Functional elements demarcated by histone modifications in breast cancer cells

AbstractHistone modifications are regarded as one of markers to identify regulatory elements which are DNA segments modulating gene transcription. Aberrant changes of histone modification levels are frequently observed in cancer. We have employed ChIP-Seq to identify regulatory elements in human breast cancer cell line, MCF-7 by comparing histone modification patterns of H3K4me1, H3K4me3, and H3K9/14ac to those in normal mammary epithelial cell line, MCF-10A. The genome-wide analysis shows that H3K4me3 and H3K9/14ac are highly enriched at promoter regions and H3K4me1 has a relatively broad distribution over proximity of TSSs as well as other genomic regions. We identified that many differentially expressed genes in MCF-7 have divergent histone modification patterns. To understand the functional roles of distinctively histone-modified regions, we selected 35 genomic regions marked by at least one histone modification and located from 3 to 10kb upstream of TSS in both MCF-7 and MCF-10A and assessed their transcriptional activities. About 66% and 60% of selected regions in MCF-7 and MCF-10A, respectively, enhanced the transcriptional activity. Interestingly, most regions marked by H3K4me1 exhibited an enhancer activity. Regions with two or more kinds of histone modifications did show varying activities. In conclusion, our data reflects that comprehensive analysis of histone modification profiles under cell type-specific chromatin environment should provide a better chance for defining functional regulatory elements in the genome

Treatment response with potassium-competitive acid blockers based on clinical phenotypes of gastroesophageal reflux disease: A systematic literature review and meta-analysis

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. METHODS: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. RESULTS: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. CONCLUSIONS: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn

Comparison of anterior segment optical coherence tomography findings in acanthamoeba keratitis and herpetic epithelial keratitis

This study is to investigate the characteristic features of Acanthamoeba keratitis (AK) that differentiating it from herpetic epithelial keratitis (HEK) using anterior segment optical coherence tomography (AS-OCT). Medical records of three eyes of each AK and herpetic keratitis who had AS-OCT examination were reviewed in this study. Slit-lamp biomicroscopy and AS-OCT was performed on the initial visit and on every follow-up visits in all patients. In all three AK cases, reflective bands in the corneal stroma that correspond to the area of radial keratoneuritis were observed. The depth of the reflective bands varied in each case. After AK treatment, slit-lamp biomicroscopy confirmed that radial keratoneuritis had resolved and AS-OCT confirmed that reflective bands in the corneal stroma had also disappeared in all patients. Unlike the AS-OCT results found in AK, highly reflective HEK lesions were observed only in the subepithelial area, not in the stroma. AS-OCT seems to be helpful analyzing the specific depth of the lesion which enables to distinguish AK from HEK

Bilateral Endophthalmitis as the Initial Presentation of Bacterial Meningitis

To report a case of bilateral endophthalmitis as the initial presentation of bacterial meningitis in a young, immunocompetent Korean patient. A 35-year-old female with a one day history of bilateral swollen eyes, visual disturbance, headache, petechial skin rash, and nausea visited our clinic. She was diagnosed as having endogenous endophthalmitis associated with bacterial meningitis. Intravenous broad spectrum antibiotic therapy was initiated with cefotaxime 3 g and ubacillin 3 g, four times daily. Intravitreal antibiotic (vancomycin 1 mg/0.1 mL and ceftazidime 2 mg/0.1 mL) injections were performed in both eyes. Two weeks post presentation, the best corrected visual acuity in both eyes improved to 0.7, and inflammation of the anterior chamber and vitreous cavity was decreased. We recommend that when endogenous endophthalmitis is suspected along with meningitis, or if it is known to be present, intravitreal and intravenous antibiotics should be promptly administered to preserve vision

