Cocoa polyphenols suppress TNF-α-induced vascular endothelial growth factor expression by inhibiting phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase kinase-1 (MEK1) activities in mouse epidermal cells

Cocoa polyphenols have antioxidant and anti-inflammatory effects. TNF-α is a pro-inflammatory cytokine that has a vital role in the pathogenesis of inflammatory diseases such as cancer and psoriasis. Vascular endothelial growth factor (VEGF) expression is associated with tumorigenesis, CVD, rheumatoid arthritis and psoriasis. We tested whether cocoa polyphenol extract (CPE) inhibited TNF-α-induced VEGF expression in promotion-sensitive JB6 mouse epidermal cells. CPE significantly inhibited TNF-α-induced up-regulation of VEGF via reducing TNF-α-induced activation of the nuclear transcription factors activator protein-1 (AP-1) and NF-κB, which are key regulators of VEGF expression. CPE also inhibited TNF-α-induced phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase. CPE blocked activation of their downstream kinases, p70 kDa ribosomal protein S6 kinase and p90 kDa ribosomal protein S6 kinase. CPE suppressed phosphoinositide 3-kinase (PI3K) activity via binding PI3K directly. CPE did not affect TNF-α-induced phosphorylation of mitogen-activated protein kinase kinase-1 (MEK1) but suppressed TNF-α-induced MEK1 activity. Collectively, these results indicate that CPE reduced TNF-α-induced up-regulation of VEGF by directly inhibiting PI3K and MEK1 activities, which may contribute to its chemopreventive potentia

CHF Enhancement of Advanced 37-Element Fuel Bundles

A standard 37-element fuel bundle (37S fuel bundle) has been used in commercial CANDU reactors for over 40 years as a reference fuel bundle. Most CHF of a 37S fuel bundle have occurred at the elements arranged in the inner pitch circle for high flows and at the elements arranged in the outer pitch circle for low flows. It should be noted that a 37S fuel bundle has a relatively small flow area and high flow resistance at the peripheral subchannels of its center element compared to the other subchannels. The configuration of a fuel bundle is one of the important factors affecting the local CHF occurrence. Considering the CHF characteristics of a 37S fuel bundle in terms of CHF enhancement, there can be two approaches to enlarge the flow areas of the peripheral subchannels of a center element in order to enhance CHF of a 37S fuel bundle. To increase the center subchannel areas, one approach is the reduction of the diameter of a center element, and the other is an increase of the inner pitch circle. The former can increase the total flow area of a fuel bundle and redistributes the power density of all fuel elements as well as the CHF. On the other hand, the latter can reduce the gap between the elements located in the middle and inner pitch circles owing to the increasing inner pitch circle. This can also affect the enthalpy redistribution of the fuel bundle and finally enhance CHF or dry-out power. In this study, the above two approaches, which are proposed to enlarge the flow areas of the center subchannels, were considered to investigate the impact of the flow area changes of the center subchannels on the CHF enhancement as well as the thermal characteristics by applying a subchannel analysis method

Negative regulation of ERα by a novel protein CAC1 through association with histone demethylase LSD1

AbstractERα, a critical transcriptional factor for breast cancer proliferation, is regulated by a complex binding repertoire that includes coactivators and corepressors. Here, we identified a novel class of ERα coregulator called CAC1. The CoRNR box of CAC1 was required for the binding to and inactivation of ERα. CAC1 also associated with histone demethylase LSD1 and suppressed LSD1-enhanced ERα activity. CAC1 impaired recruitment of ERα and LSD1 to the ERα-responsive promoter, leading to greater H3K9me3 accumulation. This effect was reversed by CAC1 depletion. Finally, CAC1 increased paclitaxel-induced cell death in ERα-positive MCF7 cells, which are paclitaxel-resistant. Overall, our study provides the first evidence that CAC1, associated with LSD1, functions as an ERα corepressor, implicating a potential antitumor target in ERα-positive breast cancer.Structured summary of protein interactionsER-alpha physically interacts with CAC1 by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3)LSD1 physically interacts with CAC1 by anti tag coimmunoprecipitation (View interaction)CAC1 binds to ER-alpha by pull down (View interaction)CAC1 and ER-alpha colocalizebyfluorescence microscopy (View interaction

