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Yu-Ming Wang, Jeng-Wei Lu, Chang-Chi Lin, Yuan-Fan Chin, Tzong-Yuan Wu, Liang-In Lin, Zheng-Zong Lai, Szu-Cheng Kuo, Yi-Jung Ho
Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro...
October 11, 2016: Antiviral Research
Juan Zhao, Qiushan He, Zhimin Gong, Sen Chen, Long Cui
PURPOSE: To investigate the effects of anthelminthic drug niclosamide in renal cell carcinoma (RCC) and the underlying mechanisms of its action. METHODS: The effects of niclosamide on the proliferation and apoptosis of RCC cells were examined in vitro and in vivo by using MTS, colony formation assay, flow cytometry and xenograft cancer mouse model. Mechanism studies were performed by analyzing Wnt/β-catenin signaling and mitochondrial functions in a panel of RCC cell lines...
2016: SpringerPlus
Major Gooyit, Kim D Janda
Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen...
2016: Scientific Reports
Ni Ai, Richard D Wood, Eric Yang, William J Welsh
PURPOSE: Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in modulating aberrant glutamate transmission in NP. METHOD: Calcium mobilization assays and cross-receptor selectivity experiments are conducted to characterize the pharmacological activity of niclosamide...
September 8, 2016: Pharmaceutical Research
Florence Morin, Niloufar Kavian, Carole Nicco, Olivier Cerles, Christiane Chéreau, Frédéric Batteux
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide...
September 9, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Miao Xu, Emily M Lee, Zhexing Wen, Yichen Cheng, Wei-Kai Huang, Xuyu Qian, Julia Tcw, Jennifer Kouznetsova, Sarah C Ogden, Christy Hammack, Fadi Jacob, Ha Nam Nguyen, Misha Itkin, Catherine Hanna, Paul Shinn, Chase Allen, Samuel G Michael, Anton Simeonov, Wenwei Huang, Kimberly M Christian, Alison Goate, Kristen J Brennand, Ruili Huang, Menghang Xia, Guo-Li Ming, Wei Zheng, Hongjun Song, Hengli Tang
In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures...
October 2016: Nature Medicine
Fatemeh Ostadhossein, Santosh K Misra, Prabuddha Mukherjee, Alireza Ostadhossein, Enrique Daza, Saumya Tiwari, Shachi Mittal, Mark C Gryka, Rohit Bhargava, Dipanjan Pan
Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host-guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization...
August 22, 2016: Small
Diego Carrella, Isabella Manni, Barbara Tumaini, Rosanna Dattilo, Federica Papaccio, Margherita Mutarelli, Francesco Sirci, Carla A Amoreo, Marcella Mottolese, Manuela Iezzi, Laura Ciolli, Valentina Aria, Roberta Bosotti, Antonella Isacchi, Fabrizio Loreni, Alberto Bardelli, Vittorio E Avvedimento, Diego di Bernardo, Luca Cardone
The discovery of inhibitors for oncogenic signalling pathways remains a key focus in modern oncology, based on personalized and targeted therapeutics. Computational drug repurposing via the analysis of FDA-approved drug network is becoming a very effective approach to identify therapeutic opportunities in cancer and other human diseases. Given that gene expression signatures can be associated with specific oncogenic mutations, we tested whether a "reverse" oncogene-specific signature might assist in the computational repositioning of inhibitors of oncogenic pathways...
August 16, 2016: Oncotarget
Genna R Prather, James A MacLean, Mingxin Shi, Daniel K Boadu, Marilène Paquet, Kanako Hayashi
Endometriosis causes severe chronic pelvic pain and infertility. Because the standard medication and surgical treatments of endometriosis show high recurrence of symptoms, it is necessary to improve current treatment options. In the initial study, we examined whether niclosamide can be a useful drug for endometriosis in a preclinical setting. Endometriotic implants were induced using an established mouse model involving transimplantation of mouse endometrial fragments to the peritoneal wall of recipient mice...
