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https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#1
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28433938/imaging-lysosomal-highly-reactive-oxygen-species-and-lighting-up-cancer-cells-and-tumors-enabled-by-a-si-rhodamine-based-near-infrared-fluorescent-probe
#2
Hongxing Zhang, Jing Liu, Chenlu Liu, Pengcheng Yu, Minjia Sun, Xiaohan Yan, Jian-Ping Guo, Wei Guo
Lysosomes have recently been regarded as the attractive pharmacological targets for selectively killing of cancer cells via lysosomal cell death (LCD) pathway that is closely associated with reactive oxygen species (ROS). However, the details on the ROS-induced LCD of cancer cells are still poorly understood, partially due to the absence of a lysosome-targetable, robust, and biocompatible imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based fluorescent probe, named PSiR, which could selectively and sensitively image the pathologically more relavent highly reactive oxygen species (hROS: HClO, HO, and ONOO(-)) in lysosomes of cancer cells...
April 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28430560/database-centric-method-for-automated-high-throughput-deconvolution-and-analysis-of-kinetic-antibody-screening-data
#3
R Paul Nobrega, Michael Brown, Cody Williams, Chris Sumner, Patricia Estep, Isabelle Caffry, Yao Yu, Heather Lynaugh, Irina Burnina, Asparouh Lilov, Jordan Desroches, John Bukowski, Tingwan Sun, Jonathan P Belk, Kirt Johnson, Yingda Xu
The state-of-the-art industrial drug discovery approach is the empirical interrogation of a library of drug candidates against a target molecule. The advantage of high-throughput kinetic measurements over equilibrium assessments is the ability to measure each of the kinetic components of binding affinity. Although high-throughput capabilities have improved with advances in instrument hardware, three bottlenecks in data processing remain: (1) intrinsic molecular properties that lead to poor biophysical quality in vitro are not accounted for in commercially available analysis models, (2) processing data through a user interface is time-consuming and not amenable to parallelized data collection, and (3) a commercial solution that includes historical kinetic data in the analysis of kinetic competition data does not exist...
April 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28430437/discovery-of-an-hcv-ns5b-replicase-palm-site-allosteric-inhibitor-bms-929075-advanced-to-phase-1-clinical-studies
#4
Kap-Sun Yeung, Brett R Beno, Kyle Parcella, John A Bender, Katherine A Grant-Young, Andrew Nickel, Prashantha Gunaga, Prakash Anjanappa, Rajesh Onkardas Bora, Kumaravel Selvakumar, Karen Rigat, Ying-Kai Wang, Mengping Liu, Julie A Lemm, Kathy Mosure, Steven Sheriff, Changhong Wan, Mark Witmer, Kevin Kish, Umesh M Hanumegowda, Xiaoliang Zhuo, Yue-Zhong Shu, Dawn Parker, Roy Haskell, Alicia Ng, Qi Gao, Elizabeth Colston, Joseph Raybon, Dennis M Grasela, Kenneth S Santone, Min Gao, Nicholas A Meanwell, Michael W Sinz, Matthew G Soars, Jay O Knipe, Susan B Roberts, John F Kadow
The hepatitis C virus NS5B replicase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Inspired by the overlay of bound structures of three structurally distinct NS5B palm site allosteric inhibitors, the high throughput screening hit anthranilic acid 4, the known benzofuran analog 5 and the benzothiadiazine derivative 6, an optimization process utilizing the simple benzofuran template 7 as a starting point for a fragment growing approach was pursued...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430435/cu-in-halide-perovskite-cihp-solar-absorbers
#5
Xin-Gang Zhao, Dongwen Yang, Yuanhui Sun, Tianshu Li, Lijun Zhang, Liping Yu, Alex Zunger
The long-term chemical instability and the presence of toxic Pb in otherwise stellar solar absorber APbX3 made of organic molecules on the A site and halogens for X have hindered their large-scale commercialization. Previously explored ways to achieve Pb-free halide perovskites involved replacing Pb(2+) with other similar M(2+) cations in ns(2) electron configuration, e.g., Sn(2+) or by Bi(3+) (plus Ag(+)), but unfortunately this showed either poor stability (M = Sn) or weakly absorbing oversized indirect gaps (M = Bi), prompting concerns that perhaps stability and good optoelectronic properties might be contraindicated...
