Sulforaphane prevents doxorubicin-induced oxidative stress and cell death in rat H9c2 cells

LI, BO,KIM, DO SUNG,YADAV, RAJ KUMAR,KIM, HYUNG RYONG,CHAE, HAN JUNG UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.36 No.1

<P>Sulforaphane, a natural isothiocyanate compound found in cruciferous vegetables, has been shown to exert cardioprotective effects during ischemic heart injury. However, the effects of sulforaphane on cardiotoxicity induced by doxorubicin are unknown. Thus, in the present study, H9c2 rat myoblasts were pre-treated with sulforaphane and its effects on cardiotoxicity were then examined. The results revealed that the pre-treatment of H9c2 rat myoblasts with sulforaphane decreased the apoptotic cell number (as shown by trypan blue exclusion assay) and the expression of pro-apoptotic proteins (Bax, caspase-3 and cytochrome <I>c</I>; as shown by western blot analysis and immunostaining), as well as the doxorubicin-induced increase in mitochondrial membrane potential (measured by JC-1 assay). Furthermore, sulforaphane increased the mRNA and protein expression of heme oxygenase-1 (HO-1, measured by RT-qPCR), which consequently reduced the levels of reactive oxygen species (ROS, measured using MitoSOX Red reagent) in the mitochondria which were induced by doxorubicin. The cardioprotective effects of sulforaphane were found to be mediated by the activation of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor-2 (Nrf2)/antioxidant-responsive element (ARE) pathway, which in turn mediates the induction of HO-1. Taken together, the findings of this study demonstrate that sulforaphane prevents doxorubicin-induced oxidative stress and cell death in H9c2 cells through the induction of HO-1 expression.</P>

Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL-2H3 cells

YOO, JAE-MYUNG,YANG, JU HYE,YANG, HYE JIN,CHO, WON-KYUNG,MA, JIN YEUL UNKNOWN 2016 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.37 No.2

<P>Arctium lappa fruit has been used in traditional medicine, and it is known to exert beneficial effects, such as antioxidant, anti-inflammatory and anticancer effects. However, the effects of the Arctium lappa fruit on the allergic response remain unknown. In this study, we evaluated the anti-allergic effects of Arctium lappa fruit extract (AFE) and its fermented form (F-AFE) using immunoglobulin E (IgE)-activated RBL-2H3 cells. To investigate the anti-allergic effects of AFE or F-AFE, we examined the release of beta-hexosaminidase, a key biomarker of degranulation during an allergic reaction, and the production of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E-2 (PGE(2)) in the cells treated with or without the above-mentioned extracts. AFE weakly inhibited the release of beta-hexosaminidase, whereas F-AFE significantly suppressed the release of beta-hexosaminidase in a dose-dependent manner. Consistently, F-AFE suppressed the production of TNF-a and PGE2 in a dose-dependent manner. F-AFE exerted an inhibitory effect on the production of beta-hexosaminidase, TNF-a and PGE2 with an IC50 value of 30.73, 46.96 and 36.27 mu g/ml, respectively. Furthermore, F-AFE inhibited the phosphorylation of Lyn, Fyn and Syk, which are involved in the FceRI signaling pathway, that of phosphoinositide phospholipase C (PLC)gamma 1/2 and protein kinase C (PKC)delta, which are associated with the degranulation process, as well as that of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK), p38 and Akt, which are associated with cytokine expression. In the late phase, F-AFE partially suppressed the phosphorylation of cytosolic phospholipase A(2) (cPLA(2)), but not the expression of cyclooxygenase (COX)-2. To compare and identify the major components of the two extracts, we used high-performance liquid chromatography. The levels of arctigenin, one of the major compounds, were elevated 6-fold in F-AFE compared with AFE, whereas the levels of arctiin, an arctigenin glycoside, were decreased in F-AFE by approximately 57.40%. These results suggest that arctigenin plays an important role in the anti-allergic effects of F-AFE. Taken together, F-AFE containing anti-allergic phytochemicals, including arctigenin, inhibited the activation of the FceRI receptor induced by the antigen-IgE complex. Such effects may provide further information for the development of a phytomedicine for allergic diseases.</P>

Systemic Inflammation Is Associated With Coronary Artery Calcification and All-Cause Mortality in Chronic Kidney Disease

