Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA-RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations featured in sequencing, we discovered widespread position-specific o8Gs in tumour microRNAs, preferentially oxidized towards 5' end seed regions (positions 2-8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma. We validated that o8G at position 4 of miR-124 (4o8G-miR-124) and 4o8G-let-7 suppress lower-grade gliomas, whereas 3o8G-miR-122 and 4o8G-let-7 promote malignancy of liver hepatocellular carcinoma by redirecting the target transcriptome to oncogenic regulatory pathways. Stepwise oxidation from tumour-promoting 3o8G-miR-122 to tumour-suppressing 2,3o8G-miR-122 occurs and its specific modulation in mouse liver effectively attenuates diethylnitrosamine-induced hepatocarcinogenesis. These findings provide resources and insights into epitranscriptional o8G regulation of microRNA functions, reprogrammed by redox changes, implicating its control for cancer treatment.

Chemical stability of active ingredients in diluted veterinary disinfectant solutions under simulated storage conditions.

Introduction: The product labels of veterinary disinfectants specify their expiration dates to prevent the use of outdated products, as these may result in disinfection and biosecurity failures during outbreak situations. However, a clear standard for the storage conditions of diluted disinfectant solutions has not yet been established, and the effects of storage conditions have scarcely been investigated. To fill this research gap, our study examined the stability of the active ingredients of diluted veterinary disinfectants based on their change in concentrations when stored at various temperatures for various time periods. Methods: Twenty veterinary disinfectants effective against either foot-and-mouth disease or avian influenza viruses were selected. The disinfectants were diluted to effective concentrations following the manufacturer's instructions. Using selective analytical techniques, the concentrations of the active ingredients of the samples that had been stored for varying intervals at different temperatures (4, 20, 30, and 45°C) were determined. These samples included soaps and detergents, acids, oxidizing agents, aldehydes, and copper compounds. The active ingredient concentrations of two of the samples were determined following freezing/thawing cycle, to establish their stability when exposed to simulated winter conditions. Results: Our results showed that most of the active ingredients had concentrations of 90% or greater of their initial concentrations, indicating ≥90% stability over a 21-day period under the experimental storage conditions. However, there were some exceptions. Glutaraldehyde, formaldehyde, and malic acid are over 90% stable at ≤ 30°C for 21 days, but their concentrations decreased to below 90% of their initial concentrations at 45°C, indicating a decline in stability when stored at 45°C for 21 days. The concentrations of potassium peroxymonosulfate and peracetic acid rapidly declined with increasing time and temperature to less than 90% of their initial concentrations. Discussion: Based on our findings, we propose that diluted disinfectant solutions should preferably be prepared daily. However, if the daily preparation of a diluted disinfectant solution is not feasible, then our results can be used as a reference, providing basic scientific data on the chemical stability of diluted disinfectant solutions commonly used in the veterinary field, thus indicating suitable storage conditions.

AGO CLIP-based imputation of potent siRNA sequences targeting SARS-CoV-2 with antifibrotic miRNA-like activity.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with fatal pulmonary fibrosis. Small interfering RNAs (siRNAs) can be developed to induce RNA interference against SARS-CoV-2, and their susceptible target sites can be inferred by Argonaute crosslinking immunoprecipitation sequencing (AGO CLIP). Here, by reanalysing AGO CLIP data in RNA viruses, we delineated putative AGO binding in the conserved non-structural protein 12 (nsp12) region encoding RNA-dependent RNA polymerase (RdRP) in SARS-CoV-2. We utilised the inferred AGO binding to optimise the local RNA folding parameter to calculate target accessibility and predict all potent siRNA target sites in the SARS-CoV-2 genome, avoiding sequence variants. siRNAs loaded onto AGO also repressed seed (positions 2-8)-matched transcripts by acting as microRNAs (miRNAs). To utilise this, we further screened 13 potential siRNAs whose seed sequences were matched to known antifibrotic miRNAs and confirmed their miRNA-like activity. A miR-27-mimicking siRNA designed to target the nsp12 region (27/RdRP) was validated to silence a synthesised nsp12 RNA mimic in lung cell lines and function as an antifibrotic miR-27 in regulating target transcriptomes related to TGF-ß signalling. siRNA sequences with an antifibrotic miRNA-like activity that could synergistically treat COVID-19 are available online ( http://clip.korea.ac.kr/covid19 ).

AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.

Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs). The mi/siRNAs contain seed sequences (positions 2-7) of tumor-suppressive miRNAs while maintaining perfect sequence complementarity to the AGO-accessible tumor target sites. Initially, host miRNA interactions with human papillomavirus 18 (HPV18) were identified in cervical cancer by AGO CLIP, revealing tumor-suppressive activity of miR-1/206 and miR-218. Based on the AGO-miRNA binding sites, mi/siRNAs were designed to target E6 and E7 (E6/E7) transcript with seed sequences of miR-1/206 (206/E7) and miR-218 (218/E7). Synergistic anticancer activity of 206/E7 and 218/E7 was functionally validated and confirmed via RNA sequencing and in vivo xenograft models (206/E7). Other mi/siRNA sequences were additionally designed for cervical, ovarian, and breast cancer, and available as an online tool (http://ago.korea.ac.kr/misiRNA); some of the mi/siRNAs were validated for their augmented anticancer activity (206/EphA2 and 206/Her2). mi/siRNAs could coordinate miRNA-like activity with robust siRNA function, demonstrating the potential of AGO CLIP analysis for RNAi therapeutics.

Surveillance assessment for veterinary biocidal products in Korea: A laboratory investigation.

Veterinary biocides used in animal husbandry have the potential to cause human health concerns. Biocidal products for veterinary use, which contain pesticides approved in Korea, comprise 49 active ingredients within 234 products. Within 17 of these products there are 3 ingredients which are highly hazardous pesticides: coumaphos, dichlorvos and methomyl. In this study, the content of the active ingredients of 160 products sold domestically was investigated. Samples were collected for 119 biocidal products for veterinary use. These were analysed by high-performance liquid chromatography (HPLC) and gas chromatography (GC). Seventeen products were noncompliant (insufficient or excess quantity of active ingredients). The ingredients that were below the stated concentrations were amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, dichlorvos, fipronil, muscamone and trichlorfon. The ingredients that exceeded the stated concentrations were abamectin, fluvalinate and pyriproxyfen. The noncompliance rate in biocidal products for veterinary use was 9.19%. The results of this study show that three highly hazardous pesticides (coumaphos, dichlorvos and methomyl) and 10 active ingredients (abamectin, amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, fipronil, fluvalinate, muscamone, pyriproxyfen and trichlorfon) deviated from the stated concentrations. Thus, management plans should be established to ensure compliant veterinary drugs by post-distribution quality control, such as planning for regular inspection.

Position-specific oxidation of miR-1 encodes cardiac hypertrophy.

In pathophysiology, reactive oxygen species oxidize biomolecules that contribute to disease phenotypes1. One such modification, 8-oxoguanine2 (o8G), is abundant in RNA3 but its epitranscriptional role has not been investigated for microRNAs (miRNAs). Here we specifically sequence oxidized miRNAs in a rat model of the redox-associated condition cardiac hypertrophy4. We find that position-specific o8G modifications are generated in seed regions (positions 2-8) of selective miRNAs, and function to regulate other mRNAs through o8G•A base pairing. o8G is induced predominantly at position 7 of miR-1 (7o8G-miR-1) by treatment with an adrenergic agonist. Introducing 7o8G-miR-1 or 7U-miR-1 (in which G at position 7 is substituted with U) alone is sufficient to cause cardiac hypertrophy in mice, and the mRNA targets of o8G-miR-1 function in affected phenotypes; the specific inhibition of 7o8G-miR-1 in mouse cardiomyocytes was found to attenuate cardiac hypertrophy. o8G-miR-1 is also implicated in patients with cardiomyopathy. Our findings show that the position-specific oxidation of miRNAs could serve as an epitranscriptional mechanism to coordinate pathophysiological redox-mediated gene expression.

Result and Effectiveness of Malicious E-mail Response Training in a Hospital.

Malicious e-mails sent intentionally to institutions have caused an increase in data breaches. Measures against these methods must be taken by healthcare institutions to prevent leakage of sensitive personal medical information. As a form of training, we conducted a phishing simulation to gauge the response of the hospital staff to similar email attacks, and to raise awareness about information security protocols.