April 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28428752/desensitizing-mitochondrial-permeability-transition-by-erk-cyclophilin-d-axis-contributes-to-the-neuroprotective-effect-of-gallic-acid-against-cerebral-ischemia-reperfusion-injury
#6
Jing Sun, Da-Dui Ren, Jin-Yi Wan, Chen Chen, Dong Chen, Huan Yang, Chun-Lai Feng, Jing Gao
Ischemic stroke is a devastating disease with complex pathophysiology. Much evidence confirms that opening of the mitochondrial permeability transition pore (MPTP) is related with mitochondrial dysfunction to apoptosis in ischemic stroke, thus elucidating its signaling mechanism and screening novel MPTP inhibitor is therefore of paramount importance. Our earlier studies identified that gallic acid (GA), a naturally occurring plant phenol, endows with effect on inhibition of mitochondrial dysfunction, which has significant neuroprotective effect in cerebral ischemia/reperfusion injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428157/texting-and-mobile-phone-app-interventions-for-improving-adherence-to-preventive-behavior-in-adolescents-a-systematic-review
#7
Sherif M Badawy, Lisa M Kuhns
BACKGROUND: Many preventable behaviors contribute to adolescent mortality and morbidity. Non-adherence to preventive measures represents a challenge and has been associated with worse health outcomes in this population. The widespread use of electronic communication technologies by adolescents, particularly the use of text messaging (short message service, SMS) and mobile phones, presents new opportunities to intervene on risk and preventive risk behavior, but little is known about their efficacy...
April 19, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/28427443/benserazide-a-dopadecarboxylase-inhibitor-suppresses-tumor-growth-by-targeting-hexokinase-2
#8
Wei Li, Mengzhu Zheng, Shuangping Wu, Suyu Gao, Mei Yang, Zhimei Li, Qiuxia Min, Weiguang Sun, Lixia Chen, Guangya Xiang, Hua Li
BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy. METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28427191/down-regulation-of-long-non-coding-rna-rp11-708h21-4-is-associated-with-poor-prognosis-for-colorectal-cancer-and-promotes-tumorigenesis-through-regulating-akt-mtor-pathway
#9
Longci Sun, Chunhui Jiang, Chunjie Xu, Hanbing Xue, Hong Zhou, Lei Gu, Ye Liu, Qing Xu
Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and progression. Herein, through next generation RNA sequencing and experimental validations, we determined the expression status of RP11-708H21.4 in colorectal cancer (CRC) and explored its clinical significance and biological functions in CRC. Differentially expressed lncRNAs from CRC samples and corresponding normal mucosa tissues was screened through RNA sequencing, and RP11-708H21.4 was selected for further experimental validation...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426808/a-screen-for-protective-drugs-against-delayed-hypoxic-injury
#10
Chun-Ling Sun, Huiliang Zhang, Meng Liu, Wang Wang, C Michael Crowder
Despite longstanding efforts to develop cytoprotective drugs against ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to treat hypoxic injury. The failure of traditional strategies at solving this problem suggests the need for novel and unbiased approaches that can lead to previously unsuspected targets and lead compounds. Towards this end, we report here a unique small molecule screen in the nematode C. elegans for compounds that improve recovery when applied after the hypoxic insult, using a C...
2017: PloS One
https://www.readbyqxmd.com/read/28425521/chemical-genomic-analysis-of-gpr35-signaling
#11
Heidi Haibei Hu, Huayun Deng, Shizhang Ling, Haiyan Sun, Terry Kenakin, Xinmiao Liang, Ye Fang
GPR35, a family A orphan G protein-coupled receptor, has been implicated in inflammatory, neurological, and cardiovascular diseases. However, not much is known about the signaling and functions of GPR35. We performed a label-free kinome short hairpin RNA screen and identified a putative signaling network of GPR35 in HT-29 cells, some of which was validated using gene expression, biochemical and cellular assays. The results showed that GPR35 induced hypoxia-inducible factor 1α, and was involved in synaptic transmission, sensory perception, the immune system, and morphogenetic processes...