Hwang, In-Chang,Park, Hyo Eun,Kim, Hack-Lyoung,Kim, Hyue Mee,Park, Jun-Bean,Yoon, Yeonyee E.,Lee, Seung-Pyo,Kim, Hyung-Kwan,Cho, Goo-Yeong,Sohn, Dae-Won UNKNOWN 2016 CIRCULATION JOURNAL Vol.80 No.7

<P>Background: Presence of systemic inflammation in chronic kidney disease (CKD) is associated with advanced coronary artery calcification (CAC). The prognostic significance of this association, however, is unknown. We evaluated the associations between CAC, estimated glomerular filtration rate (eGFR) and all-cause mortality, to determine whether the associations differ according to the presence of systemic inflammation. Methods and Results: We followed 30,703 consecutive individuals who underwent CAC measurement for a median of 79 months (IQR, 65-96 months). Patients were categorized according to baseline CAC score (0, 1-99, 100-399 and >= 400), eGFR (<45, 45-59, 60-74, 75-89, 90-104, and >= 105 ml/min/1.73 m(2)) and high-sensitivity C-reactive protein (hsCRP; <2.0, and >= 2.0 mg/L). Prevalence and extent of CAC were greater in those with lower eGFR and higher hsCRP accordingly, even after adjustment. Lower eGFR was strongly associated with higher CAC score (>= 400), and the association was more significant in patients with higher hsCRP. The greater CAC burden was associated with worse outcome in the CKD patients (eGFR <60 ml/min/1.73 m(2)) only in those with higher hsCRP. Conclusions: Patients with low eGFR and more extensive CAC had greater risk of mortality, and associations differed according to the presence of systemic inflammation. Among the CKD patients, coronary evaluation may be considered for those with elevated hsCRP.</P>

Multimodality Imaging in Patients with Secondary Hypertension: With a Focus on Appropriate Imaging Approaches Depending on the Etiologies

Ahn, Hyungwoo,Chun, Eun Ju,Lee, Hak Jong,Hwang, Sung Il,Choi, Dong-Ju,Chae, In-Ho,Lee, Kyung Won unknown 2018 KOREAN JOURNAL OF RADIOLOGY Vol.19 No.2

<P>Although the causes of hypertension are usually unknown, about 10% of the cases occur secondary to specific etiologies, which are often treatable. Common categories of secondary hypertension include renal parenchymal disease, renovascular stenosis, vascular and endocrinologic disorders. For diseases involving the renal parenchyma and adrenal glands, ultrasonography (US), computed tomography (CT) or magnetic resonance (MR) imaging is recommended. For renovascular stenosis and vascular disorders, Doppler US, conventional or noninvasive (CT or MR) angiography is an appropriate modality. Nuclear imaging can be useful in the differential diagnosis of endocrine causes. Radiologists should understand the role of each imaging modality and its typical findings in various causes of secondary hypertension. This article focuses on appropriate imaging approaches in accordance with the categorized etiologies leading to hypertension.</P>

Gene amplifications at chromosome 7 of the human gastric cancer genome

UNKNOWN 2007 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.20 No.2

Novel mutations in the human elastin gene (ELN) causing isolated supravalvular aortic stenosis.

Park, Seonmin,Seo, Eul-Ju,Yoo, Han-Wook,Kim, Youngho UNKNOWN 2006 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.18 No.2

<P>Supravalvular aortic stenosis (SVAS), an inherited vascular disease, is caused by mutations in the elastin gene (ELN). Our aim was to identify novel mutations of ELN and to determine the expression of ELN in patients with SVAS. For screening mutations in ELN, we performed PCR-directed sequence analysis with genomic DNA isolated from SVAS patients and control subjects. Expression of ELN at the mRNA and protein levels were assessed by real-time PCR and Western blot analyses, respectively, using primary skin fibroblast cultures established from SVAS patients and control subjects. We identified two novel mutations of ELN, G297_A308del and Q700X, in two unrelated Korean patients with isolated SVAS. G297_A308del occurred de novo while Q700X was derived maternally. In the patient with G297_A308, elastin expression was not significantly altered at the mRNA level, but was reduced to approximately 50% of the normal control at the protein level. The elastin expression levels in the patient with Q700X were reduced to <50% of the normal controls at both the mRNA and protein levels. Our findings confirm that functional haploinsufficiency of elastin is responsible for the pathogenesis associated with isolated SVAS across different ethnic backgrounds.</P>

