LPC20K modified from krill oil ameliorates the scopolamine-induced cognitive impairment.

Alzheimer's disease (AD) is characterized by cognitive impairment. It is common in the elderly. Etiologically, dysfunction of cholinergic neurotransmitter system is prominent in AD. However, disease modifying drug for AD is still unavailable. We hypothesized that krill oil and modified krill oil containing 20 % lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA, LPC20K) could play a crucial role in AD by improving cognitive functions measured by several behavioral tests. We found that LPC20K could ameliorate short-term, long-term, spatial, and object recognition memory under cholinergic hypofunction states. To find the underlying mechanism involved in the effect of LPC20K on cognitive function, we investigated changes of signaling molecules using Western blotting. Expression levels of protein kinase C zeta (PKCζ) and postsynaptic density protein 95 (PSD-95), and phosphorylation levels of extracellular signal-regulated kinase (ERK), Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), and cAMP response element-binding protein (CREB) were significantly increased in LPC20K-administered group compared to those in the memory impairment group. Moreover, the expression levels of BDNF were temporally increased especially 6 or 9 h after administration of LPC20K compared with the control group. These results suggest that LPC20K could ameliorate memory impairment caused by hypocholinergic state by enhancing the expression levels of PKCζ and PSD-95, and phosphorylation levels of ERK, CaMKⅡ and CREB and increasing BDNF expression levels. Therefore, LPC20K could be used as a dietary supplement against cognitive impairment observed in diseases such as AD with a hypocholinergic state.

The moderating role of circadian gene polymorphisms in the relationship between sleep disturbance and circulating lymphocyte subsets in colorectal cancer patients.

AIM: We investigated the impact of sleep disturbance on immune status in colorectal cancer (CRC) patients with consideration of the moderating role of circadian clock gene polymorphisms. METHODS: A prospective longitudinal study design was used to collect information regarding sleep disturbance. Blood samples for immunologic assays were obtained the day before the first (baseline) and last cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical sleep disturbance was compared between the two-time points using the Pittsburgh Sleep Quality Index (PSQI) global score. We analysed single-nucleotide polymorphisms in rs2278749, rs3749474, rs2291738, rs17031614, and rs2287161. The dependent variables included changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two-time points. The results were analysed using moderated regression analysis; the p-values were adjusted using the false discovery rate. RESULTS: Among the 104 patients, no significant dyadic associations were observed between changes in lymphocyte percentages and the PSQI global score. However, the moderated regression analysis revealed five significant associations (rs2287161 with CD8+, rs2278749 and rs2291738 with CD19+, and rs17031614 with CD4+ and CD16/56+ lymphocytes). The inclusion of each interaction resulted in a significant increase (5.7-10.7%) in the variance explained by changes in lymphocyte percentage. CONCLUSION: Patients with specific circadian gene allele types may be more susceptible to immune dysregulation when experiencing sleep disturbances. Considering that sleep disturbance is a modifiable factor that can impact immune regulation, it is essential to prioritise the management of sleep disturbances in CRC patients receiving FOLFOX chemotherapy.

Enhanced γ-aminobutyric acid and sialic acid in fermented deer antler velvet and immune promoting effects.

Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei, L. rhamnosus, L. brevis, and L. plantarum, and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 (L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans. Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24 h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi, and Listeria monocytogenes. To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo. We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007.

The Association between Plasma Concentration of Phytoestrogens and Hypertension within the Korean Multicenter Cancer Cohort.

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case-control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20-0.57; enterolactone, OR = 0.32, 95%CI 0.18-0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26-0.96; OR = 0.38, 95%CI 0.19-0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22-0.81; OR = 0.28, 95%CI 0.14-0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p-heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

Bacillus amyloliquefaciens SCGB1 Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice Through Immune Regulation.

Probiotics, as living microorganisms, exert health benefits to the host by alleviating excess inflammation through modulating the immune system and establishing intestinal homeostasis. In this study, we evaluated the probiotic characteristics and inflammation alleviatory effects of Bacillus amyloliquefaciens isolated from traditional Korean fermented foods. The strains withstood the acidic environment of the digestive process, extended the lifespan of Caenorhabditis elegans, and enhanced pmk-1 expression. However, only B. amyloliquefaciens SCGB1 could attach to C. elegans in the intestines, which enhanced their survival upon exposure to Escherichia coli O157:H7. We also investigated the anti-inflammatory effect of SCGB1 using the RAW264.7 macrophage stimulated with lipopolysaccharide. The strain treatment enhanced anti-inflammatory cytokine interleukin (IL)-10 secretion and downregulated proinflammatory cytokine IL-6 expression in vitro. Next, we used a dextran sulfate sodium (DSS)-induced colitis mouse model to investigate whether SCGB1 can ameliorate gut inflammation in vivo. Compared to those in the DSS-induced mice, histological damage and IL-6 cytokine levels were significantly reduced in SCGB1-fed mice. These results suggest that B. amyloliquefaciens SCGB1 as potential probiotics may have health-promoting effects by reduction of inflammatory responses.

