377 research outputs found

    Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

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    Carnosic acid (CA) is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS) and retinoic acid (RA). In addition, CA blocked the release of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2) from RAW264.7 cells activated by the toll-like receptor (TLR)-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN) and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS). CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF)-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K), Akt, inhibitor of κBα (IκBα) kinase (IKK), and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties

    Crystal structure of Helicobacter pylori MinE, a cell division topological specificity factor

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    In Gram-negative bacteria, proper placement of the FtsZ ring, mediated by nucleoid occlusion and the activities of the dynamic oscillating Min proteins MinC, MinD and MinE, is required for correct positioning of the cell division septum. MinE is a topological specificity factor that counters the activity of MinCD division inhibitor at the mid-cell division site. Its structure consists of an anti-MinCD domain and a topology specificity domain (TSD). Previous NMR analysis of truncated Escherichia coli MinE showed that the TSD domain contains a long α-helix and two anti-parallel β-strands, which mediate formation of a homodimeric α/β structure. Here we report the crystal structure of full-length Helicobacter pylori MinE and redefine its TSD based on that structure. The N-terminal region of the TSD (residues 19–26), previously defined as part of the anti-MinCD domain, forms a β-strand (βA) and participates in TSD folding. In addition, H. pylori MinE forms a dimer through the interaction of anti-parallel βA-strands. Moreover, we observed serial dimer–dimer interactions within the crystal packing, resulting in the formation of a multimeric structure. We therefore redefine the functional domain of MinE and propose that a multimeric filamentous structure is formed through anti-parallel β-strand interactions

    High frequencies of Y-chromosome haplogroup O2b-SRY465 lineages in Korea: a genetic perspective on the peopling of Korea

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    <p>Abstract</p> <p>Background</p> <p>Koreans are generally considered a Northeast Asian group, thought to be related to Altaic-language-speaking populations. However, recent findings have indicated that the peopling of Korea might have been more complex, involving dual origins from both southern and northern parts of East Asia. To understand the male lineage history of Korea, more data from informative genetic markers from Korea and its surrounding regions are necessary. In this study, 25 Y-chromosome single nucleotide polymorphism markers and 17 Y-chromosome short tandem repeat (Y-STR) loci were genotyped in 1,108 males from several populations in East Asia.</p> <p>Results</p> <p>In general, we found East Asian populations to be characterized by male haplogroup homogeneity, showing major Y-chromosomal expansions of haplogroup O-M175 lineages. Interestingly, a high frequency (31.4%) of haplogroup O2b-SRY465 (and its sublineage) is characteristic of male Koreans, whereas the haplogroup distribution elsewhere in East Asian populations is patchy. The ages of the haplogroup O2b-SRY465 lineages (~9,900 years) and the pattern of variation within the lineages suggested an ancient origin in a nearby part of northeastern Asia, followed by an expansion in the vicinity of the Korean Peninsula. In addition, the coalescence time (~4,400 years) for the age of haplogroup O2b1-47z, and its Y-STR diversity, suggest that this lineage probably originated in Korea. Further studies with sufficiently large sample sizes to cover the vast East Asian region and using genomewide genotyping should provide further insights.</p> <p>Conclusions</p> <p>These findings are consistent with linguistic, archaeological and historical evidence, which suggest that the direct ancestors of Koreans were proto-Koreans who inhabited the northeastern region of China and the Korean Peninsula during the Neolithic (8,000-1,000 BC) and Bronze (1,500-400 BC) Ages.</p

    Extreme Drug Resistance in Acinetobacter baumannii Infections in Intensive Care Units, South Korea

