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https://www.readbyqxmd.com/read/29156772/stat3-and-stat5a-are-potential-therapeutic-targets-in-castration-resistant-prostate-cancer
#1
Sambit K Mohanty, Kader Yagiz, Dinesh Pradhan, Daniel J Luthringer, Mahul B Amin, Serhan Alkan, Bekir Cinar
Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156771/novel-post-transcriptional-and-post-translational-regulation-of-pro-apoptotic-protein-bok-and-anti-apoptotic-protein-mcl-1-determine-the-fate-of-breast-cancer-cells-to-survive-or-die
#2
Benjamin Onyeagucha, Panneerdoss Subbarayalu, Nourhan Abdelfattah, Subapriya Rajamanickam, Santosh Timilsina, Rosa Guzman, Carla Zeballos, Vijay Eedunuri, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, Ratna K Vadlamudi, Manjeet K Rao
Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156765/network-directed-cis-mediator-analysis-of-normal-prostate-tissue-expression-profiles-reveals-downstream-regulatory-associations-of-prostate-cancer-susceptibility-loci
#3
Nicholas B Larson, Shannon K McDonnell, Zach Fogarty, Melissa C Larson, John Cheville, Shaun Riska, Saurabh Baheti, Alexandra M Weber, Asha A Nair, Liang Wang, Daniel O'Brien, Jaime Davila, Daniel J Schaid, Stephen N Thibodeau
Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis-acting associations due to study limitations. While trans-eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans-eQTL associations are mediated by cis-regulated genes, such as transcription factors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156760/microrna-29a-increased-the-intestinal-membrane-permeability-of-colonic-epithelial-cells-in-irritable-bowel-syndrome-rats
#4
Guanqun Chao, Yingying Wang, Shuo Zhang, Weilin Yang, Zheying Ni, Xuliang Zheng
Background: The whole pathogenesis of diarrhea-predominant irritable bowel syndrome(IBS-D) is poorly understood. Our goal was to evaluate the expression change of microRNA-29a(miR-29a) in colonic epithelial cells in IBS rats and clarify the mechanism of miR-29a increasing the intestinal membrane permeability through aquaporins(AQPs). Methods: The IBS-D rats models were induced by rectal distention pressure combining with extremities constraint. The colonic epithelial cells were divided into four groups...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156729/a-rasgap-dab2ip-regulates-lipid-droplet-homeostasis-by-serving-as-gap-toward-rab40c
#5
Xiaomin Luo, Chunman Li, Ran Tan, Xiaohui Xu, William K K Wu, Ayano Satoh, Tuanlao Wang, Sidney Yu
Lipid droplet (LD) homeostasis involves activities of various RAB small GTPases. Recently, we found RAB40C was one of the RAB proteins regulating LD homeostasis. RAB40C contains a unique SOCS domain that is required for clustering of LDs. However, its precise functional role in LD homeostasis and mechanism of regulation remain largely unknown. In this study, we observed over-accumulation of LDs in cells with RAB40C deleted by Crispr-Cas9 editing. RAB40C appeared to reduce LD accumulation after long term incubation of cells with oleic acid (24 hours)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156723/effects-of-pharmacological-gap-junction-and-sodium-channel-blockade-on-s1s2-restitution-properties-in-langendorff-perfused-mouse-hearts
#6
Gary Tse, Tong Liu, Guangping Li, Wendy Keung, Jie Ming Yeo, Yin Wah Fiona Chan, Bryan P Yan, Yat Sun Chan, Sunny Hei Wong, Ronald A Li, Jichao Zhao, William K K Wu, Wing Tak Wong
Gap junctions and sodium channels are the major molecular determinants of normal and abnormal electrical conduction through the myocardium, however, their exact contributions to arrhythmogenesis are unclear. We examined conduction and recovery properties of regular (S1) and extrasystolic (S2) action potentials (APs), S1S2 restitution and ventricular arrhythmogenicity using the gap junction and sodium channel inhibitor heptanol (2 mM) in Langendorff-perfused mouse hearts (n=10). Monophasic action potential recordings obtained during S1S2 pacing showed that heptanol increased the proportion of hearts showing inducible ventricular tachycardia (0/10 vs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156715/connective-tissue-growth-factor-mediates-tgf-%C3%AE-1-induced-low-grade-serous-ovarian-tumor-cell-apoptosis
