation and multivariate logistic regression analyses were performed. With the increase in the number of MetS risk factors, ratios of circulating amino acid metabolites, such as those of ornithine/citrulline, proline/citrulline, and ornithine/arginine, also significantly increased, whereas arginine bioavailability significantly decreased. These metabolite ratios and arginase bioavailability were also significantly correlated with MetS risk-related parameters, which remained significant after adjusting for covariates. In addition, logistic regression analysis revealed that high ratios of circulating metabolites and low arginine bioavailability, which indicated increased arginase activity, were significantly associated with a high MetS risk. This study demonstrated that altered ratios of circulating amino acid metabolites indicates increased arginase activity and decreased arginine bioavailability, both of which can be potential markers for MetS risk.

Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2 alpha (p-eIF2 alpha), ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

In order to understand the causes of the emission shape and colour changes of heteroleptic Ir3+ complexes containing 2-(2,4-difluorophenyl)pyridine (dfppy) as the main ligands, we introduced two types of ancillary ligands: (1) non-luminescent ancillary ligands, namely tetrakis(pyrazolyl)borate (bor) and picolinate (pic), which were employed for the preparation of Ir(dfppy)2(bor) and Ir(dfppy)2(pic), respectively, and (2) luminescent ancillary ligands, namely 1,10-phenanthroline (phen), bipyridine (bpy), and 2,3-dipyridylpyrazine (dpp), which were employed for the preparation of Ir(dfppy)2(phen), Ir(dfppy)2(bpy), and Ir(dfppy)2(dpp), respectively. In a glassy matrix at 77 K, the Ir complexes showed well-structured emission spectra, except Ir(dfppy)2(dpp). The vibronic structures in the emission spectra of Ir(dfppy)2(bor) and Ir(dfppy)2(pic) were maintained even at 300 K. However, Ir(dfppy)2(phen), Ir(dfppy)2(bpy), and Ir(dfppy)2(dpp) showed markedly red-shifted and broad emission spectra. The anomalous rigidochromism was attributed to an interligand energy transfer (ILET), and showed a strong temperature dependence. The excited states of dfppy are higher than those of phen, bpy, and dpp; thus, ILET occurs from dfppy to the other ligands lying in lower energy states. The ILET dynamics were probed directly using femtosecond transient absorption (TA) spectroscopy after the excitation of dfppy. As the time delay increased, the intensity of the TA band of dfppy decreased, while those of the bands related to the phen, bpy, and dpp ancillary ligands increased. On the other hand, no changes in the TA spectra were observed for Ir(dfppy)2(bor) and Ir(dfppy)2(pic). The TA spectral behaviours can be explained in terms of the relative ordering of the emissive states for cyclometalating and ancillary ligands.

Circulating neutrophil gelatinase-associated lipocalin (NGAL) is associated with obesity-related metabolic disorders. This study investigated the relationship between serum NGAL and early alteration of metabolic parameters in non-diabetic Korean women, particularly with respect to saturated fat (SFA) intake. Anthropometric parameters, fasting glycemic status, and levels of lipids, oxidative stress/inflammatory markers, and NGAL were measured in 82 non-diabetic Korean women [Super-healthy group (n=57) with 0 metabolic syndrome risk factor (MetS RF) and MetS-risk group (n=25) with MetS RF≥1]. Age, weight, waist circumference, blood pressure, fasting glucose, HbA1C, triglyceride, LDL and total-cholesterol, and NGAL levels were higher, and HDL-cholesterol was lower in the MetS-risk group than in the Super-healthy group. Age-adjusted serum NGAL levels were higher in the MetS-risk group than in the Super-healthy group. NGAL increased proportionally with increase in MetS RFs (p=0.038) and correlated positively with BMI, triglycerides, LDL- and total-cholesterol, interleukin-6, white blood cell count, and neutrophil%, and negatively with HDL-cholesterol and superoxide dismutase activity. Serum NGAL levels positively correlated with SFA intake before and after adjustment (age and BMI). Serum NGAL levels were higher in high-SFA consumers [≥7g/day, ≥7% of total calorie intake (TCI)] than in low-SFA consumers (

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor-α), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

Adiponectin, an adipokine, has been described as showing physiological benefits against obesity-related malfunctions and vascular dysfunction. Several natural compounds that promote the expression and secretion of adipokines in adipocytes could be useful for treating metabolic disorders. This study investigated the effect of fisetin, a dietary flavonoid, on the regulation of adiponectin in adipocytes using 3T3-L1 preadipocytes. The expression and secretion of adiponectin increased in 3T3-L1 cells upon treatment with fisetin in a dose-dependent manner. Fisetin-induced adiponectin secretion was inhibited by peroxisome proliferator-activated receptor (PPAR) antagonists. It was also revealed that fisetin increased the activities of PPARs and silent mating type information regulation 2 homologue 1 (SIRT1) in a dose-dependent manner. Furthermore, the up-regulation of adiponectin and the activation of PPARs induced by fisetin were prevented by a SIRT1 inhibitor. Fisetin also promoted deacetylation of PPAR γ coactivator 1 (PGC-1) and its interaction with PPARs. SIRT knockdown by siRNA significantly decreased both adiponectin production and PPARs-PGC-1 interaction. These results provide evidence that fisetin promotes the gene expression of adiponectin through the activation of SIRT1 and PPARs in adipocytes.