Chronological changes in rhinitis symptoms present in school-aged children with allergic sensitization.

INTRODUCTION: It is difficult to accurately predict the natural course of allergic rhinitis (AR), because it is affected by a wide variety of environmental influences, as well as genetic predisposition. Considering the high prevalence of allergic rhinitis in children and adolescents, caregivers should be given appropriate information regarding the disease course. This study aimed to understand the prognosis of allergic rhinitis by examining the relationship between allergic sensitization and rhinitis symptoms during this developmental period. METHODS: This cross-sectional study included 1069 children aged 9-16 years from the Korean International Study of Asthma and Allergies in Childhood Survey database who had completed health questionnaires, and for whom skin prick test results were available. Data were collected during May 2016. The distribution of sensitization and allergic symptoms was compared by age groups (elementary, middle, and high school). Data were analyzed using linear-by-linear analysis. RESULTS: Sensitization to at least one tested allergen differed by age (59.2%, 58.3%, 68.2%, in elementary, middle, and high school students, respectively; p = 0.025), and seasonal allergen sensitization (35.0%, 37.1%, 53.9%, respectively) increased with age (p < 0.001). Conversely, the proportion of rhinitis symptoms among sensitized children decreased as age increased (58.80%, 52.90%, 49.70%, respectively; p = 0.047). However, the rate of non-allergic rhinitis was age-independent. CONCLUSION: With increasing age during childhood and adolescence, symptomatic allergic rhinitis decreases; thus, subclinical allergic rhinitis increases. This suggests that the symptoms of later-sensitized children are less clearly manifested, or that the symptoms reduce as previously sensitized children mature. This should be clarified further in a longitudinal study.

The association between the parenting stress of the mother and the incidence of allergic rhinitis in their children.

OBJECTIVES: The prevalence of allergic rhinitis and the social burden related to the management of allergic rhinitis have persistently increased. There are many studies investigating the association between the allergic diseases of children and the stress of their parent. However, the relationship between parenting stress and the incidence of allergic rhinitis among children requires further investigation. We aimed to investigate the significance of parenting stress for mothers with children treated for allergic rhinitis. METHODS: The mothers of 250 children in the second and third grade of elementary school were involved in this study. The Parenting Stress Index-Short Form (PSI-SF) was used to measure parenting stress. Additionally, the monthly household income, treatment history for allergic diseases (atopic dermatitis, asthma, and allergic rhinitis) during the past 12 months, and maternal education status were investigated using the questionnaire. RESULTS: Parenting stress index score was significantly higher among the mothers of children treated for allergic rhinitis (76.41 ± 9.35) compared with the parents of children without treatment history for allergic rhinitis (70.06 ± 13.74). Nonetheless, there were no significant differences between the cases of children with atopic dermatitis and those with asthma. We analyzed the association between allergic rhinitis and parenting stress adjusted for the monthly household income, and maternal education status, and showed that a treatment history of allergic rhinitis was significantly associated with parenting stress (coefficient 7.477, 95% interval 1.703-13.252; p = 0.011). CONCLUSION: Treatment of the children for allergic rhinitis significantly affects the parenting stress of their mother. We recommend that mothers with children with allergic rhinitis should receive appropriate counseling about parenting stress.

Prevalence of Pseudoexfoliation Syndrome in an Isolated Island Population of Korea: The Woodo Study.

PURPOSE: To determine the prevalence and clinical characteristics of pseudoexfoliation syndrome (PXS) within Korean population living in Woodo Island. METHODS: Among the 625 residents aged 50 years or older, 305 residents (197 women and 108 men) participated in the study; a response rate of 48.8%. Participants filled out questionnaires on life style. Intraocular pressure and corneal endothelial cell function was measured. Both pupils were dilated. Fundus photographs and stereo disc photographs were taken. Vertical cup-to-disc ratio was determined. Pure tone audiometry threshold was measured at 0.5, 1, 2, 4, and 6 kHz of frequencies for each ear. RESULTS: The prevalence rate of PXS among Woodo Island residents older than 50 years significantly increased with age, from 1.0% [95% confidence interval (CI), 0%-2.8%] in participants aged 50 to 59 years to 23.3% (95% CI, 8.2%-38.5%) in those aged over 80 years (P<0.001). The prevalence of PXS showed no significant difference between men and women in all age groups. The age-standardized prevalence rate of PXS was 10.4% (95% CI, 8.0%-12.8%), with a rate of 9.4% (95% CI, 5.8%-13.1%) in men and 14.9% (95% CI, 11.3%-18.4%) in women. PXS did not show significant association with smoking, outdoor activity, and occupation, except alcohol consumption. PXS showed significant decrease in endothelial cell density. Pure tone audiometry test of PXS group revealed statistically significant decrease in 1, 2 kHz. CONCLUSIONS: The prevalence of PXS was 10.4% in the 50 years and older age group, and tended to increase with age. Decrease in corneal endothelial function and selective hearing loss was correlated in PXE patients, supporting impairment of systemic endothelial function in PXE syndrome.