Neural Substrate Responsible for Crossed Aphasia

Crossed aphasia (CA) refers to language impairment secondary to right hemisphere lesion. Imaging analysis on the lesion location of CA has not yet been reported in the literature. This study was proposed to analyze the most prevalent lesion site related to CA. Brain MRI of 7 stroke patients satisfying the criteria for CA were used to define Region of interest (ROIs) before overlaying the images to visualize the most overlapped area. Talairach coordinates for the most overlapped areas were converted to corresponding anatomical regions. Anatomical lesions where more than 3 patients' images were overlapped were considered significant. The overlayed ROIs of 7 patients revealed the lentiform nucleus as the most frequently involved area, overlapping in 6 patients. Our study first demonstrates the areas involved in CA by lesion mapping using brain MRI, and lentiform nucleus is the responsible neural substrate for crossed aphasia.Crossed aphasia (CA) refers to language impairment secondary to right hemisphere lesion. Imaging analysis on the lesion location of CA has not yet been reported in the literature. This study was proposed to analyze the most prevalent lesion site related to CA. Brain MRI of 7 stroke patients satisfying the criteria for CA were used to define Region of interest (ROIs) before overlaying the images to visualize the most overlapped area. Talairach coordinates for the most overlapped areas were converted to corresponding anatomical regions. Anatomical lesions where more than 3 patients' images were overlapped were considered significant. The overlayed ROIs of 7 patients revealed the lentiform nucleus as the most frequently involved area, overlapping in 6 patients. Our study first demonstrates the areas involved in CA by lesion mapping using brain MRI, and lentiform nucleus is the responsible neural substrate for crossed aphasia.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000005165/7SEQ:7PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000005165ADJUST_YN:YEMP_ID:A075663DEPT_CD:801CITE_RATE:1.249FILENAME:첨부된 내역이 없습니다.DEPT_NM:의학과EMAIL:[email protected]_YN:YCONFIRM:

Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration.

Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar-lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, damage-associated transient progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell differentiation. Importantly, chronic inflammation mediated by IL-1β prevents AT1 differentiation, leading to aberrant accumulation of DATPs and impaired alveolar regeneration. Together, this stepwise mapping to cell fate transitions shows how an inflammatory niche controls alveolar regeneration by controlling stem cell fate and behavior.We would like to thank Emma Rawlins (University of Cambridge, UK) for valuable scientific discussions and sharing the mouse lines; We would like to thank Randall Johnson (University of Cambridge, UK) for sharing Hif1aflox/flox mouse line; Nisha Narayan and Brian Huntly for sharing materials and discussion on glycolysis experiments; Irina Pshenichnaya (Histology), Maike Paramor (NGS library), Peter Humphreys (Imaging), Andy Riddell (Flow cytometry), Simon McCallum (Flow cytometry, Cambridge NIHR BRC Cell Phenotyping Hub), Katarzyna Kania (single cell sequencing at Cancer Research UK), and Cambridge Stem Cell Institute core facilities for technical assistance; Papworth Hospital Research Tissue Bank for providing tissue samples from IPF and lung adenocarcinoma (T02233); Kelly Evans for sharing histology samples of human lung tissue samples; Seungmin Han and Woochang Hwang for discussion on the scRNA-seq analysis; Life Science Editors for editorial assistance; All Lee Lab members for helpful discussion. This work was supported by Wellcome and the Royal Society (107633/Z/15/Z) and European Research Council Starting Grant (679411). J.C. was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A03005399)

Bloody nipple discharge in an infant

Although milky nipple discharge appears frequently in infants, bloody nipple discharge is a very rare finding. We experienced a 4-month-old, breast-fed infant who showed bilateral bloody nipple discharge with no signs of infection, engorgement, or hypertrophy. The infant's hormonal examination and coagulation tests were normal, and an ultrasound examination revealed mammary duct ectasia. The symptoms resolved spontaneously within 6 weeks without any specific treatment, except that we advised the mother to refrain from taking herbal medicine. Since no such case has been previously reported in Korea, we present this case with a brief review of the literature

Reducing Donor Site Morbidity When Reconstructing the Nipple Using a Composite Nipple Graft

BackgroundNumerous procedures are available for nipple reconstruction without a single gold standard. This study presents a method for reducing donor-site morbidity in nipple reconstruction using a composite nipple graft after transverse rectus abdominis musculocutaneous flap breast reconstruction.MethodsThirty-five patients who underwent nipple reconstruction using a composite nipple graft technique between July of 2001 and December of 2009 were enrolled in this study. To reduce the donor site morbidity, the superior or superior-medial half dome harvesting technique was applied preserving the lateral cutaneous branch of the fourth intercostal nerves. The patients were asked to complete a previously validated survey to rate the color and projection of both nipples, along with the sensation and contractility of the donor nipple; and whether, in retrospect, they would undergo the procedure again. To compare projection, we performed a retrospective chart review of all the identifiable patients who underwent nipple reconstruction using the modified top hat flap technique by the same surgeon and during the same period.ResultsThirty-five patients were identified who underwent nipple reconstruction using a composite nipple graft. Of those, 29 patients (82.9%) responded to the survey. Overall, we received favorable responses to the donor site morbidity. Projection at postoperative 6 months and 1 year was compared with the immediate postoperative results, as well as with the results of nipples reconstructed using the modified top hat flap.ConclusionsThe technique used to harvest donor tissue is important. Preserving innervation of the nipple while harvesting can reduce donor site morbidity