We investigated plasma metabolite profiles that correlated with age-related serum alanine aminotransferase (ALT) levels. The study included 602 healthy, nondiabetic subjects (aged 30-65 years); 393 individuals had normal ALT levels at baseline. Fifty-three (13.5%) individuals developed elevated ALT levels after 3 years. The remaining 340 subjects with normal ALT were matched to the elevated-ALT group (n = 53) for age, gender, BMI, fasting glucose, and ALT to form the control group (n = 53). At the 3-year follow-up, the elevated-ALT group exhibited greater increases in waist circumference, serum free fatty acid, ALT, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), bilirubin, plasma oxidized LDL, Lp-PLA2 activity, urinary 8-epi-prostaglandin F2α (8-epi-PGF2α), and brachial-ankle pulse-wave velocity (ba-PWV) compared to the control group after baseline adjustment. The elevated-ALT group exhibited greater increases in plasma l-valine (q = 0.036), l-leucine (q = 0.012), l-phenylalanine (q = 0.012), and decanoylcarnitine (q = 0.002). Mean ALT levels positively correlated with changes in these four metabolites, which correlated with changes in AST, GGT, Lp-PLA2 activity, urinary 8-epi-PGF2α, and ba-PWV. Mean ALT changes did not significantly correlate with HOMA-insulin resistance. These results suggest that increased plasma levels of l-valine, l-leucine, l-phenylalanine, and decanoylcarnitine precede insulin resistance during periods of elevated ALT. This metabolic disturbance coincides with enhanced risk factors for cardiovascular disease.

Blood or dietary polyunsaturated fatty acids (PUFAs), particularly ω3-PUFAs were known for cardiovascular protective effect. However, the results are still controversial. We aimed to investigate the association of serum phospholipid PUFAs with cardiometabolic risk through cross-sectional/experimental studies.Serum phospholipid FA compositions and cardiometabolic risk parameters were measured in controls [healthy: n=987, metabolic syndrome (MetS): n=214] and CAD patients (CAD-only: n=152, CAD+MetS: n=56). Experimental assays were performed in vascular smooth muscle cells (VSMCs).Major cardiometabolic risk markers, i.e. insulin resistance, hs-C-reactive proteins, and malondialdehyde were higher, and adiponectin and LDL particle size were lower in CAD patients, particularly those with MetS than in healthy controls. Serum linoleic acid (LA, C18:2ω-6) was lowest and dihomo-γ-linolenic acids (DGLAs, C20:3ω-6) were highest in CAD patients with MetS among the 4 groups. Docosahexaenoic acid (DHA, C22:6ω-3) was lower and arachidonic acid (AA, C20:4ω-6) and ω6/ω3-PUFAs were higher in CAD patients than in controls. ω3-PUFAs were significantly lower in CAD patients, particularly those with MetS than in healthy controls. Multiple regression analysis revealed that AA and DHA among serum FAs were mainly associated with the cardiometabolic risk (β'-coefficients for AA:0.336; DHA: -0.296) together with age, MetS factors, LA, DGLA and gender (r=0.529, p0.001). Under LPS-induced stress condition, LA and DHA significantly suppressed VSMC proliferation. DHA also up-regulated the phosphorylation of p38 and ERK, and dramatically inhibited nuclear translocation of NF-κB-p65 in VSMCs.AA and DHA were mainly associated with cardiometabolic risk. Particularly, DHA may be effective on suppression of vascular proliferation and inflammation.

Alzheimer's disease (AD) is associated with an elevated risk for seizures that may be fundamentally connected to cognitive dysfunction. Supporting this link, many mouse models for AD exhibit abnormal electroencephalogram (EEG) activity in addition to the expected neuropathology and cognitive deficits. Here, we used a controllable transgenic system to investigate how network changes develop and are maintained in a model characterized by amyloid β (Aβ) overproduction and progressive amyloid pathology. EEG recordings in tet-off mice overexpressing amyloid precursor protein (APP) from birth display frequent sharp wave discharges (SWDs). Unexpectedly, we found that withholding APP overexpression until adulthood substantially delayed the appearance of epileptiform activity. Together, these findings suggest that juvenile APP overexpression altered cortical development to favor synchronized firing. Regardless of the age at which EEG abnormalities appeared, the phenotype was dependent on continued APP overexpression and abated over several weeks once transgene expression was suppressed. Abnormal EEG discharges were independent of plaque load and could be extinguished without altering deposited amyloid. Selective reduction of Aβ with a γ-secretase inhibitor has no effect on the frequency of SWDs, indicating that another APP fragment or the full-length protein was likely responsible for maintaining EEG abnormalities. Moreover, transgene suppression normalized the ratio of excitatory to inhibitory innervation in the cortex, whereas secretase inhibition did not. Our results suggest that APP overexpression, and not Aβ overproduction, is responsible for EEG abnormalities in our transgenic mice and can be rescued independently of pathology.

Various biologic mediators, including matrix metalloproteinases (MMPs), that are implicated in periodontal tissue breakdown can be induced by cytokines. MMPs are known to degrade periodontal ligament attachment, and bone matrix proteins and tissue inhibitors of metalloproteinase (TIMPs) inhibit the activity of MMPs. The aim of this study is to investigate the effect of tumor necrosis factor (TNF)-α on the expression of MMPs in human periodontal ligament (PDL) cells in vitro and establish which MMPs are expressed specifically in response to that stimulus.Cultured PDL cells were stimulated with TNF-α and analyzed with an MMP antibody array. Real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and western blot with cell lysate and zymography were used to measure messenger RNA (mRNA) and protein levels of MMP-3, -10, and -13. To examine TNF receptor (TNFR) expression, PDL cells were examined by flow cytometry, and expression of MMP-3, -10, and -13 was observed after blocking the TNFR with an antagonist. Results from real-time PCR, ELISA, and western blot were analyzed by paired t test.The antibody array showed that the protein most strongly upregulated by TNF-α stimulation was MMP-3, followed by MMP-13 and MMP-10. The TNF-α receptor blocker specifically inhibited expression of MMP-3 and -13. In addition, TNF-α increased levels of MMP mRNAs in MMP-3, -13, and -10 (in decreasing order). However, ELISAs showed that MMP-13 was the most upregulated protein, followed by MMP-10 and MMP-3. Western blotting indicated that TNF-α increased MMP-3 and -13 levels but had no significant effect on the level of MMP-10, and zymography showed that TNF-α increased the activities of all forms of MMP-3 and -13, but MMP-10 was not detected. Flow cytometry demonstrated that the majority of PDL cells expressed TNFR1.TNF-α (10 ng/mL) upregulates levels of MMP-3, -10, and -13 in human PDL cells. These results suggest that these proteins play an important role in the inflammation of PDLs.