Effect of Porcine Chondrocyte-Derived Extracellular Membrane (CDECM) on Postoperative Wound Healing in an Experimental Rabbit Model of Glaucoma Filtration Surgery.

PURPOSE: We investigated whether a chondrocyte-derived extracellular membrane (CDECM) could reduce postoperative scar formation in an experimental rabbit model of glaucoma filtration surgery. METHODS: Thirty-six male New Zealand white rabbits underwent experimental glaucoma filtration surgeries on the right eye and were randomly divided into the following two treatment groups: the CDECM group was treated with subconjunctival injections of 0.1ml CDECM (25 mg/ml; n = 18 eyes), and the operation (OP) group was treated with subconjunctival injections of 0.1 ml balanced salt solution (n = 18 eyes). The left eyes were used as controls (n = 36 eyes). The effects of the CDECM on the experimental rabbit model were investigated using histopathological, immunochemical analyses and Western blotting analyses of the inflammation, fibrosis and angiogenesis. RESULTS: On the 14th postoperative day, the eyes of the CDECM group displayed reduced vascularity and fibrosis compared with the OP group. The vascular endothelial growth factor (VEGF), CD31 and TNFß immunostaining were also reduced in the CDECM group. The level of TNFα mRNA was increased in the OP group. On the 28th postoperative day, the eyes of the CDECM group also exhibited reduced vascularity and less inflammation and fibrosis than those of the OP group. The expressions of VEGF, CD31, macrophage, TNFß and NF-κB p65 were also decreased in the CDECM group. The levels of TNFα mRNA significantly differ, and the level of matrix metallopeptidase 9 (MMP9) was increased in the OP group. To determine the specific upstream pathway that was associated with NF-κB activation due to glaucoma filtration surgery, we measured Akt, PKCs and MAPKs signaling. The phosphorylation of p38 MAPK was increased in the OP group, whereas this expression was decreased by CDECM treatment. CONCLUSIONS: CDECM seems to suppress angiogenesis, inflammation and fibrosis, which were related to wound healing in the experimental rabbit model of glaucoma filtration surgery. This effect, resulting from the inhibition of NF-κB expression, may be the blocking of the p38 MAPK signaling pathway.

Serum periostin level is not associated with allergic rhinitis or allergic sensitization in Korean children.

OBJECTIVES: Periostin is a matricellular protein, synthesized in the airway epithelium and induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of T helper type 2 cell (Th2)-induced airway inflammation, and as a measure of the response to Th2-targeted therapy, has recently been highlighted. We explored the relationship between serum periostin and allergic rhinitis in Korean children. METHODS: Data for fifth and sixth grade children from six randomly selected elementary schools located in Jeju and Seogwipo City, Korea, were investigated. Serum periostin levels were determined by enzyme-linked immunosorbent assay. Sex, school grade, body mass index, and presence of allergic nasal symptoms were obtained via a self-reported survey and skin prick testing was performed. RESULTS: There were no significant differences between groups, when stratification was applied according to sex, grade, presence of atopy, and presence of allergic nasal symptoms. Sex and body mass index were significantly associated with serum periostin levels in multivariate linear regression analysis. However, allergic rhinitis was not associated with serum periostin levels. CONCLUSION: Allergic rhinitis or allergic sensitization in Korean children did not influence serum periostin levels. Further studies are required to investigate the significance of serum periostin levels in pediatric allergic rhinitis.

[Development and Evaluation of Allergic Rhinitis-Specific Quality of Life (ARSQOL) Scale for Adults].