Travel time to emergency care not by geographic time, but by optimal time: A nationwide cross-sectional study for establishing optimal hospital access time to emergency medical care in South Korea.

Increase in travel time, beyond a critical point, to emergency care may lead to a residential disparity in the outcome of patients with acute conditions. However, few studies have evaluated the evidence of travel time benchmarks in view of the association between travel time and outcome. Thus, this study aimed to establish the optimal hospital access time (OHAT) for emergency care in South Korea. We used nationwide healthcare claims data collected by the National Health Insurance System database of South Korea. Claims data of 445,548 patients who had visited emergency centers between January 1, 2006 and December 31, 2014 were analyzed. Travel time, by vehicle from the residence of the patient, to the emergency center was calculated. Thirteen emergency care-sensitive conditions (ECSCs) were selected by a multidisciplinary expert panel. The 30-day mortality after discharge was set as the outcome measure of emergency care. A change-point analysis was performed to identify the threshold where the mortality of ECSCs changed significantly. The differences in risk-adjusted mortality between patients living outside of OHAT and those living inside OHAT were evaluated. Five ECSCs showed a significant threshold where the mortality changed according to their OHAT. These were intracranial injury, acute myocardial infarction, other acute ischemic heart disease, fracture of the femur, and sepsis. The calculated OHAT were 71-80 min, 31-40 min, 70-80 min, 41-50 min, and 61-70 min, respectively. Those who lived outside the OHAT had higher risks of death, even after adjustment (adjusted OR: 1.04-7.21; 95% CI: 1.03-26.34). In conclusion, the OHAT for emergency care with no significant increase in mortality is in the 31-80 min range. Optimal travel time to hospital should be established by optimal time for outcomes, and not by geographic time, to resolve the disparities in geographical accessibility to emergency care.

Waste nutrient solutions from full-scale open hydroponic cultivation: Dynamics of effluent quality and removal of nitrogen and phosphorus using a pilot-scale sequencing batch reactor.

Hydroponic cultivation is revolutionizing agricultural crop production techniques all over the world owing to its minimal environmental footprint, enhanced pest control, and high crop yield. However, waste nutrient solutions (WNS) generated from hydroponic systems contain high concentrations of N and P; moreover, they are discharged into surface and subsurface environments, leading to eutrophication and subsequent ecosystem degradation. In this study, the nutrient concentrations in WNS from 10 hydroponic indoor tomato, capsicum, and strawberry farms (greenhouses) were monitored for up to six months. The concentrations of N and P in WNS discharged from these farms were 48.0-494.0 mg L-1 and 12.7-96.9 mg L-1, respectively, which exceeded the Korean water quality guidelines (40.0 mg L-1 N and 4.0 mg L-1 P) for effluents. These concentrations were varied and dependent on the supplied nutrient concentrations, crop types, and growth stages. In general, the concentrations of N and P were in the following order: tomato > capsicum > strawberry. High N as NO3- and P as PO43- but low organic C in WNS warrant subsequent treatment before discharge. Therefore, this study tested a pilot-scale sequencing batch reactor (SBR) system as a potential technology for WNS treatment. The SBR system had BOD, COD, nitrate, and phosphate removal efficiency of 100, 100, 89.5, and 99.8%, respectively. In addition, the SBR system removed other cations such as Ca2+, dissolved Fe, K+, Mg2+, and Na+ and the removal efficiencies of those ions were 48, 67, 18, 14 and 15%, respectively. Lower methanol addition (0.63 mg L-1) and extended aeration (~30 min) improved SBR performance efficiency of C, N, and P removal. Thus, SBR showed significant promise as a treatment alternative to WNS pollutants originating from hydroponic systems.

Low dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean patients with schizophrenia and the development of dietary guidelines for schizophrenia.

