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https://www.readbyqxmd.com/read/29667067/a-first-in-class-inhibitor-mln4924-pevonedistat-induces-cell-cycle-arrest-senescence-and-apoptosis-in-human-renal-cell-carcinoma-by-suppressing-ube2m-dependent-neddylation-modification
#1
Bo Xu, Yuyou Deng, Ran Bi, Haoran Guo, Chang Shu, Neelam Kumari Shah, Junliang Chang, Guanchen Liu, Yujun Du, Wei Wei, Chunxi Wang
PURPOSE: MLN4924 is a second-generation inhibitor that targets ubiquitin-proteasome system by inhibiting neddylation activation enzyme (NAE), and subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs), which leads to the accumulation of CRLs substrates and hence, suppressing diverse tumor development. In this study, we investigated the potential application of this first-in-class inhibitor MLN4924 in the treatment of human renal cell carcinoma both in vitro and in vivo...
April 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29649793/long-term-effects-of-middle-ear-tendon-resection-on-middle-ear-myoclonic-tinnitus-hearing-and-hyperacusis
#2
Dong-Kee Kim, Jung Mee Park, Jung Ju Han, Yun Min Chung, Jung Min Kim, So Young Park, Shi Nae Park
OBJECTIVE: To evaluate the therapeutic effects of middle ear tendon resection (METR) on middle ear myoclonic tinnitus (MEMT) and to investigate its long-term effects on hearing and hyperacusis. MATERIALS AND METHODS: Thirty-seven patients with MEMT with a mean age of 33.2 ± 11.8 years were included in this study. METR was performed on all 37 MEMT patients (41 ears) between November 2004 and August 2016. The mean follow-up period was 16.1 months. We examined changes in tinnitus and accompanying stress and depression in patients after surgery, and examined the hearing changes and the occurrence of complications including hyperacusis...
April 12, 2018: Audiology & Neuro-otology
https://www.readbyqxmd.com/read/29587475/microbiological-results-from-middle-ear-effusion-in-pediatric-patients-receiving-ventilation-tube-insertion-multicenter-registry-study-on-the-effectiveness-of-ventilation-tube-insertion-in-pediatric-patients-with-chronic-otitis-media-with-effusion-part-i
#3
Myung Hoon Yoo, Yang-Sun Cho, June Choi, Yun Hoon Choung, Jae-Ho Chung, Jong Woo Chung, Gyu Cheol Han, Eun-Ju Jeon, Beom Cho Jun, Dong-Kee Kim, Kyu Sung Kim, Jun Ho Lee, Kyu-Yup Lee, Seung Hwan Lee, In Seok Moon, Hong Ju Park, Shi Nae Park, Jihye Rhee, Jae Hyun Seo, Seung Geun Yeo
Objectives: The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion. Methods: Patients <15 years old who were diagnosed as having OME and received ventilation tube insertion were prospectively enrolled in 16 tertiary hospitals from June 2014 to December 2016...
March 28, 2018: Clinical and Experimental Otorhinolaryngology
https://www.readbyqxmd.com/read/29567427/n-acylethanolamine-hydrolyzing-acid-amidase-inhibition-tools-and-potential-therapeutic-opportunities
#4
REVIEW
Pauline Bottemanne, Giulio G Muccioli, Mireille Alhouayek
The development of potent and selective NAAA inhibitors enables the control of NAE levels in several pathophysiological settings. NAAA inhibitors could be considered as anti-inflammatory and analgesic agents.
March 19, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29553518/synthesis-and-mass-spectrometry-analysis-of-oligo-peptoids
#5
Jianhua Ren, Yadwinder S Mann, Yuntao Zhang, Michael D Browne
Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques...
