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The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) that applied herbal medicine to treat viral hepatitis B and C in order to determine the therapeutic efficacy of herbal medicine.EMBASE, Pubmed, NDSL, KMBASE, KISS, KISTI, Koreamed, Koreantk, and Oasis databases were searched to identify RCTs. The selected studies were assessed by the Cochrane group's risk of bias tool.A total of 15 RCTs were selected, and the hepatitis B virus (HBV) DNA reduction was significantly higher in patients treated with herbal medicine combined with Western medicine than in patients treated with herbal medicine. Herbal medicine combined with Western medicine was also superior to Western medicine alone in achieving hepatitis B e-antigen (HBeAg) and alanine aminotransferase [ALT] reduction. Only herbal medicine alone was not superior to Western medicine treatments in achieving HBV DNA, HBeAg, and ALT reduction.

Objective The aims of this study were to explore the prevalence of and identify predictors of anxiety and depression related to coronavirus disease of 2019 (COVID-19) in South Korea.Methods The analysis is based on a quota survey design and a sampling frame that permitted recruitment of a national sample of 1,014 individuals between March 17–31, 2020. Several standardized measurements were used, including GAD-7, PHQ-9, COVID-19 related fear, restrictions in deaily life, as well as sociodemographic information and physical and psychosocial needs during the pandemic. Multiple logistic regression was conducted to analyze the influence of sociodemographic factors, fear, and physical/psychosocial needs on anxiety and depression.Results Significant numbers of the respondents were identifiable anxiety (19.0%) and depression group (17.5%), respectively. This indicates that the depression and anxiety prevalence rate after the COVID-19 is substantially high compared to the depression rate of 2.6% in 2020 and 2.8% in 2018 both reported in the Korea Community Health Survey and the anxiety rate of 5.7% reported in 2016 Survey of Mental Disorders in Korea. Multiple logistic regression results showed age, COVID-19 related fear, and the level of restrictions in daily as significant factors in understanding and predicting the anxiety group. Likfewise, the COVID-19 related fear, restrictions in daily life, and need for economic support were important predictors in predicting the depression group.Conclusion Findings on predictors for greater vulnerability to anxiety and depression has important implications for public mental health in the context of the COVID-19 pandemic.

Intellectual disability (ID) is a heterogeneous clinical entity and includes an excess of males who harbor variants on the X-chromosome (XLID). We report rare FAM50A missense variants in the original Armfield XLID syndrome family localized in Xq28 and four additional unrelated males with overlapping features. Our fam50a knockout (KO) zebrafish model exhibits abnormal neurogenesis and craniofacial patterning, and in vivo complementation assays indicate that the patient-derived variants are hypomorphic. RNA sequencing analysis from fam50a KO zebrafish show dysregulation of the transcriptome, with augmented spliceosome mRNAs and depletion of transcripts involved in neurodevelopment. Zebrafish RNA-seq datasets show a preponderance of 3′ alternative splicing events in fam50a KO, suggesting a role in the spliceosome C complex. These data are supported with transcriptomic signatures from cell lines derived from affected individuals and FAM50A protein-protein interaction data. In sum, Armfield XLID syndrome is a spliceosomopathy associated with aberrant mRNA processing during development., Armfield X-linked disability (XLID) disorder has previously been linked to a locus in Xq28. Here, the authors report rare missense variants in FAM50A at Xq28, show that FAM50A interacts with the spliceosome, and that mis-splicing is enriched in knockout zebrafish suggesting it is a spliceosomopathy.

Isomaltooligosaccharides (IMOs) have good prebiotic effects, and long IMOs (LIMOs) with a degree of polymerization (DP) of 7 or above show improved effects. However, they are not yet commercially available, and require costly enzymes and processes for production. The Nterminal region of the thermostable Thermoanaerobacter thermocopriae cycloisomaltooligosaccharide glucanotransferase (TtCITase) shows cyclic isomaltooligosaccharide (CI)-producing activity owing to a catalytic domain of glycoside hydrolase (GH) family 66 and carbohydrate-binding module (CBM) 35. In the present study, we elucidated the activity of the C-terminal region of TtCITase (TtCITase-C; Met740-Phe1,559), including a CBM35-like region and the GH family 15 domain. The domain was successfully cloned, expressed, and purified as a single protein with a molecular mass of 115 kDa. TtCITase-C exhibited optimal activity at 40°C and pH 5.5, and retained 100% activity at pH 5.5 after 18-h incubation. TtCITase-C synthesized α-1,6 glucosyl products with over seven degrees of polymerization (DP) by an α-1,6 glucosyl transfer reaction from maltopentaose, isomaltopentaose, or commercialized maltodextrins as substrates. These results indicate that TtCITase-C could be used for the production of α-1,6 glucosyl oligosaccharides with over DP7 (LIMOs) in a more cost-effective manner, without requiring cyclodextran.