We investigated weight loss effect of personalized diet education in overweight/obese Korean adults. Overweight/obese Korean adults (body mass index [BMI] ≥ 23 kg/m2 or waist circumference [WC] ≥ 90 cm for men, ≥ 85 cm for women) were recruited, and 40 participants who completed the 10-week intervention were finally included in the analyses. At first visit, study participants (small group with individual counseling) were educated for optimal diet by clinical dietitian, and checked for their compliance through telephone/text message every 1–2 week during the intervention. Anthropometric and biochemical parameters and dietary intake were investigated. Body weight, BMI, WC, and body fat mass were significantly reduced in whole participants. Hemoglobin A1c, insulin, and low-density lipoprotein cholesterol were also significantly decreased after the intervention. Total energy intake (EI) during the intervention was not significantly decreased compared to the baseline value, but the proportions of energy derived from macronutrients were within the ranges recommended by 2015 Dietary Reference Intake for Koreans. Based on actual EI, participants were classified into high-adherence (HA) (prescribed EI ± 25%, n = 29), low-adherence I (LA-I) (< 75% of prescribed EI, n = 7), and low-adherence II (LA-II) group (> 125% of prescribed EI, n = 4). Only HA group showed significant improvements in anthropometric parameters, glycemic control and lipid profile. Interestingly, LA-I group showed significant increases in glucose, insulin, C-peptide and insulin resistance. In conclusion, a shift from overweight/obesity to healthy weight can be accomplished by high adherence to personalized diet modification, not by EI reduction.

We investigated the clinical significance of epithelial-mesenchymal transition (EMT) phenotype in 184 small intestinal adenocarcinomas (SIACs) based on the expression pattern of EMT-related proteins in cancer cells.Immunohistochemistry for epithelial (E-cadherin) and mesenchymal (vimentin and fibronectin) markers were performed and cases of SIAC were classified into four subtypes of EMT: complete type (E-cadherin-, vimentin+ and/or fibronectin+), wild type (E-cadherin+, vimentin-, fibronectin-), incomplete 1 type (hybrid type; E-cadherin+, vimentin+ and/or fibronectin+), and incomplete 2 type (null type; E-cadherin-, vimentin-, fibronectin-).We identified 19 (10.3%) cases of complete EMT type, 86 (46.7%) cases of wild type and 79 (43%) cases of incomplete EMT type [hybrid type, 22 (12%) cases; null type, 57 (31%) cases]. Complete EMT phenotype showed a significant association with undifferentiated histology (p0.001). Overall survival of SIAC patients with complete EMT phenotype was significantly shorter than those of patients with incomplete (p=0.001) and wild (p0.001) types. In multivariate analysis, complete EMT phenotype was an independent prognostic factor in SIAC patients (hazard ratio 2.3; 95% confidence interval 1.15-4.6; p=0.019).Complete EMT phenotype stratifies a specific group representing a poor clinical outcome in patients with SIAC.

This paper investigates the real exchange rate behaviour under potential existence of nonlinearity. In order to conduct the nonlinearity test, both linear and non-linear autoregressive unit root tests are applied to four different real exchange rates from mixture of industrialized and developing countries. We found that all countries, there is strong threshold effect while the unit root tests show the mixed results depending on countries. This finding implies standard linear unit root tests turn out biased in favour of random work when the true process is nonlinear mean reversion. When half-lives deviation from equilibrium is calculated, the result is much smaller in threshold autoregressive (TAR) specification than linear model.

Objective: While data on the relationship between fatty acid (FA) composition and the risk for total stroke have accumulated, the association between FA composition and the risk for intracranial atherosclerotic stenosis (ICAS) has never been studied. We compared plasma phospholipid FA composition between non-stroke control and ischemic stroke in Korean population, to discern the FA that distinguishes ICAS from total ischemic stroke patients. Methods: Non-stroke controls (n ¼ 215) and stroke patients (no cerebral atherosclerotic stenosis, NCAS: n ¼ 144 and ICAS: n ¼ 104) were finally included in the analysis. Plasma phospholipid FA compositions were analyzed. Results: Age, coexistence of hypertension/diabetes were significantly different among the groups. Phospholipid FA compositions were significantly different between non-stroke control and ischemic stroke patients, and interestingly, between NCAS and ICAS in stroke patients. Pattern analysis showed that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the u3-polyunsaturated FAs were important FAs in distinguishing NCAS and ICAS in strokes. Particularly, the risk of ICAS was inversely associated with levels of DHA contents in phospholipids (OR: 0.590, 95% CI: 0.350e0.993, p < 0.05), indicating that the risk may be increased at lower levels of DHA contents. Conclusion: DHA and EPA are important FAs for distinguishing NCAS and ICAS in strokes. Additionally, the risk of ICAS was inversely associated with the levels of phospholipid DHA, which indicates that sufficient amounts of DHA in plasma or in diet may reduce the risk of ICAS.