April 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28423593/anti-cancer-effect-of-novel-pak1-inhibitor-via-induction-of-puma-mediated-cell-death-and-p21-mediated-cell-cycle-arrest
#12
Tae-Gyun Woo, Min-Ho Yoon, Shin-Deok Hong, Jiyun Choi, Nam-Chul Ha, Hokeun Sun, Bum-Joon Park
Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423513/mir-503-5p-confers-drug-resistance-by-targeting-puma-in-colorectal-carcinoma
#13
Ke Xu, Guo Chen, Yanyan Qiu, Zeting Yuan, Hongchang Li, Xia Yuan, Jian Sun, Jianhua Xu, Xin Liang, Peihao Yin
The development of multidrug-resistance (MDR) is a major contributor to death in colorectal carcinoma (CRC). Here, we investigated the possible role of microRNA (miR)-503-5p in drug resistant CRC cells. Unbiased microRNA array screening revealed that miR-503-5p is up-regulated in two oxaliplatin (OXA)-resistant CRC cell lines. Overexpression of miR-503-5p conferred resistance to OXA-induced apoptosis and inhibition of tumor growth in vitro and in vivo through down-regulation of PUMA expression. miR-503-5p knockdown sensitized chemoresistant CRC cells to OXA...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421123/study-of-the-hypoglycemic-activity-of-derivatives-of-isoflavones-from-cicer-arietinum-l
#14
Ying Wei, Pengshou Li, Bo Li, Jiaqi Gao, Dongchao Wang, Lingling Qin, Wen Sun, Yunling Xu, Haoxia Shi, Tunhai Xu, Tonghua Liu
The chickpea, a food and medicine used by the people of Xinjiang, has a beneficial hypoglycemic effect. To better utilize this national resource and develop hypoglycemic agents from components of the chickpea, a series of new derivatives of isoflavone compounds from the chickpea were synthesized. An insulin-resistant (IR) HepG2 cell model was used to screen the hypoglycemic activities of these compounds. And the structure-activity relationships of these compounds were explored. Additionally, several combinations of these compound displayed higher hypoglycemic activity than any single compound, and they had similar hypoglycemic activity to that of the positive control group (p > 0...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#15
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28420350/trends-in-baseline-cd4-cell-counts-and-risk-factors-for-late-antiretroviral-therapy-initiation-among-hiv-positive-patients-in-shanghai-a-retrospective-cross-sectional-study
#16
Jianjun Sun, Li Liu, Jiayin Shen, Panpan Chen, Hongzhou Lu
BACKGROUNDS: There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. METHODS: A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014...
April 19, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28418939/exploring-the-molecular-pathogenesis-and-biomarkers-of-high-risk-oral-premalignant-lesions-on-the-basis-of-long-noncoding-rna-expression-profiling-by-serial-analysis-of-gene-expression
#17
Hongcheng Jia, Xuan Wang, Zheng Sun
Oral premalignant lesions (OPLs) have malignant transformation potential, with no reliable markers available. This study aimed to assess molecular events to identify biomarkers that can reflect high-risk lesions as predictive factors to tailor clinical decision for patients on the basis of long noncoding RNAs (lncRNA) expression profiling by serial analysis of gene expression. The GSE31021 and GSE8127 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs were identified using the LIMMA package in R language...
April 17, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28418920/complementary-utility-of-targeted-next-generation-sequencing-and-immunohistochemistry-panels-as-a-screening-platform-to-select-targeted-therapy-for-advanced-gastric-cancer
#18
Hyo Song Kim, Hanna Lee, Su-Jin Shin, Seung-Hoon Beom, Minkyu Jung, Sujin Bae, Eun Young Lee, Kyu Hyun Park, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Woong Sub Koom, Joon Seok Lim, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Hyunki Kim, Soonmyung Paik
We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418496/homozygosity-mapping-and-genetic-analysis-of-autosomal-recessive-retinal-dystrophies-in-144-consanguineous-pakistani-families
#19
Lin Li, Yabin Chen, Xiaodong Jiao, Chongfei Jin, Dan Jiang, Mukesh Tanwar, Zhiwei Ma, Li Huang, Xiaoyin Ma, Wenmin Sun, Jianjun Chen, Yan Ma, Oussama M'hamdi, Gowthaman Govindarajan, Patricia E Cabrera, Jiali Li, Nikhil Gupta, Muhammad Asif Naeem, Shaheen N Khan, Sheikh Riazuddin, Javed Akram, Radha Ayyagari, Paul A Sieving, S Amer Riazuddin, J Fielding Hejtmancik
Purpose: The Pakistan Punjab population has been a rich source for identifying genes causing or contributing to autosomal recessive retinal degenerations (arRD). This study was carried out to delineate the genetic architecture of arRD in the Pakistani population. Methods: The genetic origin of arRD in a total of 144 families selected only for having consanguineous marriages and multiple members affected with arRD was examined. Of these, causative mutations had been identified in 62 families while only the locus had been identified for an additional 15...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28418495/molecular-genetic-analysis-of-pakistani-families-with-autosomal-recessive-congenital-cataracts-by-homozygosity-screening
#20
Jianjun Chen, Qiwei Wang, Patricia E Cabrera, Zilin Zhong, Wenmin Sun, Xiaodong Jiao, Yabin Chen, Gowthaman Govindarajan, Muhammad Asif Naeem, Shaheen N Khan, Muhammad Hassaan Ali, Muhammad Zaman Assir, Fawad Ur Rahman, Zaheeruddin A Qazi, Sheikh Riazuddin, Javed Akram, S Amer Riazuddin, J Fielding Hejtmancik
Purpose: To identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population. Methods: Based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes...
April 1, 2017: Investigative Ophthalmology & Visual Science
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