The LAMMER kinase in eukaryotes is a well-conserved dual-specificity kinase. Aspergillus species cause a wide spectrum of diseases called aspergillosis in humans, depending on the underlying immune status of the host, such as allergy, aspergilloma, and invasive aspergillosis. Aspergillus fumigatus is the most common opportunistic fungal pathogen that causes invasive aspergillosis. Although LAMMER kinase has various functions in morphology, development, and cell cycle regulation in yeast and filamentous fungi, its function in A. fumigatus is not known. We performed molecular studies on the function of the A. fumigatus LAMMER kinase, AfLkhA, and reported its involvement in multiple cellular processes, including development and virulence. Deletion of AflkhA resulted in defects in colonial growth, production of conidia, and sexual development. Transcription and genetic analyses indicated that AfLkhA modulates the expression of key developmental regulatory genes. The AflkhA-deletion strain showed increased production of gliotoxins and protease activity. When conidia were challenged with alveolar macrophages, enodocytosis of conidia by macrophages was increased in the AflkhA-deletion strain, resulting from changes in expression of the cell wall genes and thus content of cell wall pathogen-associated molecular patterns, including β-1,3-glucan and GM. While T cell-deficient zebrafish larvae were significantly susceptible to wild-type A. fumigatus infection, AflkhA-deletion conidia infection reduced host mortality. A. fumigatus AfLkhA is required for the establishment of virulence factors, including conidial production, mycotoxin synthesis, protease activity, and interaction with macrophages, which ultimately affect pathogenicity at the organismal level.

A supernatant solution of the silicate species extracted after alkali fusion of the acid-treated power plant fly ash was used to prepare mesoporous silica foams (MSFS) in acidic condition, where Pluronic P123 and trimethylbenzene (TMB) were used as the structure directing agent and swelling agent, respectively. The MSF was impregnated with polyethyleneimine (PEI) up to 63.2 wt.%, which exhibited CO2 adsorption capacity of 4.7 mmol/g adsorbent at 75 °C, 1 bar. Additionally, the MSF after ethylenediaminetetraacetic acid (EDTA) functionalization showed the Nd3+ adsorption capacity of 117 mg/g at the optimal pH of 6, with sufficiently fast kinetics and good recyclability.

The purpose of this study was to evaluate the changes of liver function test before and after treatment in patients admitted to Korean medicine hospital. We checked liver function test level (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin) of 147 patient who admitted in Korean medicine hospital from July 1, 2015 to June 30, 2018. The subjects were selected those who took herbal medicine continuously during the admission period and who performed liver function test on admission and before discharge. And the subjects were excluded those who had a history of liver and biliary disease at the time of admission or who took hepatoprotectants. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase significantly decreased compared with the values of admission(p 0.05). On admission 31 patients(21.1%) had abnormal liver function and 6 patients(4.1%) had liver injury while 19 patients(12.9%) had abnormal liver function and 6 patients(4.1%) showed liver injury before discharge. This study suggests that herbal medicine may not injure liver function.

Vanishing white matter (VWM) disease is a genetic leukodystrophy leading to severe neurological disease and early death. VWM is caused by bi-allelic mutations in any of the five genes encoding the subunits of the eukaryotic translation factor 2B (EIF2B). Previous studies have attempted to investigate the molecular mechanism of VWN by constructing models for each subunit of EIF2B that causes VWM disease. The underlying molecular mechanisms of the way in which mutations in EIF2B3 result in VWM are largely unknown. Based on our recent results, we generated an eif2b3 knockout (eif2b3−/−) zebrafish model and performed quantitative proteomic analysis between the wild-type (WT) and eif2b3−/− zebrafish, and identified 25 differentially expressed proteins. Four proteins were significantly upregulated, and 21 proteins were significantly downregulated in eif2b3−/− zebrafish compared to WT. Lon protease and the neutral amino acid transporter SLC1A4 were significantly increased in eif2b3−/− zebrafish, and crystallin proteins were significantly decreased. The differential expression of proteins was confirmed by the evaluation of mRNA levels in eif2b3−/− zebrafish, using whole-mount in situ hybridization analysis. This study identified proteins which candidates as key regulators of the progression of VWN disease, using quantitative proteomic analysis in the first EIF2B3 animal model of VWN disease.