February 21, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29543636/low-level-viremia-is-associated-with-clinical-progression-in-hiv-infected-patients-receiving-antiretroviral-treatment
#6
Enrique Bernal, Jose Miguel Gómez, Inma Jarrín, Alfredo Cano, Angeles Muñoz, Antonia Alcaraz, Arkaitz Imaz, Jose Antonio Iribarren, María Rivero, Piedad Arazo, Félix Gutiérrez, CoRIS Study Group
BACKGROUND: The objetive was investigate the long-term impact of low level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving ART. METHODS: We analyzed ART-naïve adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies/ml. LLV50-199 was defined as two consecutive VL between 50 and 199 copies/ml, and LLV200-499 as two consecutive VL between 50 and 499 copies/ml with at least one between 200 and 499 copies/ml...
March 13, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29542680/phoenixin-a-novel-brain-gut-skin-peptide-with-multiple-bioactivity
#7
REVIEW
Rong-Ming Lyu, Alan Cowan, Ying Zhang, Yi-Hung Chen, Siok L Dun, Jaw-Kang Chang, Nae J Dun, Jin Jun Luo
In this brief review we summarize the current fndings relative to the discovery of a small peptide ligand, phoenixin (PNX). Using a bioinformatic approach, two novel peptides PNX-14 and PNX-20 containing 14 and 20 amino acids, respectively, were isolated from diverse tissues including the brain, heart, lung and stomach. Mass spectrometry analysis identified a major and minor peak corresponding to PNX-14 and PNX-20, in rat or mouse spinal cord extracts. With the use of a rabbit polyclonal antiserum, phoenixin immunoreactivity (irPNX) was detected in discrete areas of the rodent brain including several hypothalamic subnuclei and dorsal motor nucleus of the vagus...
March 15, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29533818/culture-free-highly-sensitive-quantitative-detection-of-bacteria-from-minimally-processed-samples-using-fluorescence-imaging-by-smartphone
#8
Sajal Shrivastava, Won-Il Lee, Nae-Eung Lee
A critical unmet need in the diagnosis of bacterial infections, which remain a major cause of human morbidity and mortality, is the detection of scarce bacterial pathogens in a variety of samples in a rapid and quantitative manner. Herein, we demonstrate smartphone-based detection of Staphylococcus aureus in a culture-free, rapid, quantitative manner from minimally processed liquid samples using aptamer-functionalized fluorescent magnetic nanoparticles. The tagged S. aureus cells were magnetically captured in a detection cassette, and then fluorescence was imaged using a smartphone camera with a light-emitting diode as the excitation source...
March 6, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29525790/race-ethnicity-dietary-acid-load-and-risk-of-end-stage-renal-disease-among-us-adults-with-chronic-kidney-disease
#9
Deidra C Crews, Tanushree Banerjee, Donald E Wesson, Hal Morgenstern, Rajiv Saran, Nilka Ríos Burrows, Desmond E Williams, Neil R Powe
BACKGROUND: Dietary acid load (DAL) contributes to the risk of CKD and CKD progression. We sought to determine the relation of DAL to racial/ethnic differences in the risk of end-stage renal disease (ESRD) among persons with CKD. METHODS: Among 1,123 non-Hispanic black (NHB) and non-Hispanic white (NHW) National Health and Nutrition Examination Survey III participants with estimated glomerular filtration rate 15-59 mL/min/1.73 m2, DAL was estimated using the Remer and Manz net acid excretion (NAEes) formula and 24-h dietary recall...
March 9, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29488140/health-promoting-behaviors-benefit-the-mental-health-of-cirrhotic-outpatients
#10
Hui-Chuan Huang, Kuan-Chia Lin, Chia-Shin Wu, Nae-Fang Miao, Ming-Yao Chen
PURPOSE: The objectives of this study were to survey the frequency of engaging in a health-promoting lifestyle in patients with liver cirrhosis, and examine the mediating effects of a health-promoting lifestyle on relationships of symptoms and psychological distress with the quality of life (QOL). METHODS: A cross-sectional study was conducted to recruit 148 cirrhotic outpatients from the gastroenterology outpatient department of one medical university hospital...
