<div>Abstract<p>Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-κB (NF-κB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 μmol/L, EGCG abrogates p300-induced p65 acetylation <i>in vitro</i> and <i>in vivo</i>, increases the level of cytosolic IκBα, and suppresses tumor necrosis factor α (TNFα)–induced NF-κB activation. We also showed that EGCG prevents TNFα-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-κB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-κB target genes in response to diverse stimuli. Finally, EGCG reduced the binding of p300 to the promoter region of <i>interleukin-6</i> gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-κB–mediated inflammatory signaling pathway. Importantly, EGCG at 50 μmol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases. [Cancer Res 2009;69(2):583–92]</p></div>
<div>Abstract<p>Although multiple studies have revealed that gallic acid plays an important role in the inhibition of malignant transformation, cancer development, and inflammation, the molecular mechanism of gallic acid in inflammatory diseases is still unclear. In this study, we identified gallic acid from <i>Rosa rugosa</i> as a histone acetyltransferase (HAT) inhibitor with global specificity for the majority of HAT enzymes, but with no activity toward epigenetic enzymes including sirtuin (silent mating type information regulation 2 homologue) 1 (<i>S. cerevisiae</i>), histone deacetylase, and histone methyltransferase. Enzyme kinetic studies indicated that gallic acid uncompetitively inhibits p300/CBP-dependent HAT activities. We found that gallic acid inhibits p300-induced p65 acetylation, both <i>in vitro</i> and <i>in vivo</i>, increases the level of cytosolic IκBα, prevents lipopolysaccharide (LPS)-induced p65 translocation to the nucleus, and suppresses LPS-induced nuclear factor-κB activation in A549 lung cancer cells. We have also shown that gallic acid treatment inhibits the acetylation of p65 and the LPS-induced serum levels of interleukin-6 <i>in vivo</i>. Importantly, gallic acid generally inhibited inflammatory responses caused by other stimuli, including LPS, IFN-γ, and interleukin-1β, and further downregulated the expression of nuclear factor-κB–regulated antiapoptotic genes. These results show the crucial role of acetylation in the development of inflammatory diseases. (Mol Cancer Res 2009;7(12):2011–21)</p></div>
Background and Objectives：The purpose of this study is to compare the new Core ® stent and PalmazSchatz ® (PS stent in a porcine coronary stent restenosis model. Methods：Twelve pigs underwent balloon injury followed by implantation of oversized, tubular-type Core ® and PS ® stents (stent/artery ratio 1.2：1 in twenty-four coronary arteries. Quantitative analyses of the initial and follow-up coronary angiograms at 4 weeks after stenting was performed. The extents of injury and the neointimal area were compared between the two stented groups according to morphometric analysis. The stent flexibility and longitudinal staightening effect were compared between the two groups by the bending test and measurement of the angle changes. Results：1 The reference vessel diameter, stented artery diameter, and diameter of the stenosis were not different between the two groups. 2 The neointimal area was significantly smaller in the Core ® stent group than in the PS ® stent group (1.81±0.67 mm 2 vs 2.93±0.94 mm 2 , p＝0.006. 3 The Core ® stent had more flexible property than the PS ® stent. 4 The angle changes following stent implantation did not differ between the two groups(13.2±9.0, 14.4±11.1, p＝0.88. Conclusion：Core ® stent is effective in the inhibition of neointimal formation in a porcine coronary stent restenosis model. These results may be due to the improved flexibility of the Core ® stent, although further clinical trials may be needed. (Korean Circulation J 2001; 31(7 :655-661
<div>Abstract<p>Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-κB (NF-κB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 μmol/L, EGCG abrogates p300-induced p65 acetylation <i>in vitro</i> and <i>in vivo</i>, increases the level of cytosolic IκBα, and suppresses tumor necrosis factor α (TNFα)–induced NF-κB activation. We also showed that EGCG prevents TNFα-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-κB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-κB target genes in response to diverse stimuli. Finally, EGCG reduced the binding of p300 to the promoter region of <i>interleukin-6</i> gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-κB–mediated inflammatory signaling pathway. Importantly, EGCG at 50 μmol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases. [Cancer Res 2009;69(2):583–92]</p></div>