Copper has demonstrated utility in multiple industrial applications for its high conductivity and antibacterial/antiviral properties. However, numerous findings have suggested potential hazards regarding pathogenesis. This study was conducted to demonstrate the application of zebrafish (Danio rerio) as a cost-effective biological assay to detect environmental pollution, i.e., heavy metal of coins. We demonstrated that zebrafish larvae exposed to copper-plated coins or copper (II) ion solution elicited a consistent phenotype of early mortality without signs of morphological defects in surviving individuals. Copper ion solution served as a standard to (1) corroborate copper exposure from coins and (2) demonstrate proportional increase in early mortality phenotype according to concentration. We found that 5 μM CuSO4·5H2O was the minimal concentration to elicit the observed phenotypes from copper toxicity. This study aimed to demonstrate how a simple protocol involving wild-type zebrafish larvae could provide an economical solution to water monitoring in areas of rapid technological advancement and increasing environmental concerns, especially in communities without access to expensive analytical methods.

The dramatic changes in people’s daily lives caused by the 2019 coronavirus (COVID-19) pandemic have had a huge impact on their emotions and behaviors. This study aimed to examine psychosocial responses to COVID-19 using network analysis. A total of 1,500 urban residents of South Korea, selected from an online public panel, were surveyed using self-rating questionnaires addressing daily life changes, fear of infection, and distress related to COVID-19. Participants also completed a 10-item Perceived Stress Scale survey. We constructed regularized partial correlation networks, estimated global and local network metrics, tested network accuracy and stability, and compared the estimated networks between men and women. The network of the psychosocial responses consisted of 24 nodes that were classified into five groups: ‘fear of infection’, ‘difficulty with outside activities’, ‘economic loss’, ‘altered eating and sleeping’, and ‘adaptive stress’. The node centralities indicated that ‘distress in obtaining daily necessities’ and ‘concern about harming others’ were the most important issues in people’s responses to COVID-19. These nodes were connected by a negative edge, reflecting individual- and community-level issues, respectively. The overall level of perceived stress was linked to the network by the connection node ‘anger toward others or society’, which was associated with economic problems in men, but with distress from changes in daily activities in women. The results suggest that two contrasting feelings—personal insecurity regarding basic needs and a collectivistic orientation—play roles in the response to unusual experiences and distress due to COVID-19. This study also showed that public anger could arise from the psychological stress under the conditions imposed by COVID-19.

Leukodystrophy with vanishing white matter (VWM), also called Childhood Ataxia with Central Nervous System Hypomyelination, is caused by mutations in the subunits of the eukaryotic translation initiation factor, EIF2B1, EIF2B2, EIF2B3, EIF2B4 or EIF2B5. However, little is known regarding the underlying pathogenetic mechanisms, and there is no curative treatment for VWM. In this study, we established the first EIF2B3 animal model for VWM disease in vertebrates by CRISPR mutagenesis of the highly conserved zebrafish ortholog eif2b3. Using CRISPR, we generated two mutant alleles in zebrafish eif2b3, 10- and 16-bp deletions, respectively. The eif2b3 mutants showed defects in myelin development and glial cell differentiation, and increased expression of genes in the induced stress response pathway. Interestingly, we also found ectopic angiogenesis and increased VEGF expression. Ectopic angiogenesis in the eif2b3 mutants was reduced by the administration of VEGF receptor inhibitor SU5416. Using the eif2b3 mutant zebrafish model together with in silico protein modeling analysis, we demonstrated the pathogenicity of 18 reported mutations in EIF2B3, as well as of a novel variant identified in a 19-month-old female patient: c.503 T > C (p.Leu168Pro). In summary, our zebrafish mutant model of eif2b3 provides novel insights into VWM pathogenesis and offers rapid functional analysis of human EIF2B3 gene variants.

A series of aminated- (1–9) and sulfonamide-containing diarylpentadienones (10–18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10–18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.