This study investigates the association among metabolic risk factors, inflammatory and oxidative stress markers, and brachial–ankle pulse wave velocity (ba-PWV). We conducted a 3-year longitudinal, observational study of 288 middle-aged adults not meeting the criteria for metabolic syndrome (MetS) at the initial screening. We measured metabolic risk factors, inflammatory and oxidative stress markers, and ba-PWV. Within the 3-year study period, 15.6% (45 out of 288) of participants developed MetS. At the 3-year follow-up, patients were categorized as those with MetS (n = 45) and those without MetS (n = 243). Patients with MetS had significantly unfavorable initial measurements of baseline body mass index (BMI), waist circumference (WC), blood pressure (BP), triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and ba-PWV. After 3 years, participants without MetS showed significant increases in WC, diastolic BP (DBP), total- and low-density lipoprotein (LDL)-cholesterol, malondialdehyde (MDA), oxidized-LDL (ox-LDL), and ba-PWV and a significant decrease in HDL-cholesterol and free fatty acids (FFA). Subjects who developed MetS showed significant increases in BMI, WC, BP, TG, glucose, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), MDA, ox-LDL, and ba-PWV and a significant decrease in HDL-cholesterol. Changes in BMI, WC, BP, TG, HDL-cholesterol, glucose, HOMA-IR index, FFA, C-reactive protein (P = .022), IL-6 (P = .004), leukocyte count (P < .001), MDA (P = .002), ox-LDL (P = .015), and ba-PWV (P = .001) differed significantly between the two groups after adjustment for baseline values. Changes in ba-PWV were positively correlated with the changes in systolic and DBP, total-cholesterol, glucose, leukocyte count, and MDA. The age-related increase in arterial stiffness is greater in the presence of MetS with higher levels of inflammatory and oxidative stress markers.

Stroke leads to a variety of pathophysiological conditions such as ischemic infarct, cerebral inflammation, neuronal damage, cognitive decline, and depression. Many endeavors have been tried to find the therapeutic solutions to attenuate severe neuropathogenesis after stroke. Several studies have reported that a decrease in the neuropeptide regulator 'galanin' is associated with neuronal loss, learning and memory dysfunctions, and depression following a stroke. The present review summarized recent evidences on the function and the therapeutic potential of galanin in post-ischemic stroke to provide a further understanding of galanin's role. Hence, we suggest that galanin needs to be considered as a therapeutic factor in the alleviation of post-stroke pathologies.

Background/Aims: Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. Methods: Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. Results: Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. Conclusions: Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women.

Crowberry, Empetrum nigrum var. japonicum, is widely used in folk medicine and grows naturally in Korea. Although some constituents and biological activity of Korean crowberry have been examined, there is little detailed information available. In this study, we investigated the effects of ethanol extracts of crowberry (EECB) on the inhibition of angiogenesis, both in vitro and in vivo. The effects of EECB were tested on in vitro models of angiogenesis, that is, tube formation and proliferation of human umbilical vein endothelial cells (HUVECs). EECB exhibited significant inhibitory effects on tube formation of HUVECs in a concentration-dependent manner. In addition, crowberry significantly suppressed the proliferation of HUVECs in a concentration-dependent manner. Furthermore, strong antiangiogenic activity of EECB samples was observed in the in vivo assay using chick embryo chorioallantoic membrane (CAM). These results indicate that crowberry may have potential applications in the prevention and treatment of angiogenesis-dependent human diseases.

Carborane-based donor–π–acceptor triads (D–π–A–π–D) bearing triarylamine moieties were synthesised. All the monomeric triads showed a blue-green emission in a dilute solution, which was assigned as an intramolecular charge-transfer (CT) emission. The intramolecular CT emission showed large Stokes shifts at a higher solvent polarity. The intramolecular CT emission further shifted to a longer wavelength with the increase in π-conjugation. Interestingly, a strong red emission was observed in highly concentrated solutions or in the solid state, which was assigned as an aggregation-induced emission (AIE). Moreover, the AIE strongly depended on solvent polarity. A large Stokes shift in AIE was attributed to the strong CT character. The changes in the dipole moment for the AIE state and monomer emission were evaluated using the Lippert–Mataga relationship. The density functional theory calculations showed that the change in electron distribution between the aryl amino group (highest occupied molecular orbital, HOMO) and the carborane moiety (lowest unoccupied molecular orbital, LUMO) indicates the intramolecular CT character, and the emission colour changes were attributed to the HOMO–LUMO energy gap controlled by the π-extension of the phenylene linker. The electrochemical properties such as oxidation and reduction potentials were consistent with theoretical calculation results. The emission properties were affected by two main factors: solvent polarity and solubility.

The purpose of this study was to document the presence of a sublingual gland (SLG) herniating inferiorly through the mylohyoid muscle into the submandibular area. A total of 100 half-heads of 50 adult Korean cadavers were enrolled in this study. The floor of the mouth was dissected from the neck, and mylohyoid muscle patency and position of the sublingual gland were evaluated. Demographic factors of the donor and characteristics of the herniation were evaluated. Herniation was found in 29 (58.0 %) of the 50 cadavers or 42 of the 100 half-heads. Herniation was more frequently observed in females than in males (p = 0.009). However, no laterality was observed. Classifying the location of SLG herniation from the midpoint of the mandible to the hyoid bone into 3 regions, 32 (63 %) of herniations were found in the anterior one-third. No ranula formation was observed. The size and weight of normal glands tended to be larger than those of herniated glands, but no statistical significance was observed. An SLG hernia is a very common condition and is more frequently observed in females. As such, SLG herniation should be considered when a submental neck mass is evaluated.