Acute respiratory distress syndrome (ARDS) has been reported to be associated with a variety of medical and surgical conditions, including All-trans-retinoic acid (ATTA). ATRA is very efficaceous drug to acute promyelocytic leukemia (APL). This drug can induce complete remission at APL without fatal risk of disseminated intravascular coagulation. But ATRA treatment, sometimes, produces the symptoms of fever, weight gain and acute respiratory distress, renal function impairment. The causes of these symptoms are not fully proved, but supposed as the result of leukostasis and capillary leak syndrome from excessive leukocyte differentiation and cytokines release. Recently, we experienced a 24-year-old woman who complained gum bleeding for 6 days. At bone marrow biopsy, she was diagnosed as APL. 2 days after ATRA treatment, she was suffered from the symptoms of dyspnea and general ache. At laboratory examination, total leukocyte count was 50,400/mm3 PaO2 was 42.5 mmHg and chest PA revealed the findings compatible with ARDS.Treatment with low dose ara-C, corticosteroid and general supportive cares were tried. Within 3 days after treatment, the patient recovered from ADRD by evidence of arterial blood gas study and chest radiographs. She has acquired complete remission of APL with maintenance of ATRA. And so, we present this case with a review of related literatures.
Background : The combined use of small endoscopic sphincterotomy (EST) followed by endoscopic papillary large balloon dilation (EPLBD) might be associated with a lower incidence of procedure-related complications such as pancreatitis, bleeding or perforation, compared to the use of EPLBD or a large EST alone. The aim of this retrospective study was to evaluate the utility of a combined EST and EPLBD method for the removal of common bile duct (CBD) stones that could not be extracted by use of an EST and conventional techniques. Methods : Between March 2005 and September 2006, a total of 35 patients with CBD stones were enrolled. Fourteen patients had received a previous EST, and 21 patients underwent an EST. The sphincterotomy site was then dilated with a 12~18 mm diameter balloon. Results : The average number of stones was 3.6±2.9 (range: 110). The average maximum stone diameter was 26.11 ±8.88 mm (range: 12~50 mm). Complete stone removal was accomplished in 31 patients (88.6%). In 9 patients (25.7%), a mechanical lithotripsy was required. No episode of true pancreatitis occurred. A procedure-related perforation occurred in one patient (2.8%) and the patient was treated with NPO and antibiotics. No procedure-related bleeding or mortality was observed. The procedure was performed safely in 9 patients (25.7%) with a periampullary diverticulum and in 14 patients (40.0%) with a previous EST. Conclusions : Combined EST and EPLBD may be a safe and effective method, and may be a good alternative treatment for removing CBD stones that cannot be extracted by an EST and conventional techniques. However, prospective studies based on a large number of patients are needed.
Abstract Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-κB (NF-κB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 μmol/L, EGCG abrogates p300-induced p65 acetylation in vitro and in vivo, increases the level of cytosolic IκBα, and suppresses tumor necrosis factor α (TNFα)–induced NF-κB activation. We also showed that EGCG prevents TNFα-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-κB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-κB target genes in response to diverse stimuli. Finally, EGCG reduced the binding of p300 to the promoter region of interleukin-6 gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-κB–mediated inflammatory signaling pathway. Importantly, EGCG at 50 μmol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases. [Cancer Res 2009;69(2):583–92]
Supplementary Figure 1 from Epigallocatechin-3-Gallate, a Histone Acetyltransferase Inhibitor, Inhibits EBV-Induced B Lymphocyte Transformation via Suppression of RelA Acetylation
Supplementary Table 1 from Epigallocatechin-3-Gallate, a Histone Acetyltransferase Inhibitor, Inhibits EBV-Induced B Lymphocyte Transformation via Suppression of RelA Acetylation
Supplementary Figure 2 from Epigallocatechin-3-Gallate, a Histone Acetyltransferase Inhibitor, Inhibits EBV-Induced B Lymphocyte Transformation via Suppression of RelA Acetylation
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