Comparison of waveform inversion, part 3: amplitude approach

Pyun, Sukjoon,Shin, Changsoo,Bednar, J. B. unknown 2007 Geophysical prospecting Vol.55 No.4

<P>ABSTRACT</P><P>In the second paper of this three part series, we studied the case of conventional and logarithmic phase-only approaches to full-waveform inversion. Here, we concentrate on deriving amplitude-only approaches for both conventional- and logarithmic-based methods. We define two amplitude-only objective functions by simply assuming that the phase of the modelled wavefield is equal to that of the observed wavefield. We do this for both the conventional least-squares approach and the logarithmic approach of Shin and Min. We show that these functions can be optimized using the same reverse-time propagation algorithm of the full conventional methodology. Although the residuals in this case are not really residual wavefields, they can both be considered and utilized in that sense. In contrast to the case for our phase-only algorithms, we show through numerical tests that the conventional amplitude-only inversion is better than the logarithmic method.</P>

A new homogeneity index based on statistical analysis of the dose–volume histogram

Yoon, Myonggeun,Park, Sung Yong,Shin, Dongho,Lee, Se Byeong,Pyo, Hong Ryull,Kim, Dae Yong,Cho, Kwan Ho unknown 2007 Journal of applied clinical medical physics Vol.8 No.2

<P>The goal of the present study was to develop a new dose–volume histogram (DVH)– based homogeneity index for effectively evaluating the dose homogeneity of intensity‐modulated radiotherapy plans. The new index, called the sigma‐index (“<I>S</I>‐index”) is defined as the standard deviation of the normalized differential DVH curve. In a study of 16 patients with brain tumors at our institution, the <I>S</I>‐index was found to vary from 0.80 to 3.15. Our results showed that the <I>S</I>‐index provides a more reliable and accurate measure of dose homogeneity than that given by conventional methods. A guideline for evaluating the dose homogeneity of treatment plans based on the <I>S</I>‐index and its relation to equivalent uniform dose is discussed.</P><P>PACS numbers: 87.53.Xd, 87.53.Tf</P>

Toll-like receptor family members in skin fibroblasts are functional and have a higher expression compared to skin keratinocytes

YAO, CHENG,OH, JANG-HEE,LEE, DONG HUN,BAE, JUNG-SOO,JIN, CHENG LONG,PARK, CHI-HYUN,CHUNG, JIN HO UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.35 No.5

<P>Toll-like receptors (TLRs) are known to recognize not only pathogen-associated molecular patterns but also danger-associated molecular patterns. Recent studies have characterized the expression levels and functions of TLRs in human epidermal cells. However, the characteristics of TLR family members in human dermal fibroblasts have not been thoroughly studied. Therefore, the present study systematically investigated the expression levels of TLRs and their functional responses to each ligand in skin fibroblasts. All 10 TLRs are expressed in skin fibroblasts. Stimulation of skin fibroblasts with each TLR ligand resulted in an increase of the interleukin-6 (IL-6), IL-8 and matrix metalloproteinase-1 proteins, indicating that 9 TLRs in skin fibroblasts are functionally active. Furthermore, stimulating skin fibroblasts with TLR1/2, 3 and 4 ligands induced the phosphorylation of inhibitor of nuclear factor κBα and the active phosphorylation of extracellular-signal regulated kinase 1/2. The expression level of each TLR was much higher in fibroblasts compared to keratinocytes. In particular, the fold-increase in IL-6 and IL-8 mRNA levels upon exposure to a TLR1/2 ligand was much higher in fibroblasts compared to keratinocytes, which appears to reflect the difference in expression levels of TLR1 and 2 between fibroblasts and keratinocytes. Taken together, these results show that all 10 TLRs are constitutively expressed and functional (except TLR10) in skin fibroblasts and suggest that TLRs in skin fibroblasts may play an important role in the detection of and response to different classes of pathogens and danger signals.</P>

Evaluation of estrogenic activity and measurement of EDCs in wastewater treatment plants

Lee, B. C.,Jung, J. Y.,Kim, H. K. unknown 2006 JOURNAL- OCEAN UNIVERSITY OF CHINA Vol.5 No.4