The rapid pace of neuroscience research demands equally efficient and flexible methods for genetically manipulating and visualizing selected neurons within the rodent brain. The use of viral vectors for gene delivery saves the time and cost of traditional germline transgenesis and offers the versatility of readily available reagents that can be easily customized to meet individual experimental needs. Here, we present a protocol for widespread neuronal transduction based on intraventricular viral injection of the neonatal mouse brain. Injections can be done either free-hand or assisted by a stereotaxic device to produce lifelong expression of virally delivered transgenes.

본 연구는 체지방률이 30% 이상인 폐경 후 비만여성 24명을 대상으로 라인댄스운동이 인슐린저항성지수와 에너지대사조절인자에 미치는 영향을 구명하기 위하여 라인댄스운동을 12주간 실시한 후 운동전과 후의 체조성 및 에너지대사조절인자를 측정하여 비교분석하였다. 본 연구의 결과 운동 후에 라인댄스집단에서 체중, 체지방률, 체질량지수, 허리엉덩이둘레비 및 내장지방면적이 유의하게 감소하였고, 제지방량은 증가하였다. 그렐린 및 고밀도지단백 콜레스테롤(HDL-C)은 유의하게 증가하였고, 렙틴, 인슐린, 글루코스, 인슐린저항성지수(HOMA-IR), 총콜레스테롤(TC), 중성지방(TG), 저밀도지단백 콜레스테롤(LDL-C), 수축기혈압(SBP) 및 이완기혈압(DBP)은 유의하게 감소하였으며, 라인댄스집단의 HOMA-IR에 영향을 미치는 에너지대사조절인자의 회귀분석결과에서 주요요인으로 그렐린, 렙틴, 인슐린 및 글루코스로 나타났다. 이상의 결과에서 지속적이고 규칙적인 라인댄스운동이 폐경 후 비만여성의 체지방 감량으로 인한 에너지대사조절인자의 균형적인 대사를 가져오며 이를 통해 인슐린저항성을 개선시켜 폐경 후 나타날 수 있는 여러 가지 생활습관병을 예방하고 개선하는 데 효과가 있을 것으로 사료된다. 【The purpose of this study was to analyze the effects of line dance exercise on HOMA-IR and energy metabolic factors in postmenopausal obese women. The subjects were 24 obese women composed of the line dance group(n=12) trained for 12-week and the control group(n=12). The variables of body composition, HOMA-IR and energy metabolic factors were measured in all the subjects before and after the 12-week line dance exercise. The results of the study in the line dance group were as follows; The body weight, %fat, BMI, WHR and VFA had significantly decreased, but LBM had increased. The ghrelin, HDL-C had significantly increased, but leptin, insulin, glucose, HOMA-IR, TC, TG, LDL-C, SBP and DBP had decreased. And ghrelin, leptin, insulin, and glucose were the energy metabolic factors affecting the HOMA-IR in the line dance group. Therefore, regular and continuous line dance exercise will be effective for preventing the life-style diseases with improvement of the energy metabolic factors and insulin resistance by decreasing the body fat.】

The purpose of this study was to find out the effects of music rope-skipping on health fitness, blood lipids and growth-related factors in male middle school students. For this purpose, twenty subjects were participated in this study and the participants were 'After School Class' boys in B middle school located in Gimhae City. They divided into exercise group(n=10) and control group(n=10). Exercise group conducted 45minutes per a day, four times a week for 12 weeks. And the control group continued their normal life. The results were as follows; First, in exercise group, lean body mass, muscular strength, muscular endurance, cardiovascular endurance and flexibility were all significantly increased after program execution. But %body fat was significantly decreased. In control group, muscular strength, muscular endurance and cardiovascular endurance were significantly increased. There were significant differences in lean body mass, %body fat, muscular strength and flexibility between two groups after program execution. Second, in exercise group, HDL-C was significantly increased after program execution. In control group, TG was significantly decreased. But HDL-C was significantly increased. There were no significant differences in all blood lipids(TC, TG, HDL-C and LDL-C) between two groups after program execution. Third, in exercise group, GH and IGF-Ⅰ were significantly increased after program execution. In control group, IGF-Ⅰ was significantly decreased. There were significant differences in IGF-I between two groups after program execution. These results indicate that music rope-skipping is effective to improve lean body mass, muscular strength, flexibility, GH and IGF-I in normal middle school male students.

Background/Aims This study was performed to investigate the correlation of sodium iodide symporter (NIS) expression with the functionality and loss of phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression in human cholangiocarcinoma (CCA). Methods Immunohistochemistry for the expression of NIS and PTEN was performed in 60 biopsy specimens of CCA. The clinicopathological parameters were retrospectively identified from medical records. The expression pattern of NIS and loss of PTEN expression were analyzed in association with the clinicopathological characteristics, including survival. Results Normal biliary trees displayed NIS expression, but hepatocytes did not. NIS expression was divided into two patterns: cytoplasmic and membranous. Fifty-nine cases, all except for one case, displayed NIS expression in tumor cells. Twenty-two cases (33.3%) were mixed pattern, and 39 cases (65.05%) were cytoplasmic pattern; the pure membranous pattern was not noted. There was no association between the NIS expression pattern and clinicopathological parameters, including age, sex, differentiation grade, T stage and tumor, node, metastasis stage (p>0.05). The survival rates were similar among various NIS expression patterns. Normal hepatocytes and biliary trees exhibited PTEN expression in the nucleus and cytoplasm. CCA cells displayed nuclear staining. Thirty-six (60.0%) of 60 cases displayed a loss of PTEN expression. The loss of PTEN expression was observed in the advanced T-stage group (p=0.0036), but there was no association between the loss of PTEN expression and other clinicopathological parameters (p>0.05). No association between the loss of PTEN expression and survival was noted. Conclusions NIS is expressed in most types of human CCA. The expression pattern suggests a role in cancer development. PTEN loss expression is common in the context of human CCA, especially in the advanced T stage.