Background We examined the effects of mass media usage on people's level of knowledge about coronavirus disease 2019 (COVID-19), fear of infection, prejudice towards infected people, and anxiety level. In addition, we investigated whether knowledge about COVID-19 can reduce fear, prejudice, and anxiety. Methods We performed an anonymous online survey in 1,500 residents aged 19–65 years between April 24 and May 5 of 2020. Anxiety level was assessed using the generalized anxiety disorder-7 scale. We used a questionnaire to investigate COVID-19-related media use, knowledge about COVID-19, fear of infection, and prejudice towards infected people. We analyzed the relationships among the variables using the structural equation model. Results Media use had significant effects on fear of infection, prejudice against infected people, and anxiety. Knowledge about COVID-19 had a significant protective effect on fear of infection, prejudice against infected people, and anxiety. However, the effect of media use on knowledge about COVID-19 was not statistically significant. There was a partial mediating effect of prejudice against infected people and fear of infection on media usage and anxiety. Conclusion Our study demonstrated significant effects of mass media coverage regarding COVID-19 on fear, prejudice, and anxiety. While knowledge about COVID-19 could decrease fear, prejudice, and anxiety, the use of mass media did not enhance this knowledge. Medical societies should guide mass media reporting of COVID-19 and provide appropriate public education., Graphical Abstract

A facultatively anaerobic, Gram-stain-positive, catalase-negative, rod-shaped lactic acid bacterium, designated SG816T, was isolated from small intestine of a swine. Optimal growth occurred at 37 °C and pH 7.0. Furthermore, growth occurred in NaCl up to 0.5 % (w/v) but not at levels of salinity higher than 1 %. Comparative 16S rRNA gene sequencing and the matrix-associated laser desorption/ionization–time-of-flight mass spectometry profiling showed that strain SG816T was closely related to Lactobacillus delbrueckii subsp. bulgaricus KCTC 3635T (95.9 %) and Lactobacillus delbrueckii subsp. indicus JCM 15610T (95.9 %), followed by other Lactobacillus delbrueckii subspecies (95.9–95.7 %) and Lactobacillus equicursoris DSM 19284T (95.6 %). A comparison of two housekeeping genes, RNA polymerase alpha subunit (rpoA) and phenylalanyl-tRNA synthase alpha subunit (pheS), revealed that strain SG816T formed a separate branch within the clade of the genus Lactobacillus . The DNA G+C content level of the strain SG816T was 51.5 mol%. The strain was homofermentative and produced d-lactic acid from glucose fermentation. The major cellular fatty acids (>10 %) of the isolate were C18 : 1ω9c and C16 : 0. The peptidoglycan type was A4α l-Lys-d-Asp. On the basis of distinct phenotypic and phylogenetic properties, strain SG816T represents a novel species of the genus Lactobacillus , for which the name Lactobacillus porci sp. nov. is proposed. The type strain is SG816T (=KCTC 21090T=NBRC 112917T).

Background The demand for anti-melanogenic agents is increasing due to the unwanted side effects of current treatments. To find an effective anti-melanogenic agent, we used zebrafish as a whole animal model for phenotype-based drug and cosmetic discovery screening. Objectives The aim of this study was to identify and explore a small molecule that could be used for skin-whitening cosmetics. Methods Using zebrafish embryos, we examined the effects of 1000 compounds on zebrafish development and pigmentation. Pigmentation production was assessed by tyrosinase (TYR) enzymatic activity and melanin contents. Pigmentation marker expression in the human melanoma cell line HMV-II was analyzed by western blot. We also tested reconstituted human skin tissue and analyzed KDZ-001 with computational molecular modeling. Results We identified three compounds that affected the pigmentation of developing melanophores in zebrafish. Among them, we identified KDZ-001, a novel anti-melanogenic agent, which strongly inhibits melanin synthesis in the developing melanophores of zebrafish, HMV-II cells, and reconstituted human skin with no toxicity. We found that KDZ-001 directly inhibits TYR enzymatic activity. Notably, computational molecular modeling of KDZ-001 suggested that its interaction with copper ions in the active site of TYR is essential for melanin synthesis, further demonstrating that KDZ-001 mainly acts as a TYR inhibitor to synthesize melanin. Conclusion KDZ-001 inhibits melanin synthesis and has a potential for use in skin-whitening cosmetics.

The objective of this study was to evaluate the permeability of small molecules into the brain via the blood–brain barrier in zebrafish and to investigate the possibility of using this animal model as a screening tool during the early stages of drug discovery. Fifteen compounds were used to understand the permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma concentration was compared between the two animal models. The partition coefficient (Kp,brain), estimated using the concentration ratio at designated times (0.167, 0.25, 0.5, or 2 h) after oral administrations (per os, p.o), ranged from 0.099 to 5.68 in zebrafish and from 0.080 to 11.8 in mice. A correlation was observed between the Kp,brain values obtained from the zebrafish and mice, suggesting that zebrafish can be used to estimate Kp,brain to predict drug penetration in humans. Furthermore, in vivo transport experiments to understand the permeability glycoprotein (P-gp) transporter-mediated behavior of loperamide (...