February 27, 2018: Quality of Life Research
https://www.readbyqxmd.com/read/29482598/human-induced-pluripotent-stem-cell-derived-macrophages-and-their-immunological-function-in-response-to-tuberculosis-infection
#11
Danping Hong, Jiongyan Ding, Ouyang Li, Quan He, Minxia Ke, Mengyi Zhu, Lili Liu, Wen-Bin Ou, Yulong He, Yuehong Wu
BACKGROUND: Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. METHODS: In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control...
February 26, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29480882/delayed-diagnosis-of-xanthogranulomatous-pyelonephritis-in-a-quadriplegic-patient-with-uncontrolled-cutaneous-fistula-a-case-report
#12
Jae-Hyuk Yang, Jin Yong Shin, Si-Gyun Roh, Suk-Choo Chang, Nae-Ho Lee
RATIONALE: Xanthogranulomatous pyelonephritis (XGP) is a chronic destructive granulomatous inflammation that is characterized by urinary tract obstruction and invasion of the renal parenchyma. Although rare, XGP can lead to fatal complications, including perinephric inflammation, psoas abscess, and cutaneous fistula. PATIENT CONCERNS: A quadriplegic patient initially presented to the hospital with a chronic open wound and cutaneous fistula. DIAGNOSES: Abdominal computed tomography revealed a renal obstructing stone and enlarged right kidney with a perinephric fluid collection that communicated with the cutaneous fistula...
January 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29473944/non-endocannabinoid-n-acylethanolamines-and-2-monoacylglycerols-in-the-intestine
#13
REVIEW
Harald S Hansen, Vasiliki Vana
This review focuses on recent findings of the physiological and pharmacological role of non-endocannabinoid NAEs and 2-MAGs in the intestine and their involvement in the gut-brain signaling. Dietary fat suppress food intake and much research concerns the known gut peptides e.g. GLP-1, and CCK. NAEs and 2-MAGs represent another class of local gut signals most probably involved in the regulation of food intake. We discuss the putative biosynthetic pathways and targets of NAEs in the intestine as well as their anorectic role and changes in intestinal levels depending on the nutritional status...
February 23, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29464016/inhibition-of-the-nedd8-conjugation-pathway-induces-calcium-dependent-compensatory-activation-of-the-pro-survival-mek-erk-pathway-in-acute-lymphoblastic-leukemia
#14
Shuhua Zheng, Gilles M Leclerc, Bin Li, Ronan T Swords, Julio C Barredo
De novo and acquired drug resistance and subsequent relapse remain major challenges in acute lymphoblastic leukemia (ALL). We previously identified that pevonedistat (TAK-924, MLN4924), a first-in-class inhibitor of NEDD8 activating enzyme (NAE), elicits ER stress and has potent in vitro and in vivo efficacy against ALL. However, in pevonedistat-treated ALL cell lines, we found consistent activation of the pro-survival MEK/ERK pathway, which has been associated with relapse and poor outcome in ALL. We uncovered that inhibition of the MEK/ERK pathway in vitro and in vivo sensitized ALL cells to pevonedistat...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29436743/plasma-n-acylethanolamine-and-endocannabinoid-levels-in-burning-mouth-syndrome-potential-role-in-disease-pathogenesis
#15
Alison Barry, Ken D O'Halloran, Joseph P McKenna, Christine McCreary, Brendan Harhen, Daniel M Kerr, David P Finn, Eric J Downer
OBJECTIVE: The objective was to measure endocannabinoid (eCB) ligands and non-cannabinoid N-acylethanolamine (NAE) molecules in plasma from individuals with burning mouth syndrome (BMS), and to determine if plasma eCB/NAE levels correlated with pain, inflammation and depressive symptomatology in this cohort. STUDY DESIGN: Plasma content of the eCBs, anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), and the NAE molecules, palmitoylethanolamide (PEA) and oleolylethanolamide (OEA), were assessed in healthy subjects (n=8) and in a cohort of newly diagnosed BMS patients (n=9) using liquid chromatography-tandem mass spectrometry...
