Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway

The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 µg/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 µg/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-α and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-α or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Preventative Effects of Antioxidants against PM10 on Serum IgE Concentration, Mast Cell Counts, Inflammatory Cytokines, and Keratinocyte Differentiation Markers in DNCB-Induced Atopic Dermatitis Mouse Model

Particulate matter (PM) can cause oxidative stress, inflammation, and skin aging. We investigated the effects of antioxidants such as dieckol, punicalagin, epigallocatechin gallate (EGCG), resveratrol, and Siegesbeckiae Herba extract (SHE) against PM &lt; 10 &mu;m (PM10) on serum IgE concentration, mast cell counts, inflammatory cytokines, and keratinocyte differentiation markers in a 2,4-Dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. Seven-week-old BALB/c mice were sensitized with 2% DNCB. Atopic dermatitis-like lesions were induced on the mice with 0.2% DNCB. Antioxidants and PM10 were applied to the mice for 4 weeks. PM10 increased the serum IgE concentration and spleen weight in mice, and all antioxidants downregulated these parameters. Histological examination showed an increase in epidermal thickness and mast cell counts in response to PM10, and all antioxidants showed a decrease. PM10 upregulates the expression of inflammatory cytokines, including interleukin (IL)-1&beta;, IL-4, IL-6, IL-17&alpha;, IL-25, IL-31 and thymic stromal lymphopoietin (TSLP) in mice, and all antioxidants inhibited the upregulation of inflammatory cytokines. ELISA showed the same results as real-time PCR. PM10 downregulates the expression of keratinocyte differentiation markers, including loricrin and filaggrin, in mouse keratinocytes and antioxidants prevented the downregulation of the keratinocyte differentiation markers. Conclusively, PM10 aggravated the DNCB-induced mouse model in serum IgE concentration, mast cell counts, inflammatory cytokine, and keratinocyte differentiation markers. In addition, antioxidants modulated changes in the DNCB-induced mouse model caused by PM10

The Pre-Heating Effect for Porosity Control during the Laser Welding of Galvanized Steel Sheets

Recently, for the high performance of automobiles, the application ratio of zinc-coated steel sheets with excellent corrosion resistance has been increasing. However, it is difficult to achieve sound welds, as porosities form from zinc during welding. In this study, a laser welding process, with the addition of a pretreatment step to conventional laser welding, was devised to improve weld quality by eliminating pores caused by zinc in the welds. Laser welding was performed on the overlapping joint of hot-dip galvanized steel sheets (SGARC 340, Hyundai Steel., Suncheon-Si, Jeollanam-do, Republic of Korea), with a thickness of 1.2 mm in the upper sheet and 0.9 mm in the lower sheet, and the welding characteristics were investigated by varying the laser power and focal position. Compared to conventional laser welding, the three-step laser stitch welding process significantly reduced the degree of spatter generation and welding defects. Additionally, it increased the tensile–shear load by approximately 37%. Moreover, the reduction in the zinc component of the three-step laser stitch welds was confirmed through SEM-EDS analysis. These findings contribute valuable information for securing high-quality welding joints and effectively addressing zinc-coated steel sheet welding quality issues in the automotive and industrial sectors

Integrated monitoring of the ATLAS online computing farm

The online farm of the ATLAS experiment at the LHC, consisting of nearly 4000 PCs with various characteristics, provides configuration and control of the detector and performs the collection, processing, selection and conveyance of event data from the front-end electronics to mass storage. The status and health of every host must be constantly monitored to ensure the correct and reliable operation of the whole online system. This is the first line of defense, which should not only promptly provide alerts in case of failure but, whenever possible, warn of impending issues. The monitoring system should be able to check up to 100000 health parameters and provide alerts on a selected subset. In this paper we present the implementation and validation of our new monitoring and alerting system based on Icinga 2 and Ganglia. We describe how the load distribution and high availability features of Icinga 2 allowed us to have a centralised but scalable system, with a configuration model that allows full flexibility while still guaranteeing complete farm coverage. Finally, we cover the integration of Icinga 2 with Ganglia and other data sources, such as SNMP for system information and IPMI for hardware health

Comparison of pancreatic lipase inhibitory isoflavonoids from unripe and ripe fruits of <i>Cudrania tricuspidata</i>

<div><p>The composition and content of the active constituents and their biological activity vary according to diverse factors including their maturation stages. A previous study showed that the fruits of <i>Cudrania tricuspidata</i> inhibited pancreatic lipase activity, a key enzyme in fat absorption. In this study, we investigated the chemical composition and pancreatic lipase inhibitory activity of unripe and ripe fruits of <i>C</i>. <i>tricuspidata</i>. Unripe fruits of <i>C</i>. <i>tricuspidata</i> have a higher content of total phenolic and flavonoids and exhibited stronger pancreatic lipase inhibition compared to ripe fruits. HPLC analysis revealed the different chemical compositions of the unripe and ripe fruits. Further fractionation resulted in the isolation of 30 compounds including two new isoflavonoids. Analysis of the chemical constituents of the unripe and ripe fruits revealed that a 2,2-dimethylpyran ring, a cyclized prenyl, was the predominant side chain in the unripe fruits, whereas it was a linear prenyl group in the ripe fruits. In addition, a new isoflavonoid (<b>19</b>) from the unripe fruits showed the most potent inhibition on pancreatic lipase. Taken together, the maturation stage is an important factor for maximum efficacy and that unripe fruits of <i>C</i>. <i>tricuspidata</i> are a good source of new bioactive constituents for the regulation of obesity</p></div