Background Hearing Aids amplify sounds at certain frequencies to help patients, who have hearing loss, to improve the quality of life. Variables affecting hearing improvement include the characteristics of the patients’ hearing loss, the characteristics of the hearing aids, and the characteristics of the frequencies. Although the two former characteristics have been studied, there are only limited studies predicting hearing gain, after wearing Hearing Aids, with utilizing all three characteristics. Therefore, we propose a new machine learning algorithm that can present the degree of hearing improvement expected from the wearing of hearing aids. Methods The proposed algorithm consists of cascade structure, recurrent structure and deep network structure. For cascade structure, it reflects correlations between frequency bands. For recurrent structure, output variables in one particular network of frequency bands are reused as input variables for other networks. Furthermore, it is of deep network structure with many hidden layers. We denote such networks as cascade recurring deep network where training consists of two phases; cascade phase and tuning phase. Results When applied to medical records of 2,182 patients treated for hearing loss, the proposed algorithm reduced the error rate by 58% from the other neural networks. Conclusions The proposed algorithm is a novel algorithm that can be utilized for signal or sequential data. Clinically, the proposed algorithm can serve as a medical assistance tool that fulfill the patients’ satisfaction.

Ocular pathologic angiogenesis is an important causative risk factor of blindness in retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular macular degeneration. Guibi-tang (GBT) is a frequently used oriental herbal formula in East Asian countries, and is also called Qui-pi-tang in Chinese and Kihi-To in Japanese. In the present study, we investigated the preventive effect of GBT on retinal pathogenic neovascularization in a mouse model of oxygen-induced retinopathy (OIR). C57BL/6 mice were exposed to 75% hyperoxia for five days on postnatal day 7 (P7). The mice were then exposed to room air from P12 to P17 to induce ischemic proliferative retinopathy. GBT (50 or 100 mg/kg/day) was intraperitoneally administered daily for five days (from P12 to P16). On P17, Retinal neovascularization was measured on P17, and the expression levels of 55 angiogenesis-related factors were analyzed using protein arrays. GBT significantly decreased retinal pathogenic angiogenesis in OIR mice, and protein arrays revealed that GBT decreased PAI-1 protein expression levels. Quantitative real-time PCR revealed that GBT reduced vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and plasminogen activator inhibitor 1 (PAI-1) mRNA levels in OIR mice. GBT promotes potent inhibitory activity for retinal neovascularization by decreasing VEGF, FGF2, and PAI-1 levels.

A strictly anaerobic, Gram-stain-positive, catalase-negative, non-motile, rod-shaped bacterium, designated SG0102T, was isolated from the small intestine of a swine. Optimal growth occurred at 37°C and pH 7.0. Furthermore, growth was observed in the presence of up to 3% (w/v) NaCl but not at salinity levels higher than 4%. The comparative analysis of 16S rRNA gene sequences showed that strain SG0102T was most closely related to Kandleria vitulina DSM 20405T (93.3%), followed by Catenibacterium mitsuokai KCTC 5053T (91.1%), Sharpea azabuensis KCTC 15217T (91.0%), and Eggerthia catenaformis DSM 5348T (89.6%). The average nucleotide identity values between strain SG0102T and related species, K. vitulina DSM 20405T, C. mitsuokai KCTC 5053T, S. azabuensis KCTC 15217T, and E. catenaformis DSM 5348T, were 71.0, 69.3, 70.0, and 69.2%, respectively. The phylogenetic analysis based on 16S rRNA gene sequence revealed that strain SG0102T belonged to the family Erysipelotrichaceae in the class Erysipelotrichia. The DNA G + C content of the strain SG0102T was 39.5 mol%. The major cellular fatty acids (> 10%) of strain SG0102T were C16:0, C16:0 dimethyl acetal, and C18:2ω9/12c. The cell wall peptidoglycan of strain SG0102T contained the meso-diaminopimelic acid. The strain SG0102T produced lactic acid as a major end product of fermentation. These distinct phenotypic and phylogenetic properties suggest that strain SG0102T represents a novel species in a novel genus of the family Erysipelotrichaceae, for which the name Intestinibaculum porci gen. nov. sp. nov. is proposed. The type strain is SG0102T (= KCTC 15725T = NBRC 113396T).