OBJECTIVE To determine the association of regular exercise, BMI, and fasting glucose with the risk of type 2 diabetes and to predict the risk. RESEARCH DESIGN AND METHODS Korean subjects (n = 7,233; 40–79 years old) who were not diagnosed with diabetes at baseline were enrolled through the National Health Insurance Corporation. All participants underwent biennial examinations, and 1,947 of 7,233 subjects also underwent a 6-month program of moderate-intensity exercise (300 min/week) without dietary advice. RESULTS During follow-up (mean = 2 years), there were 303 incidents of type 2 diabetes in the nonexercise program group (n = 5,286) and 83 in the exercise program group (n = 1,947). After adjusting for confounders, the risk of type 2 diabetes was positively associated with BMI and inversely with regular exercise, especially among overweight/obese subjects. After further adjustment for BMI, the odds ratios for risk of diabetes associated without and with regular exercise were 1.00 and 0.77, respectively. Among subjects with normal fasting glucose, exercise reduced the diabetes risk; however, among those with impaired fasting glucose (IFG), the protective effect of exercise was found only among overweight/obese subjects. The overweight/obese subjects in the exercise program group exhibited improved fasting glucose compared with the nonexercise program group and showed 1.5 kg of weight loss and a 3-cm decrease in waist circumference. Among overweight/obese subjects with unchanged fasting glucose, weight loss was greater in the exercise program group. CONCLUSIONS Regular exercise reduces the risk of type 2 diabetes in overweight/obese individuals. Particularly, regular exercise and weight or waist circumference control are critical factors for preventing diabetes in overweight/obese individuals with IFG.

Objective To determine whether circulating metabolic intermediates are associated with inflammation, oxidative stress and arterial stiffness in men with newly diagnosed type 2 diabetes and investigate the circulating metabolic intermediates that may predict the risk of developing diabetes. Research design and methods Men with newly diagnosed type 2 diabetes (n = 26) and age- and body mass index-matched nondiabetic men (n = 27) were included. We measured inflammatory and oxidative markers and arterial stiffness by brachial-ankle pulse wave velocity (ba-PWV). Metabolomic profiling was analysed with ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry. Results Diabetic men showed higher circulating levels of glucose, triglyceride, oxidized low-density lipoprotein (LDL), high-sensitivity C-reactive protein, interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α), homeostasis model assessment-insulin resistance, urinary 8-epi-prostaglandin F(2α) (8-epi-PGF(2α)) and ba-PWV than nondiabetic men. In plasma, 19 metabolites including three amino acids, eight acylcarnitines, six lysophosphatidylcholines (lysoPCs), and two lysophosphatidylethanolamines (lysoPEs; C18:2 and C22:6) significantly increased in diabetes men, whereas serine and lysoPE (C18:1) decreased. Decanoyl carnitine, lysoPCs (C14:0, C16:1, C18:1 and C22:6) and lysoPE (C18:1) with variable importance in the projection values >1·0 were major plasma metabolites that distinguished nondiabetic and diabetic men. Decanoyl carnitine positively correlated with oxidized LDL, 8-epi-PGF(2α), IL-6, TNF-α and ba-PWV. ba-PWV correlated positively with lysoPCs C14:0 and C16:1, and negatively with lysoPE C18:1. 8-epi-PGF(2α) correlated positively with lipoprotein-associated phospholipase A(2), ba-PWV and lysoPCs (C14:0 and C16:1). The receiver operating characteristic curve estimation suggested that decanoyl carnitine and lysoPC (C14:0) are the best metabolites for predicting the risk of developing diabetes. Conclusions Circulating lipid-related intermediate metabolites can be closely associated with inflammation, oxidative stress and arterial stiffness in early diabetes.

The rapid pace of neuroscience research demands equally efficient and flexible methods for genetically manipulating and visualizing selected neurons within the rodent brain. The use of viral vectors for gene delivery saves the time and cost of traditional germline transgenesis and offers the versatility of readily available reagents that can be easily customized to meet individual experimental needs. Here, we present a protocol for widespread neuronal transduction based on intraventricular viral injection of the neonatal mouse brain. Injections can be done either free-hand or assisted by a stereotaxic device to produce lifelong expression of virally delivered transgenes.

This study examined the relationships between plasma levels of adiponectin and the features of the atherogenic lipoprotein phenotype (ALP), including HDL subclasses.Blood lipids and apolipoproteins were measured in 293 healthy individuals. LDL particle size and HDL subspecies (HDL(2), HDL(3)) were measured using gradient gel electrophoresis. Plasma adiponectin levels were negatively correlated with levels of apoB (r=-0.199, p0.001), TG (r=-0.262, p0.001), and HOMA-IR (r=-0.323, p0.001) and positively correlated with levels of apoAI (r=0.173, p=0.006), HDL-cholesterol (r=0.287, p0.001), and LDL particle size (r=0.289, p0.001). Multiple linear regression analysis revealed the relationship between plasma adiponectin and LDL particle size (p0.05) was no longer significant after adjusting for plasma TG levels. However, adiponectin (p0.005) together with apoAI and TG were independent factors for HDL-cholesterol. With regard to HDL subclasses, plasma adiponectin levels were positively correlated with HDL(2b) (r=0.204, p0.001), HDL(2a) (r=0.132, p0.05) and negatively with HDL(3a) (r=-0.128, p0.05), HDL(3b) (r=-0.203, p0.001), and HDL(3c) (r=-0.159, p0.01). The relationship between circulating adiponectin and HDL(2) (HDL(2b)+HDL(2a)) was independent of apoB and TG levels (p0.05), but not of apoAI and HOMA-IR.Our results show that circulating adiponectin is associated with reduced manifestations of ALP.