PURPOSE: The purpose of this study was to develop an Allergic Rhinitis-Specific Quality of Life (ARSQOL) scale and verify its validity and reliability. METHODS: ARSQOL was developed in 5 steps. Items for the preliminary instrument of ARSQOL were developed through a literature review and deep interviews with allergic rhinitis patients. Face validity with Content Validity Index (CVI), construct validity using factor analysis, and known group comparison, criterion validity test using correlation between ARSQOL and total nasal symptoms score (TNSS) were conducted to evaluate the validity of ARSQOL. Cronbach's α was used to evaluate the reliability of ARSQOL. RESULTS: CVI for the items in the final ARSQOL were .92. Five factors including discomfort associated with nasal symptoms (4 items), physical function (7 items), mental function (5 items), sleep disorder and social function (4 items), and problems of daily life (6 items) were identified through factor analysis and these five factors explained 66.6% of the total variance. The correlation coefficient between TNSS and the total score of life quality was -.69. In the group comparison, the persistent allergic rhinitis group showed lower ARSQOL scores than the intermittent patient group, and moderate to the severe allergic rhinitis patient group presented poorer ARSQOL than the mild symptom patient group. The Cronbach's α reliability coefficient was .95. CONCLUSION: Results show that the ARSQOL has good reliability and validity and thus ARSQOL is a useful scale for clinical practices and research as a measure of quality of life in adults with allergicr hinitis.

New allergen sensitization might be associated with increased body mass index in children.

BACKGROUND: Results of previous studies have shown a relationship between obesity and allergic diseases. However, concrete evidence about the association between obesity and allergies has been lacking. OBJECTIVE: The present study aimed to evaluate the potential association between body mass index (BMI) and the change in sensitization on skin-prick tests in children over a 2-year follow-up period. METHODS: Children in first and second grade from six elementary schools were recruited in 2010. The same participants, now in third and fourth grade, were recruited again in 2012. The enrolled children underwent skin-prick tests and physical examinations in 2010 and again in 2012. RESULTS: Four hundred fourteen children (boys to girls, 208 to 206) were included. Among 414 participants, 73 children showed new sensitization and 24 children showed negative conversion of allergic sensitization after 2 years. One hundred sixty-one children showed positive results on both tests, and 156 children showed negative results on both tests. The mean (standard deviation) change in BMI (1.09 ± 1.81 kg/m(2)) over a 2-year follow-up in newly sensitized children was significantly greater than that of other groups (p = 0.008). CONCLUSION: Children who became newly sensitized to allergens tended to exhibit significant increases in BMI. Therefore, further evaluation of the relationship between obesity and allergy is needed.

Association of serum eosinophilia and total immunoglobulin E concentration with the risk of allergic symptoms and allergic sensitization, respectively: A 2-year follow-up study.

OBJECTIVES: Serum eosinophil percentage (SEP), eosinophil cationic protein (ECP) concentration, and total IgE (TIgE) concentration are known to increase in patients with allergic disease; however, the relevance of these elevated markers in children with negative allergic test results remains unclear. Therefore, this 2-year follow-up study aimed to investigate whether SEP, ECP concentration, and TIgE concentration are associated with an increased risk for allergic sensitization and allergic symptoms. METHODS: In 2012, SEP, ECP concentration, and TIgE concentration of third- and fourth-grade students from 6 elementary schools were measured. Skin prick test was performed, and the presence of allergic nasal symptoms was investigated using a questionnaire. In 2014, the same examinations were performed in the same set of students, who were then in the fifth and sixth grades, respectively, of the same schools. The cut-off value and usefulness of serologic markers (eosinophil count, ECP concentration, and TIgE concentration) were calculated using the receiver operating characteristic curve. RESULTS: Serum eosinophil percentage (cut-off value, 3.8%) was associated with the newly developed allergic nasal symptoms (sensitivity, 77.9; specificity, 41.8). A high serum TIgE concentration (cut-off value, 17.7 IU/mL) was also associated with the risk for allergic sensitization (sensitivity, 46.3; specificity, 85.3). CONCLUSION: SEP and TIgE concentration were associated with the development of allergic symptoms and allergic sensitization, respectively, 2 years after the first examination.