Background and Purpose Although a variety of animal models have been used to test drug candidates and examine the pathogenesis of diabetic retinopathy, time-saving and inexpensive models are still needed to evaluate the increasing number of therapeutic approaches. Experimental Approach We developed a model for diabetic retinopathy using the early stage of transgenic zebrafish (flk:EGFP) by treating embryos with 130 mM glucose, from 3-6 days post fertilisation (high-glucose model). On day 6, lenses from zebrafish larvae were isolated and treated with 3% trypsin, and changes in hyaloid-retinal vessels were analysed using fluorescent stereomicroscopy. In addition, expression of tight junction proteins (such as zonula occludens-1), effects of hyperosmolar solutions and of hypoxia, and Vegf expression were assessed by RT –PCR. NO production was assessed with a fluorescent substrate. Effects of inhibitors of the VEGF receptor, NO synthesis and a VEGF antibody (ranibizumab) were also measured. Key Results In this high-glucose model, dilation of hyaloid-retinal vessels, on day 6, was accompanied by morphological lesions with disruption of tight junction proteins, overproduction of Vegf mRNA and increased NO production. Treatment of this high-glucose model with an inhibitor of VEGF receptor tyrosine kinase or an inhibitor of NO synthase or ranibizumab decreased dilation of hyaloid-retinal vessels. Conclusions and Implications These findings suggest that short-term exposure of zebrafish larvae to high-glucose conditions could be used for screening and drug discovery for diabetic retinopathy and particularly for disorders of retinal vessels related to disruption of tight junction proteins and excessive VEGF and NO production.

Choroidal neovascularization (CNV) is a common pathology in age-related macular degeneration. In this study, we evaluated in a rat model the effect of an extract of Cinidium officinale Makino and its bioactive compound, butylidenephthalide, on laser-induced CNV. Experimental CNV was induced in Long-Evans rats by laser photocoagulation. C. officinale extract (COE) and butylidenephthalide was intraperitoneally injected once per day for ten days after laser photocoagulation. Choroidal flat mounts were prepared to measure CNV areas and macrophage infiltration. We used a protein array to evaluate the expression levels of angiogenic factors. The CNV area and macrophage infiltration in COE-treated rats were significantly lower than in vehicle-treated rats. COE decreased the expression levels of IGFBP-1, MCP-1, PAI-1, and VEGF. Additionally, butylidenephthalide also inhibited the laser-induced CNV formation and macrophage infiltration and down-regulated the expression of IGFBP-1, MCP-1 and VEGF. These results suggest that COE exerts anti-angiogenic effects on laser-induced CNV by inhibiting the expression of IGFBP-1, MCP-1, and VEGF, indicating that anti-angiogenic activities of COE may be in part due to its bioactive compound, butylidenephthalide.

In this paper, we propose an improved filter selection method using Welch's t-test based on discriminative filter bank common spatial pattern (DFBCSP). Existing DFBCSP used the Fisher ratio in order to find out discriminative filters. However, the Fisher ratio can be used to know only comparative value of distinguishability but may not become a meaningful criterion to reject null hypothesis. As a reasonable alternative, we have introduced the Welch's t-test to find out not only contributory but also redundant filters used to classify features efficiently. Experimental results show that the classification accuracy increased by 1.28% on average when using the proposed filter selection method. 

DNA methylation is an epigenetic event that involves adding a methyl group to the cytosine (C) site, especially the one that pairs with a guanine (G) site (ie, CG or CpG site), in a human genome. This event plays an important role in both cancerous and normal cell development. Previous studies often assume symmetric methylation on both DNA strands. However, asymmetric methylation, or hemimethylation (methylation that occurs only on 1 DNA strand), does exist and has been reported in several studies. Due to the limitation of previous DNA methylation sequencing technologies, researchers could only study hemimethylation on specific genes, but the overall genomic hemimethylation landscape remains relatively unexplored. With the development of advanced next-generation sequencing techniques, it is now possible to measure methylation levels on both forward and reverse strands at all CpG sites in an entire genome. Analyzing hemimethylation patterns may potentially reveal regions related to undergoing tumor growth. For our research, we first identify hemimethylated CpG sites in breast cancer cell lines using Wilcoxon signed rank tests. We then identify hemimethylation patterns by grouping consecutive hemimethylated CpG sites based on their methylation states, methylation “M” or unmethylation “U.” These patterns include regular (or consecutive) hemimethylation clusters (eg, “MMM” on one strand and “UUU” on another strand) and polarity (or reverse) clusters (eg, “MU” on one strand and “UM” on another strand). Our results reveal that most hemimethylation clusters are the polarity type, and hemimethylation does occur across the entire genome with notably higher numbers in the breast cancer cell lines. The lengths or sizes of most hemimethylation clusters are very short, often less than 50 base pairs. After mapping hemimethylation clusters and sites to corresponding genes, we study the functions of these genes and find that several of the highly hemimethylated genes may influence tumor growth or suppression. These genes may also indicate a progressing transition to a new tumor stage.