본 연구는 남녀 대학생들의 비만과 대사증후군 유병률을 알아보고, BMI와 대사증후군 위험인자의 관계를 비교 분석함으로써 대학생의 만성 질환 이환율을 낮추고 well-being에 대한 인식을 높이고자 한다. B광역시 P대학 건강관련 교양과목 수강생인 남녀 대학생 848명을 대상으로 BMI기준에 따라 UWG, NWG, OWG, OG로 나누어 남녀 각각 대사증후군 위험인자를 측정하였다. 총 대상자에서 비만(BMI ${\geq}$ 25 kg/ $m^2$ ) 유병률은 12. 61%, 과체중(BMI 23-24.9 kg/ $m^2$ )은 31.36%로 나타났다. 대사증후군의 위험인자가 3개 이상의 기준을 만족한 학생은 0.35%(3명), 2개만 가지고 있는 학생은 3.41%(29명)로 낮게 나타났다. 그러나 대사증후군 위험인자를 적어도 1개 가지고 있는 대상자는 29.71%(252명)로 높은 수준을 보였다. BMI와 대사증후군 위험인자에 대한 그룹간 비교를 보면, 남자 대학생의 경우 BMI가 높은 그룹이 낮은 그룹보다 glucose를 제외한 허리둘레, TG, BP에서 더 높게 나타났으며, HDL-C에서는 더 낮게 나타났다. 여자 대학생의 경우 허리둘레와 BP에서 BMI가 높은 그룹이 더 높게 나타났으며, TG, HDL, glucose에서는 그룹간 차이가 없었다. 【The purpose of this study was to evaluate the prevalence of the obesity and metabolic syndrome of the university students and to contribute to the development of the national health promotion through the comparative analysis on the risk factors of the metabolic syndrome by BMI level. The subjects for the study were 848(445 men and 403 women) college students. That is underweight group(18.5 kg/ $m^2$ ${\leq}$ BMI, UWG) 28(6%) men, 86(21%) women, normal weight group(18.5 kg/ $m^2$ $m^2$ , NWG) 218(49%) men, 250(62%) women, overweight group(23 kg/ $m^2$ ${\leq}$ BMI $m^2$ , OWG) 117(26%) men, 42(11%) women, obesity group(25 kg/ $m^2$ ${\leq}$ BMI, OG) 82(19%)man, 25(6%) women based on BMI standard of classification by WHO(2004). The conclusions were as follow. This result are necessary to evaluate the fitness of the university students. Because we can recognize and prevent the negative factor that could be produced during young adults we know the risk factors that could be chronic disease.】

We examined the effects of quercetin-rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet-induced obese animal model. Male Sprague-Dawley rats (n = 24) were randomly assigned into control (n = 8), high fat diet (HF, n = 8) and high fat diet with onion peel extract (HFOE, n = 8). After 8 weeks, serum biochemical parameters, weights of adipose tissues (epididymal, perirenal and mesenteric fats) and adipokine mRNA levels (adiponectin, IL (interleukin)-6 and visfatin) along with PPAR (peroxisome proliferator-activated receptor) γ2 from adipose tissues were measured. After the 8 week supplementation, mesenteric fat weights were lower in the HFOE group than the HF group (p

This study aimed to examine the association of dietary vitamin intakes with plasma pro-inflammatory cytokine levels in Korean heart failure patients. Stable outpatients with heart failure were recruited and finally 91 patients were included. Dietary intakes were estimated by a developed semi-quantitative food frequency questionnaire. The simultaneous measurement of 17 cytokines was performed along with analysis of plasma C-reactive protein. Plasma C-reactive protein levels significantly correlated with dietary intakes of vitamin C (r = −0.30, p

Inappropriate interleukin-6 production is thought to play a role in the development of several age-related conditions including atherosclerosis. This study aimed to determine whether aging affects circulating interleukin-6 (IL-6) levels. Healthy, nonobese women (n = 208, 44.5 ± 0.70 years, 22.4 ± 0.17 kg/m2) were categorized into four age groups (22–31, 32–41, 42–51, and 52–63 years; cross-sectional study). Cytokine levels in serum and those produced from peripheral blood mononuclear cell (PBMC) were measured. The oldest group had the highest circulating levels of IL-6 and oxidized low-density lipoprotein (ox-LDL) and higher PBMC production of IL-6, tumor necrosis factor-α (TNF-α), and interleukin-1 alpha (IL-1β). Additionally, significant interactions between age and menopause were found for serum IL-6 (P = 0.024), and TNF-α (P = 0.011) and IL-1β (P

Objectives This study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques. Design and methods Comparison of protein expression in plasma between non-obese (n = 109, body mass index, BMI