#7
Jung-Chien Cheng, Hsun-Ming Chang, Peter C K Leung
Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156685/whole-genome-and-transcriptome-analysis-reveal-maldi-tof-ms-and-sds-page-have-limited-performance-for-the-detection-of-the-key-outer-membrane-protein-in-carbapenem-resistant-klebsiella-pneumoniae-isolates
#8
Naina Adren Pinto, Roshan D'Souza, In Sik Hwang, Jongrak Choi, Yong Ha In, Hyung Soon Park, Choong-Min Ryu, Dongeun Yong, Kyungwon Lee
To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant Klebsiella pneumoniae was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36. MALDI-TOF MS showed peaks at ∼36 and ∼38 kDa that corresponded to OmpA and OmpK36, respectively. In all the strains except YMC2014/03/P345, the ∼38 kDa peaks were present...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#9
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156670/chipping-in-on-clonal-hematopoiesis
#10
EDITORIAL
Nancy K Gillis, Eric Padron
No abstract text is available yet for this article.
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156634/an-overview-of-chitosan-nanoparticles-and-its-application-in-non-parenteral-drug-delivery
#11
REVIEW
Munawar A Mohammed, Jaweria T M Syeda, Kishor M Wasan, Ellen K Wasan
The focus of this review is to provide an overview of the chitosan based nanoparticles for various non-parenteral applications and also to put a spotlight on current research including sustained release and mucoadhesive chitosan dosage forms. Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary use and approved for wound dressing applications. Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration. Chitosan has chemical functional groups that can be modified to achieve specific goals, making it a polymer with a tremendous range of potential applications...
November 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29156630/anti-bacteria-and-microecosystem-regulating-effects-of-dental-implant-coated-with-dimethylaminododecyl-methacrylate
#12
Bolei Li, Yang Ge, Yao Wu, Jing Chen, Hockin H K Xu, Minggang Yang, Mingyun Li, Biao Ren, Mingye Feng, Michael D Weir, Xian Peng, Lei Cheng, Xuedong Zhou
The effects of dimethylaminododecyl methacrylate (DMADDM) modified titanium implants on bacterial activity and microbial ecosystem of saliva-derived biofilm were investigated for the first time. Titanium discs were coated with DMADDM solutions at mass fractions of 0 mg/mL (control), 1, 5 and 10 mg/mL, respectively. Biomass accumulation and metabolic activity of biofilms were tested using crystal violet assay and MTT (3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 16S rRNA gene sequencing was performed to measure the microbial community...
November 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29156606/synthesis-and-in-vitro-cytotoxicity-of-the-4-halogenoanilino-6-bromoquinazolines-and-their-6-4-fluorophenyl-substituted-derivatives-as-potential-inhibitors-of-epidermal-growth-factor-receptor-tyrosine-kinase
#13
Malose Jack Mphahlele, Hugues K Paumo, Yee Siew Choong
Series of the 2-unsubstituted and 2-(4-chlorophenyl)-substituted 4-anilino-6-bromoquinazolines and their 6-(4-fluorophenyl)-substituted derivatives were evaluated for in vitro cytotoxicity against MCF-7 and HeLa cells. The 2-unsubstituted 4-anilino-6-bromoquinazolines lacked activity, whereas most of their 2-(4-chlorophenyl) substituted derivatives were found to exhibit significant cytotoxicity and selectivity against HeLa cells. Replacement of bromine with 4-fluorophenyl group for the 2-unsubstituted 4-anilinoquinazolines resulted in superior activity against HeLa cells compared to Gefitinib...