February 13, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29433564/high-dose-thiotepa-related-neurotoxicity-and-the-role-of-tramadol-in-children
#16
Christophe Maritaz, Francois Lemare, Agnes Laplanche, Sylvie Demirdjian, Dominique Valteau-Couanet, Christelle Dufour
BACKGROUND: Serious neurological adverse events (NAE) have occurred during treatment with high-dose thiotepa regimens of children with high-risk solid tumours. The objective was to assess the incidence of NAE related to high-dose thiotepa and to identify potential contributing factors that could exacerbate the occurrence of this neurotoxicity. METHODS: From May 1987 to March 2011, children with solid tumours treated with high-dose thiotepa were retrospectively identified...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29392596/team-based-health-information-exchange-use-increased-mammography-documentation-and-referral-in-an-academic-primary-care-practice-an-interrupted-time-series
#17
Samantha I Pitts, Nisa M Maruthur, Xiao Wang, Melinda D Sawyer, Renee Grimes, Candace Nigrin, Jeanne M Clark, Nae-Yuh Wang, Heather F Sateia, Kimberly S Peairs
BACKGROUND: Few studies have examined the impact of health information exchanges (HIE) on quality in ambulatory settings. METHODS: From September 29, 2014, to September 4, 2015, we conducted an interrupted time series analysis of query-based use of the state HIE as part of team-based care to improve mammography screening in an academic primary care practice. Women aged 50-74 years with a practice visit and who were eligible for mammography were included. We conducted non-parametric data analysis using LOESS, followed by ARIMA analysis...
February 1, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29391311/shorter-waiting-times-from-education-to-colonoscopy-can-improve-the-quality-of-bowel-preparation-a-randomized-controlled-trial
#18
Jin Lee, Tae Oh Kim, Joo Wan Seo, Joon Hyuk Choi, Nae Yun Heo, Jongha Park, Seung Ha Park, Sung Yeon Yang, Young Soo Moon
BACKGROUND/AIMS: Adequate bowel preparation is essential for an effective and safe colonoscopy. This study aimed to evaluate the quality of bowel preparation according to waiting times from education to colonoscopy. MATERIALS AND METHODS: A prospective, investigator-blinded, randomized study was performed from December 2016 to March 2017. Patients were divided into two groups: within 2 weeks (group A, n=64) or more than 2 weeks (group B, n=66) from education about bowel preparation to colonoscopy...
January 2018: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/29387232/mln4924-neddylation-inhibitor-promotes-cell-death-in-paclitaxel-resistant-human-lung-adenocarcinoma-cells
#19
Qiang Xu, Guibin Lin, Huizhe Xu, Lulu Hu, Yupeng Wang, Sha Du, Wuguo Deng, Wenxian Hu, Wei Cheng, Ke Jiang
Acquired resistance to first-line chemotherapeutics, including paclitaxel (PTX), is a primary factor contributing to chemotherapy failure in non-small cell lung cancer (NSCLC) patients. Previous studies have identified that targeting NEDD8-activating enzyme (NAE) with MLN4924 effectively overcomes platinum resistance in preclinical models of ovarian cancer. However, the underlying mechanisms are yet to be fully elucidated. The present study demonstrates that the inhibition of the neddylation pathway with MLN4924 an NAE inhibitor inhibited protein neddylation, inactivated cullin-RING E3 ligase and exhibited a potent antiproliferative effect on PTX-resistant A549 and H460 cells (A549/PTX and H460/PTX)...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29348517/ndrg2-contributes-to-cisplatin-sensitivity-through-modulation-of-bak-to-mcl-1-ratio
#20
Soojong Park, Sang-Seok Oh, Ki Won Lee, Yeon-Kyeong Lee, Nae Yu Kim, Joo Heon Kim, Jiyun Yoo, Kwang Dong Kim
The downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be associated with the progression and poor prognosis of several cancers. Sensitivity to anti-cancer may be associated with a good prognosis in cancer patients, and NDRG2, which is induced by p53, sensitizes the cells to chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis under chemotreatment has not been sufficiently studied. In this study, we investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53...
January 18, 2018: Cell Death & Disease
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