The extraction and separation of aloe emodin were optimized via selective molecularly imprinted solid-phase extraction. Molecularly imprinted polymer was prepared from the functional monomer, methacrylic acid and a mixture of ethanol/dodecanol(90/10, volume ratio) as porogen. It overcomes the common problems of imprinting biological polar compounds and shows high selectivity compared favorably with those of non-imprinted polymer and commercially available C18 and silica cartridges in similar aloe emodin tests. Good linearity was obtained between 0.002 and 2.5 mg/mL (r2=0.998) with relative standard deviations below 3.3%.

The purpose of this study was to examine the effectiveness of aromatherapy with ginger essential oil on nausea and vomiting in abdominal surgery patients.This was a quasi-experimental study with a nonequivalent control group and repeated measures. The experimental group (n = 30) received ginger essential oil inhalation. The placebo control group (n = 30) received normal saline inhalation. The level of postoperative nausea and vomiting was measured using a Korean version of the Index of Nausea, Vomiting, and Retching (INVR) at baseline and at 6, 12, and 24 h after aromatherapy administration. The data were collected from July 23 to August 22, 2012.Nausea and vomiting scores were significantly lower in the experimental group with ginger essential oil inhalation than those in the placebo control group with normal saline. In the experimental group, the nausea and vomiting scores decreased considerably in the first 6 h after inhaled aromatherapy with ginger essential oil.Findings indicate that ginger essential oil inhalation has implications for alleviating postoperative nausea and vomiting in abdominal surgery patients.

Background: Retinal neovascularization, which is the pathological growth of new blood vessels, is associated with retinopathy of prematurity, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. In this study, we evaluated the effect of an extract of Cnidium officinale Makino (COE) and its bioactive compound, butylidenephthalide (BP), on the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and on retinal pathogenic neovascularization in the oxygen-induced retinopathy (OIR) mouse model. Method: The HUVECs were incubated with COE and BP (0.1-10 mu g/ml). The mice were exposed to 75 % oxygen for 5 days starting on the 7th postnatal day (P7-P12). Then, the mice were returned to room air and intraperitoneally injected with COE (100 mg/kg) and BP (5 mg/kg) once per day for 5 days (P12-P16). On P17, we measured retinal neovascularization and analyzed the angiogenesis-related proteins expression using protein arrays. Results: COE and BP inhibit the HUVECs migration and the tube formation in a dose-dependent manner. In addition, COE significantly decreased retinal neovascularization in the OIR mice. COE reduced the expression levels of AREG, ANG, DLL4, Endostatin, IGFBP-2 and VEGF. Additionally, BP also inhibited the retinal neovascularization and down-regulated the expression of AREG, ANG, DLL4 and VEGF. Conclusion: These results suggest that COE and BP exerts antiangiogenic effects on retinal neovascularization by inhibiting the expression of AREG, ANG, DLL4 and VEGF, indicating that antiangiogenic activities of COE may be in part due to its bioactive compound, BP.

A brain computer interface (BCI) system is to control a computer using bio-signals measured in brain. A P300 speller is one of electroencephalogram (EEG)-based BCI systems. The speller is to display target characters which are what a subject wants to enter by detecting P300 wave. To detect the wave, a lot of EEG signals were averaged over the whole signals to increase the signal-to-noise ratio and the support vector machine (SVM) was applied to a P300 speller to separate EEG signals with P300 wave and without P300 wave in previous works. In current classifier topics, there are some methods to average some classifiers for performance improvement. An ensemble of SVMs is one of them but it has enormous computational complexity. To overcome this computational burden, we propose a P300 speller with preprocessing of channel selection and non-target data reduction. In conclusion, the calculation speed becomes higher than conventional method but, as a feature dimension decreases in channel selection part of the proposed method, the accuracy of the proposed method is lowered in both subjects.