Objective: The objective was to determine the effects of lycopene supplementation on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and oxidative stress. Methods: Healthy men (n = 126) were randomized to receive placebo (n = 38), 6 mg (n = 41), or 15 mg (n = 37) lycopene daily for 8-week. Results: Serum lycopene increased in a dose-dependent manner after 8-week supplementation (P < 0.001). The 15 mg/day group had greater increase in plasma SOD activity (P = 0.014) and reduction in lymphocyte DNA comet tail length (P = 0.042) than the placebo group. Intragroup comparison revealed a 23% increase in RH-PAT index from baseline (1.45 ± 0.09 vs. 1.79 ± 0.12; P = 0.032) in the 15 mg/day group after 8week. hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 significantly decreased, and -carotene and LDL-particle size significantly increased only in the 15 mg/day group. Interestingly, the beneficial effect of lycopene supplementation on endothelial function (i.e., RH-PAT and sVCAM-1) were remarkable in subjects with relatively impaired endothelial cell function at initial level. Changes in RH-PAT index correlated with SOD activity (r = 0.234, P = 0.017) especially in the 15 mg lycopene/day group (r = 0.485, P = 0.003), lymphocyte DNA comet tail moment (r = −0.318, P = 0.001), and hs-CRP (r = −0.238, P = 0.011). In addition, changes in lycopene correlated with hs-CRP (r = −0.230, P = 0.016) and SOD activity (r = 0.205, P = 0.037). Conclusion: An increase in serum lycopene after supplementation can reduce oxidative stress which may play a role in endothelial function.

Objective We investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans. Methods In this case–control study, CAD patients ( n =756, 40–79 years) and healthy controls ( n =890) were genotyped for rs174537 near FADS1 ( FEN1 rs174537G>T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide. Results Among four SNPs, only rs174537G>T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia ( P =0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61–0.92), P =0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F 2α in both control and CAD groups. Conclusion The rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.

We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:4ω6) and the APOA5-1131T>C on phospholipid ω6PUFA and coronary artery disease (CAD). Patients with CAD (n = 807, 27–81 years of age) and healthy controls (n = 1123) were genotyped for FEN1 10154G>T and APOA5-1131T>C. We found a significant interaction between these two genes for CAD risk (P = 0.007) adjusted for confounding factors. APOA5-1131C allele carriers had a higher CAD risk [odds ratio (OR):1.484, 95% confidence interval (CI):1.31–1.96; P = 0.005] compared with APOA5-1131TT individuals in the FEN1 10154GG genotype group but not in the FEN1 10154T allele group (OR:1.096, 95%CI:0.84–1.43; P = 0.504). Significant interactions between these two genes were also observed for the AA proportion (P = 0.04) and the ratio of AA/linoleic acid (LA, 18:2ω6) (P = 0.004) in serum phospholipids of controls. The APOA5-1131C allele was associated with lower AA (P = 0.027) and AA/LA (P = 0.014) only in controls carrying the FEN1 10154T allele. In conclusion, the interaction between these genes suggests that the FEN1 10154T variant allele decreases AA and AA/LA in the serum phospholipids of carriers of the APOA5-1131C allele, but contributes no significant increase in CAD risk for this population subset despite their increased triglylcerides and decreased apoA5.

Fatty acids (FAs) are essential nutrients and main constituents of cell membranes that are involved in the signaling pathway and associated with health conditions. We investigated if blood or erythrocyte membrane FAs can predict the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and related complications. Omega-3 (n-3) FAs are important predictors for metabolic syndrome, diabetes, CVD, and CKD risks, and the n-3 index is also a good biomarker for sudden cardiac death in coronary artery disease. Linoleic acid, which is one of the major n-6 FAs reflecting recent dietary FA intake, may predict CVD risk and mortality in the general population and patients with CKD. Monounsaturated FAs (MUFAs) are also related to diabetes or diabetic nephropathy. Oleic acid, a major MUFA, is an emerging marker that is related to acute coronary syndrome, low glomerular filtration rate, and vascular calcification in patients with CKD, and can be modified by n-3 FA supplementation. Saturated FAs, trans-FAs, and FA desaturation/elongation are associated with CVD risk; however, few studies have been conducted on patients with CKD. In summary, blood or erythrocyte membrane FA measurements are important for CVD and CKD risk prediction and management. Further studies are needed to elucidate the FAs for their risk predictions.

Previous studies report that organo-sulfur compounds derived from garlic inhibited smooth muscle cell (SMC) proliferation and induced apoptosis of cancer cells. Recently, lipid-soluble compounds such as diallyl sulfides (DAS) and diallyl disulfides (DADS) have been reported to more effectively suppress tumor cell proliferation. However, there were few studies on the suppressive effects of lipid-soluble garlic sulfur compounds on the proliferation and migration of vascular smooth muscle cells (VSMC). Therefore, this study investigated the effect of DAS and DADS on VSMC proliferation/migration induced by oleic acid (OA), a principal fatty acid in circulating triglyceride of blood stream. Assays performed include a tetrazole (MTT) assay, a wound healing assay and a Western blots. VSMC proliferations were enhanced by OA in a dose-dependent manner at concentrations of 10～50 µM and inhibited by DAS and DADS compared to non-treated control. OA-induced proliferations were also attenuated by DAS and DADS. OA-induced cell migrations were 2.5 times higher than non-treated control, and they were significantly attenuated by DAS (32% at 150 µM and 50% at 200 µM) and DADS (40% at 150 µM and 46% at 200 µM). OA-induced cell migration was also attenuated by PD98059 (ERK inhibitor), SB203580 (P38 inhibitor) and particularly by LY204002 (PI3K inhibitor) and SP600125 (JNK2 inhibitor). Additionally, Western blot assays showed that OA-induced JNK1/2-phosphorylation was down-regulated after treatment with DAS and DADS. In conclusion, the findings of our study support the idea that DAS and DADS may have a suppressive effect on the proliferation and migration of OA-induced VSMC and that this effect may be partly associated with PI3K and JNK2 pathways.