November 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29156592/activation-of-trek-1-but-not-trek-2-channel-by-mood-stabilizers
#14
Eun-Jin Kim, Dong Kun Lee, Seong-Geun Hong, Jaehee Han, Dawon Kang
Earlier studies have demonstrated that the tandem pore domain weak inward rectifying K⁺ channel (TWIK)-related K⁺ (TREK)-1 channel is inhibited by antidepressants and is associated with major depression. However, little is known about the effect of mood stabilizers that are commonly used for treatment of bipolar disorder on TREK channels, members of the two-pore domain K⁺ (K2P) channel family. This study sought to investigate the effect of mood stabilizers on TREK-1 and TREK-2 channels. HEK-293A cells were transfected with human TREK-1 or TREK-2 DNA...
November 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156544/endogenous-sphingolipid-signaling-pathway-implicated-in-the-action-of-croton-membranaceus-on-the-prostate-gland-in-bph-patients
#15
George Awuku Asare, Yvonne Anang, Daniel K Afriyie, Brodrick Yeboah Amoah, Bernice Asiedu, Derek Doku, Hannah Serwah Ocansey, Nana Yaw Odei Danso, Prince Tekpor, Sarah Osam
Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH) who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA), lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1) and 2 (SphK2), sphingosine lyase (SPL), the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE) and malondialdehyde (MDA), were determined...
November 18, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29156543/efficiency-of-true-green-light-emitting-diodes-non-uniformity-and-temperature-effects
#16
Ilya E Titkov, Sergey Yu Karpov, Amit Yadav, Denis Mamedov, Vera L Zerova, Edik Rafailov
External quantum efficiency of industrial-grade green InGaN light-emitting diodes (LEDs) has been measured in a wide range of operating currents at various temperatures from 13 K to 300 K. Unlike blue LEDs, the efficiency as a function of current is found to have a multi-peak character, which could not be fitted by a simple ABC-model. This observation correlated with splitting of LED emission spectra into two peaks at certain currents. The characterization data are interpreted in terms of non-uniformity of the LED active region, which is tentatively attributed to extended defects like V-pits...
November 18, 2017: Materials
https://www.readbyqxmd.com/read/29156446/who-is-watching-user-generated-alcohol-posts-on-social-media
#17
Eilin K Erevik, Ståle Pallesen, Cecilie S Andreassen, Øystein Vedaa, Torbjørn Torsheim
AIM: To examine students' exposure to user-generated alcohol content on social media, and identify characteristics (i.e. demographics, personality traits, alcohol use, alcohol-related cognitions, and social media factors) associated with monthly or more frequent exposure. METHOD: College/university students (N=11,236) in Bergen, Norway, completed a web-survey measuring exposure to alcohol on social media - both frequency and interpretations of alcohol content. The survey included questions regarding demographics, personality, alcohol-related cognitions, and general use of social media and alcohol...
November 14, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/29156433/evaluating-features-of-periphytic-diatom-communities-as-biomonitoring-tools-in-fresh-brackish-and-marine-waters
#18
Lalit K Pandey, Yogesh Chandra Sharma, Jihae Park, Soyeon Choi, Hojun Lee, Jie Lyu, Taejun Han
The aims of this study were to assess the biodiversity of periphytic diatom assemblages in fresh, brackish and marine waterbodies of Korea, and to assess the effect of environmental and anthropogenic factors on parameters such as the quantity and biovolume of lipid bodies and deformations of diatoms as early warning measures of anthropogenic impact. Diatom samples were collected from 31 sites (14 freshwater, 10 brackish and 7 marine), which included less impacted (upstream) and impacted (downstream) sites in each water type...
November 10, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#19
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29156380/structure-based-design-of-herg-neutral-antihypertensive-oxazalone-and-imidazolone-derivatives
#20
Busecan Aksoydan, Isik Kantarcioglu, Ismail Erol, Ramin Ekhteiari Salmas, Serdar Durdagi
Angiotensin II receptor type 1 (AT1) antagonists are the most recent drug class against hypertension. Recently first crystal structure of AT1 receptor is deposited to the protein data bank (PDB ID: 4YAY). In this work, several molecular screening methods such as molecular docking and de novo design studies were performed and it is found that oxazolone and imidazolone derivatives reveal similar/better interaction energy profiles compared to the FDA approved sartan molecules at the binding site of the AT1 receptor...
October 18, 2017: Journal of Molecular Graphics & Modelling
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