Inappropriate dietary intake and poor nutritional status are reported to be associated with metabolic syndrome and psychopathology in patients with schizophrenia. We hypothesized that inappropriate dietary habits and insufficient dietary intake of specific nutrients are associated with schizophrenia. To test the hypothesis, we assessed the dietary habits and nutritional intake of patients with schizophrenia and then developed suitable dietary guidelines. In total, 140 subjects (73 controls and 67 patients with schizophrenia from community mental health centers) were included, and dietary intakes were analyzed using a semi-quantitative food frequency questionnaire. As a result, the proportion of overweight or obese patients was significantly higher in schizophrenia subjects (64.2%) compared with control subjects (39.7%) (P=.004). The male schizophrenia patients had significantly lower dietary intakes of protein, polyunsaturated fatty acids (PUFAs), vitamin K, niacin, folate, and vitamin C than the male control subjects. In all multiple logistic regression models, subjects with the "low" dietary intake of protein, n-3 PUFAs, niacin, folate, and vitamin C had a significantly higher odds ratios for schizophrenia compared with those with the "high" dietary intake category of each nutrient. Therefore, maintenance of a healthy body weight and sufficient dietary intake of protein, PUFAs, niacin, folate, and vitamin C are recommended for Korean patients with schizophrenia.

Using the National Health Information Database of the National Health Insurance Service in Korea for Monitoring Mortality and Life Expectancy at National and Local Levels.

This study explores whether the National Health Information Database (NHID) can be used to monitor health status of entire population in Korea. We calculated the crude mortality rate and life expectancy (LE) at birth across the national, provincial, and municipal levels using the NHID eligibility database from 2004 to 2015, and compared the results with the corresponding values obtained from the Korean Statistical Information Service (KOSIS) of Statistics Korea. The study results showed that the ratio of crude mortality rate between the two data was 0.99. The absolute difference between the LE of the two data was not more than 0.5 years, and did not exceed 0.3 years in gender specific results. The concordance correlation coefficients (CCC) between the crude mortality rates from NHID and the rates from KOSIS ranged 0.997-0.999 among the municipalities. For LE, the CCC between the NHID and KOSIS across the municipalities were 0.990 in 2004-2009 and 0.985 in 2010-2015 among men, and 0.952 in 2004-2009 and 0.914 in 2010-2015 among women, respectively. Overall, the NHID was a good source for monitoring mortality and LE across national, provincial, and municipal levels with the population representativeness of entire Korean population. The results of this study indicate that NHID may well contribute to the national health promotion policy as a part of the health and health equity monitoring system.

Study on the Depth, Rate, Shape, and Strength of Pulse with Cardiovascular Simulator.

Pulse diagnosis is important in oriental medicine. The purpose of this study is explaining the mechanisms of pulse with a cardiovascular simulator. The simulator is comprised of the pulse generating part, the vessel part, and the measurement part. The pulse generating part was composed of motor, slider-crank mechanism, and piston pump. The vessel part, which was composed with the aorta and a radial artery, was fabricated with silicon to implement pulse wave propagation. The pulse parameters, such as the depth, rate, shape, and strength, were simulated. With changing the mean pressure, the floating pulse and the sunken pulse were generated. The change of heart rate generated the slow pulse and the rapid pulse. The control of the superposition time of the reflected wave generated the string-like pulse and the slippery pulse. With changing the pulse pressure, the vacuous pulse and the replete pulse were generated. The generated pulses showed good agreements with the typical pulses.

A formulated red ginseng extract upregulates CHOP and increases TRAIL-mediated cytotoxicity in human hepatocellular carcinoma cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because its cytotoxicity is selective for tumor cells. Despite promising outcomes in clinical trials using this ligand, sustained clinical responses have been impeded because cancer cells acquire resistance to TRAIL-based therapies. Ginseng, a well-known food product consumed globally, has been reported to reduce fatigue and possess antioxidant and antitumor activities. We explored the sensitizing influence of a formulated red ginseng extract (RGE) on TRAIL-derived cell death in hepatocellular carcinoma (HCC) cell lines and the underlying molecular mechanisms responsible for TRAIL sensitization. We found that the RGE promoted TRAIL-derived apoptosis in HepG2, Huh-7 and Hep3B cell lines. We also found that death receptor 5 expression was induced by the RGE and mediated by C/EBP homologous protein (CHOP). shRNA-induced downregulation of CHOP expression effectively suppressed cell death induced by combined treatment with the RGE and TRAIL in the HepG2 cell line, indicating that RGE-related upregulation of the CHOP protein plays an important role in sensitizing TRAIL-derived apoptosis. In summary, we showed that the RGE sensitized human HCC cell lines to TRAIL-derived cell death and could be utilized as a dietary supplement in combination with cancer treatment.

SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii.

Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1-4) and 5 were evaluated for SARS-CoV 3CL(pro) inhibitory activities and showed potent inhibitory activities with IC(50) values of 10.3, 5.5, 9.9, and 2.6 microM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC(50)=21.7 microM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1-4 have proven to be competitive by the kinetic analysis.

The radioprotective effects of the hexane and ethyl acetate extracts of Callophyllis japonica in mice that undergo whole body irradiation.

The radioprotective activity of extracts from the red seaweed Callophyllis (C.) japonica was investigated in mice that underwent whole-body exposure to gamma radiation. A methanol extract of C. japonica and its fractions [hexane, ethyl acetate (EtOAc), butanol and the remaining H2O] were used. Each fraction (100 mg/kg body weight) was administered intraperitoneally (i.p.) 2 times into the BALB/c mice, once at 1 and once at 24 h before exposure to 9 Gray (Gy) of gamma radiation. Pre-irradiation administration of the hexane and EtOAc fractions saved the mice, with their survival rates being greater than 80% at 30 days post-irradiation; the mice that were pretreated with the other fractions showed survival rates lower than 20% over the same time period. To examine the effect of each C. japonica fraction on the survival of intestinal and bone marrow stem cells, the number of intestinal crypts and bone marrow cells in the gamma-irradiated mice were examined. Pre-treatment of mice (i.p., 100 mg/kg body weight at 1 and 24 h before irradiation) with the hexane or EtOAc fraction prior to 6-Gy irradiation significantly protected the number of jejunal crypts and bone marrow cells at 9 days after irradiation. These findings suggest that certain extracts from C. japonica, when they are administered prior to irradiation, play an important role in the survival of irradiated mice, and this is possibly due to the extracts protecting the hematopoietic cells and intestinal stem cells against gamma irradiation.

Saengshik, a formulated health food, prevents liver damage in CCl4-induced mice and increases antioxidant activity in elderly women.

Saengshik is a Korean noncooked food made with of more than 30 different whole gains, vegetables, fruits, mushrooms, and seaweeds. All of these ingredients are frozen and dried to minimize the loss of nutrients. Saengshik has become popular among health-conscious people in the Republic of Korea. The study aims to investigate antioxidant effects of Saengshik by in vivo and human experiments. In in vivo tests, mice were fed Saengshik for 4 weeks, and oxidative damage was induced by CCl(4). Then the effects of Saengshik on oxidative damage were examined. It was found that plasma lipid hydroperoxide and protein oxidative damages were significantly suppressed and antioxidants, glutathione, and thiol groups were increased. The activity of the antioxidant enzyme superoxide dismutase was increased, and the level of glutamate pyruvate transaminase was decreased. In a human study, elderly people were given Saengshik for 24 weeks, and changes in antioxidant defense of the body were examined. Antioxidant activities in plasma were enhanced, although the difference was not significant. Therefore, it is expected that Saengshik is effective at removing oxidants from body tissues, preventing oxidative damage, and eventually boosting the antioxidant capacity of the body.

Selection of high ginsenoside producing ginseng hairy root lines using targeted metabolic analysis.

To develop an experimental system for studying ginsenoside biosynthesis, we generated thousands of ginseng (Panax ginseng C.A. Meyer) hairy roots, genetically transformed roots induced by Agrobacterium rhizogenes, and analyzed the ginsenosides in the samples. 27 putative ginsenosides were detected in ginseng hairy roots. Quantitative and qualitative variations in the seven major ginsenosides were profiled in 993 ginseng hairy root lines using LC/MS and HPLC-UV. Cluster analysis of metabolic profiling data enabled us to select hairy root lines, which varied significantly in ginsenoside production. We selected hairy root lines producing total ginsenoside contents 4-5 times higher than that of a common hairy root population, as well as lines that varied in the ratio of the protopanaxadiol to protopanaxatriol type ginsenoside. Some of the hairy root lines produce only a single ginsenoside in relatively high amounts. These metabolites represent the end product of gene expression, thus metabolic profiling can give a broad view of the biochemical status or biochemical phenotype of a hairy root line that can be directly linked to gene function.