Spontaneous Anterior Lens Capsular Dehiscence Causing Lens Particle Glaucoma

To report acute onset lens particle glaucoma associated with a spontaneous anterior capsular dehiscence. A 66-year-old man presented with spontaneous anterior lens capsule dehiscence with an acute onset of right eye pain that was associated with white particles in the anterior chamber angle and intraocular pressure (IOP) of 55 mmHg. No trauma or other inflammatory antecedents were reported. A hypermature cataract was observed at slit lamp exam. After medical treatment without IOP control, we performed extracapsular cataract extraction and anterior vitrectomy. Anterior chamber aspirate confirmed the presence of macrophages. The postoperative IOP at one month was 16 mmHg OD without medication. Spontaneous dehiscence of the anterior lens capsule in a patient with a hypermature cataract may release lens cortical material, resulting in lens particle glaucoma. Prompt surgical removal of the lens material usually controls the high IOP, and the need for additional glaucoma surgery is not common

Beneficial Effects of Traditional Seasonings on Quality Characteristics of Fermented Sausages

Though traditional seasonings are widely used in many dishes, however, no attention has been paid to the investigation of their effects on quality characteristics of food products. The present investigation was undertaken to study the effects of incorporating several traditional seasonings including doenjang (fermented soybean paste), gochu-jang (red pepper paste), fresh medium-hot, and hot peppers, and fresh garlic on the lipid oxidation, cholesterol content and sensory characteristics of fermented sausages. Six fermented sausage treatments (5 with 1% (w/w) each test seasoning and 1 without added test seasoning (control) were prepared. The addition of seasonings generally had beneficial effects on the improvement of fermented sausage’s quality however the effects differed depending on the each type of seasonings added. Significant lower pH values were found in all fermented sausages made with the seasonings while, lower levels of lipid oxidation were found in the treatments with hot peppers and garlic as compared with the control (p<0.05). The treatment with seasonings did not cause color or texture defects in the products whereas the sausages made with gochu-jang had significantly higher Commission International de l’Eclairagea* (redness) value in comparison with the control. Noticeably, incorporating doenjang, medium-hot peppers, hot peppers and garlic resulted in reduction of 26.50, 32.54, 47.04, and 48.54 mg cholesterol/100 g samples, respectively (p<0.05). Higher scores for the sensory traits such as aroma, taste, color and acceptability were also given for the sausages made with seasonings. The current work demonstrates that the test seasonings represent potentially natural ingredients to be used for producing healthier fermented sausages

Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway

Atopic Dermatitis-Like Skin Lesions Reduced by Topical Application and Intraperitoneal Injection of Hirsutenone in NC/Nga Mice

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD

Imaging Findings of Castleman's Disease Localized in the Axilla: A Case Report

Castleman's disease is a rare benign lymphoproliferative disorder of uncertain origin which most commonly involves the mediastinum but rarely affects the axilla. We report a case of localized Castleman's disease involving the axillary lymph node. Mammography revealed a well-defined, homogeneously dense ovoid mass, 3 cm in size, in the left axilla, while gray-scale ultrasonography (US) demonstrated a well-defined, uniformly hypoechoic ovoid mass with good through transmission. Peripheral hypervascularity was observed at power Dopper US, and early rapid homogeneous enhancement at contrast-enhanced dynamic CT

Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice

Myung Joo Kang1,&amp;nbsp;Jae Yoon Eum1, Mi Sook Jeong2, Sang Han Park1, Ki Young Moon1, Mean Hyung Kang1, Min Soo Kim1, Sun Eun Choi1, Min Won Lee1, Do Ik Lee1, Hyoweon Bang2, Chung Soo Lee2, Seong Soo Joo3, Kapsok Li2, Mi-Kyung Lee2, Seong Jun Seo2, Young Wook Choi11College of Pharmacy, ChungAng University, Heuksuk-dong, Dongjak-gu, Seoul, 2College of Medicine, Chung-Ang University, Heuksukdong, Dongjak-gu, Seoul, 3Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, South KoreaBackground: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).Methods: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed.Results: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils.Conclusion: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.Keywords: hirsutenone, elastic liposomes, atopic dermatitis, NC/Nga mice, Tat peptid