Abasic pivot substitution harnesses target specificity of RNA interference.

Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼ 80-100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications.

Japanese Cedar (Cryptomeria japonica) Pollinosis in Jeju, Korea: Is It Increasing?

Jeju is an island in South Korea located in a temperate climate zone. The Japanese cedar tree (JC) has become the dominant tree species while used widely to provide a windbreak for the tangerine orchard industry. An increase in pollen counts precedes atopic sensitization to pollen and pollinosis, but JC pollinosis in Jeju has never been studied. We investigated JC pollen counts, sensitization to JC pollen, and JC pollinosis. Participants were recruited among schoolchildren residing in Jeju City, the northern region (NR) and Seogwipo City, the southern region (SR) of the island. The JC pollen counts were monitored. Sensitization rates to common aeroallergens were evaluated by skin prick tests. Symptoms of pollinosis were surveyed. Among 1,225 schoolchildren (49.6% boys, median age 13 years), 566 (46.2%) were atopic. The rate of sensitization to Dermatophagoides pteronyssinus (35.8%) was highest, followed by D. farinae (26.2%), and JC pollen (17.6%). In the SR, 156 children (23.8%) were sensitized to JC pollen; this rate was significantly higher than that in the NR (59 children, 10.4%, P<0.001). A significant increment in the sensitization rate for JC pollen with increasing school level was observed only in the SR. JC pollen season in the SR started earlier and lasted longer than that in the NR. JC pollen season in Jeju was defined as extending from late January to mid-April. The prevalence of JC pollinosis was estimated to be 8.5%. The prevalence differed significantly between the NR and SR (5.3% vs 11.3%, P<0.001), mainly due to the difference in sensitization rates. JC pollen is the major outdoor allergen for early spring pollinosis in Jeju. JC pollen season is from late January to mid-April. Warmer weather during the flowering season scatters more JC pollen in the atmosphere, resulting in a higher sensitization rate in atopic individuals and, consequently, making JC pollinosis more prevalent.

Multifunctional activity of polyphenolic compounds associated with a potential for Alzheimer's disease therapy from Ecklonia cava.

Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 µM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95 µM), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aß. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong ß-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease.

Association between serum mercury concentration and leukocyte differential count in children.

There have been a number of animal studies on the immunological effects of mercury. However, there is a lack of studies investigating the effects of mercury in children. We investigated the association between serum mercury and leukocyte differential count in Korean children. The relationship between mercury and leukocyte differential count (segment, lymphocyte, monocyte, basophil, and eosinophil counts) was analyzed by multivariate linear analysis adjusted for sex, BMI, parental smoking, lead, cadmium, and allergic sensitization in 311 children. Mercury showed a positive correlation with lymphocyte count (coefficient 113.8, 95% confidence interval 26.7-200.9). However, mercury was not associated with total leukocyte, segment, monocyte, basophil, or eosinophil count. Mercury was associated with the increased of lymphocyte count in Korean children. Further studies will be required to ascertain the clinical significance of this association.

Histamine skin reactivity increases with body mass index in Korean children.

OBJECTIVE: Histamine skin prick testing is most commonly used to diagnose immunoglobulin E (IgE)-mediated allergic diseases, and histamine reactivity is used as a standardized positive control in the interpretation of a skin prick test. However, reactivity to histamine differs among individuals for reasons that are poorly understood. The present study aimed to evaluate the potential association between body mass index (BMI) and histamine skin reactivity in children. METHODS: A total of 451 children (246 boys, 205 girls) aged 7-8 years were enrolled in this study. The skin prick test was performed with 26 aeroallergens commonly found in Korea. Other information was collected, including sex, age, BMI, parental allergy history, and parental smoking status. Multivariate analysis was used to confirm the association between histamine skin reactivity and BMI. RESULTS: The histamine wheal size was revealed to be associated with BMI (Spearman's Rho 0.161, p<0.001). This association was confirmed by multivariate analysis, after adjusting for sex, age, parental allergy history, parental smoking status, and allergic sensitization (coefficient B 0.071, 95% confidence interval 0.030-0.112). CONCLUSIONS: Skin responses to histamine were primarily correlated with increased BMI. Further studies are needed to understand the clinical implication of BMI when interpreting the results of skin prick test.