The adsorption behaviours of caffeine and theophylline on different metal-organic frameworks were examined by comparing their adsorption isotherms. Among C 18 , UIO-66, UIO-66-NH 2 and MIL-125-NH 2 , UIO-66 showed the highest amount of adsorption of target compounds (i.e. caffeine and theophylline). The maximum adsorbed amounts of caffeine and theophylline on UIO-66 were 0.451 and 0.392 mg, respectively. The experimental parameters in the equilibrium isotherms were estimated by linear and non-linear regression analyses. The adsorption equilibrium data of caffeine and theophylline were investigated using the following four models: linear, Langmuir, Freundlich and Langmuir–Freundlich models. Of these models, the Langmuir–Freundlich model showed the best fit. The regression coefficients (r 2 ) of the Langmuir–Freundlich model for adsorption of caffeine and theophylline on UIO-66 were 0.976 and 0.989, respectively.

AIM: To determine if growth arrest-specific 6 (Gas6) plays an important role in the regulation of angiogenesis in human retinal microvascular endothelial cells (HRMECs) and in vessel development of zebrafish. METHODS: Proliferation, wound-healing cell migration, and tube formation were measured in HRMECs treated with recombinant human Gas6 (rhGas6). Sprague-Dawley rat aortas in Matrigels were treated with rhGas6, and microvessel sprouting emanating from arterial rings was analyzed. Transgenic zebrafish embryos (flk:GFP) were microinjected with rhGas6 at 50 hours post-fertilization (hpf), and ectopic sprouting of subintestinal vessels (SIVs) was observed under a confocal microscope. Morpholino oligonucleotides (MOs) were microinjected to knockdown gas6 in zebrafish embryos, and intersegmental vessel impairment was observed. The effect of the extracellular signal-regulated kinase (ERK1/2) inhibitor on the migration of HRMECs and on vessel development in zebrafish embryos was tested. RESULTS: rhGas6 stimulated proliferation, migration, and tube formation in HRMECs in a dose-dependent manner. In rat aortas, rhGas6 induced vessel outgrowth, and the sprouting length was longer than that of controls. The rhGas6-microinjected zebrafish embryos had significantly increased vessel outgrowth in the SIVs. Recombinant human vascular endothelial growth factor (rhVEGF) served as a positive control. Knockdown of gas6 inhibited angiogenesis in the developing vessels of zebrafish. The ERK1/2 inhibitor inhibited HRMEC migration and intersegmental vessel formation in zebrafish embryos. CONCLUSIONS/INTERPRETATIONS: These data suggest that Gas6 plays a pivotal role in proliferation, migration, and sprouting of angiogenic endothelial cells in the retina and in zebrafish embryos. Furthermore, Gas6 induced angiogenic processes are induced via phosphorylation of ERK1/2.

A brain computer interface (BCI) system is to control a computer using bio-signals measured in brain. A P300 speller is one of electroencephalogram (EEG)-based BCI systems. The speller is to display target characters which are what a subject wants to enter. P300 wave, which is the most positive peak 260-410ms in an EEG signal after stimulus onset, is used as a control signal of the speller. The P300 wave has been separated using a blind source separation method in the existing P300 spellers. However, the conventional methods could not separate a source signal with Gaussian distribution from a set of mixed signals. To overcome this problem, we apply a kernel independent component analysis algorithm to P300 speller. The algorithm can successfully extract P300 component from a mixed signal even when it has source signals with nearly Gaussian distribution. In conclusion, the proposed P300 speller has 100% accuracy with less training signals and finds a target character more quickly than the conventional method.

Objective: This study investigated the effects of the balanced incline shoes on the stabilized walking, fatigue reduction, improvement of blood circulation and prevention of foot related disease for the pregnant women. Methods: The seven 7~9 month pregnant women and three maternities within 3 months after delivery without a history of disease performed the cycles for each of the two walking conditions: wearing balanced incline shoes and flat shoes. The differences between the two walking conditions were statistically investigated including three dimensional motion analysis, footprint pressures and blood flow. To find out any possible difference between these two kinds and among the subjects, the statistical tool was utilized with one-way layout design. Results: Of 10 subjects, seven subjects showed the significantly decreased in distance of both knee with balanced incline shoes than flat shoes (P 600 µm/sec) or B (400~600 µm/sec) after they put them on, indicating 1~2 part equivalent improvement. The blood stream velocity showed a incremental tendency after wearing balanced incline shoes. Conclusion: This result suggests that the balanced incline shoes corrected the postures, stabilized the gait pattern, decreased the excessive load on ankle plantar flexors, reduced the fatigue level and improved the blood circulation.