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    BACKGROUND: Difference in adaptability responses to stress has been observed amongst bird species, strains, and individuals. Components of the HPA axis, one of the internal systems involved in homeostasis re-establishment following stress, could play a role in this variability of responses. The aim of the present study was 1) to identify genes involved in the regulation of adrenal activity following ACTH stimulation and 2) to examine adrenal genes differentially expressed in individuals with high and low plasma corticosterone response following ACTH treatment. RESULTS: Analysis with 21 K poultry oligo microarrays indicated that ACTH treatment affected the expression of 134 genes. Several transcripts assigned to genes involved in the adrenal ACTH signaling pathway and steroidogenic enzymes were identified as differentially expressed by ACTH treatment. Real-time PCR on 18 selected genes confirmed changes in transcript levels of 11 genes, including MC2R, CREM, Cry, Bmal1, Sqle, Prax1, and StAR. Only 4 genes revealed to be differentially expressed between higher and lower adrenal responders to ACTH treatment. CONCLUSION: The results from the present study reveal putative candidate genes; their role in regulation of adrenal functions and adaptability to stress should be further investigated

    Performance Evaluation of the GlucoDr Plus Glucometer

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    Background: Because strict glucose control is important for reducing the complications of diabetes, the self-monitoring of blood glucose is one of the fundamental treatment modalities. Many glucometers have been developed. In the present study, we evaluated a new glucometer: GlucoDr (TM) Plus (Allmedicus, Anyang, Gyeonggi-do, Republic of Korea). Methods: The evaluation was performed based on Clinical and Laboratory Standards Institute guidelines. Interferences by ascorbic acid, uric acid, maltose, and acetaminophen were examined, and the performance of the unit was compared to those of six other glucometers. The effects of hematocrit, of oxygen partial pressure (PaO(2)), and of multiple users were also evaluated. Results: Within-run, between-run, between- day, and total imprecision (coefficients of variation) were 0.99-4.98%. Satisfactory linearity was found for glucose concentrations of 32.5-786.5 mg/dL (R(2) = 0.9985). A comparison with the reference laboratory method showed close concordance over the entire range of concentrations evaluated (R(2) = 0.9869). No significant effects were noted due to added interferents, hematocrit, and PaO(2). Conclusions: The GlucoDr Plus showed acceptable performance in terms of precision and linearity. It was minimally affected by various interferents. GlucoDr Plus is suitable for the self-monitoring of blood glucose by patients with diabetes.Schleis TG, 2007, PHARMACOTHERAPY, V27, P1313Tsujimura S, 2006, BIOSCI BIOTECH BIOCH, V70, P654D`Orazio P, 2006, CLIN CHEM LAB MED, V44, P1486, DOI 10.1515/CCLM.2006.275Nathan DM, 2005, NEW ENGL J MED, V353, P2643Wild S, 2004, DIABETES CARE, V27, P1047*CLIN LAB STAND I, 2004, EP5A2 CLSI*CLIN LAB STAND I, 2003, EP6A CLSI*INT ORG STAND, 2003, 151972003E ISO*CLIN LAB STAND I, 2002, EP7A CLISTang ZP, 2001, CRIT CARE MED, V29, P1062Tang ZP, 2000, AM J CLIN PATHOL, V113, P75Turner RC, 1998, LANCET, V352, P837*CLIN LAB STAND I, 1995, EP9A CLSI1994, DIABETES CARE, V17, P81MERENSTEIN GB, 1993, PEDIATRICS, V92, P4741993, N ENGL J MED, V329, P977BARRETT AE, 1979, J CLIN PATHOL, V32, P893

    Large scale and integrated platform for digital mass culture of anchorage dependent cells

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    Industrial applications of anchorage-dependent cells require large-scale cell culture with multifunctional monitoring of culture conditions and control of cell behaviour. Here, we introduce a large-scale, integrated, and smart cell-culture platform (LISCCP) that facilitates digital mass culture of anchorage-dependent cells. LISCCP is devised through large-scale integration of ultrathin sensors and stimulator arrays in multiple layers. LISCCP provides real-time, 3D, and multimodal monitoring and localized control of the cultured cells, which thereby allows minimizing operation labour and maximizing cell culture performance. Wireless integration of multiple LISCCPs across multiple incubators further amplifies the culture scale and enables digital monitoring and local control of numerous culture layers, making the large-scale culture more efficient. Thus, LISCCP can transform conventional labour-intensive and high-cost cell cultures into efficient digital mass cell cultures. This platform could be useful for industrial applications of cell cultures such as in vitro toxicity testing of drugs and cosmetics and clinical scale production of cells for cell therapy.
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