August 17, 2016: Biology of Reproduction
Zhong Liu, Yong Li, Cao Lv, Li Wang, Hongping Song
Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase inhibitors (TKI), but becomes resistant to TKIs after it progresses to blast phase (BP). Here we show that niclosamide, a FDA-approved anthelmintic drug, enhances the sensitivity of BP-CML cells to dasatinib (2nd generation of BCR-ABL TKI) through inhibiting Erk/Mnk1/eIF4E signaling pathway. Niclosamide dose-dependently inhibits proliferation and induces apoptosis in a panel of CML cell lines. It also selectively targets BP-CML CD34 stem/progenitor cells through inducing apoptosis, inhibiting colony formation and self-renewal capacity while sparing normal bone marrow (NBM) counterparts...
September 16, 2016: Biochemical and Biophysical Research Communications
Megan B McConville, Terrance D Hubert, Christina K Remucal
The lampricides 3-trifluoromethyl-4-nitrophenol (TFM) and 2',5-dichloro-4'-nitrosalicylanilide (niclosamide) are directly added to many tributaries of the Great Lakes that harbor the invasive parasitic sea lamprey. Despite their long history of use, the fate of lampricides is not well understood. This study evaluates the rate and pathway of direct photodegradation of both lampricides under simulated sunlight. The estimated half-lives of TFM range from 16.6 ± 0.2 h (pH 9) to 32.9 ± 1.0 h (pH 6), while the half-lives of niclosamide range from 8...
September 20, 2016: Environmental Science & Technology
Youlin Deng, Zhongliang Wang, Fugui Zhang, Min Qiao, Zhengjian Yan, Qiang Wei, Jing Wang, Hao Liu, Jiaming Fan, Yulong Zou, Junyi Liao, Xue Hu, Liqun Chen, Xinyi Yu, Rex C Haydon, Hue H Luu, Hongbo Qi, Tong-Chuan He, Junhui Zhang
BACKGROUND/AIMS: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. METHODS: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry...
2016: Cellular Physiology and Biochemistry
Bei Jin, Chengyan Wang, Juan Li, Xin Du, Ke Ding, Jingxuan Pan
PURPOSE: Leukemia stem cells (LSCs), which are insensitive to tyrosine kinase inhibitors (TKIs), are an important source of TKI resistance and disease relapse in chronic myelogenous leukemia (CML). Obstacles to eradicating LSCs include limited understanding of the regulation network of LSCs. The present study aimed to examine the interplay between NF-κB and FOXM1/β-catenin, and the effect of its chemical intervention on CML LSCs. EXPERIMENTAL DESIGN: The interplay between NF-κB and FOXM1/β-catenin was analyzed by reciprocal co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assay in CML cells...
August 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tao Xiong, Qin Ping Zhao, Xing Jian Xu, Rong Liu, Ming Sen Jiang, Hui Fen Dong
A preparation of niclosamide named 50 % wettable powder of niclosamide ethanolamine salt (WPN), the only chemical molluscicide available in China, has been widely used for Oncomelania hupensis control over the past 20 years, but its molluscicidal mechanism has not been elucidated yet. Recently, a derivative of niclosamide, the salt of quinoid-2',5-dichloro-4'-nitro-salicylanilide (Liu Dai Shui Yang An, LDS), has been proven to have equivalent molluscicidal effects as WPN but with lower cost and significantly lower toxicity to fish than WPN...
November 2016: Parasitology Research
Mohammed A Suliman, Zhenxing Zhang, Heya Na, Ailton L L Ribeiro, Yu Zhang, Bachir Niang, Abdu Salim Hamid, Hua Zhang, Lijie Xu, Yunfei Zuo
Colorectal cancer (CRC) is among the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for the development of new therapeutic approaches for the treatment of CRC. Accumulating evidence has revealed that niclosamide, an anthelminthic drug, exerts antitumor activity in several types of cancer, including colon cancer. However, the underlying molecular mechanisms responsible for the effects of this drug remain elusive. Previous studies have shown that the aberrant Notch signaling pathway contributes to the carcinogenesis of colon cancer...
September 2016: International Journal of Molecular Medicine
Jin Meng, Xu-Tao Zhang, Xin-Li Liu, Lei Fan, Chen Li, Yang Sun, Xiao-Hua Liang, Jian-Bo Wang, Qi-Bing Mei, Feng Zhang, Tao Zhang
Williams syndrome transcription factor (WSTF), which is encoded by the BAZ1B gene, was first identified as a hemizygously deleted gene in patients with Williams syndrome. WSTF protein has been reported to be involved in transcription, replication, chromatin remodeling and DNA damage response, and also functions as a tyrosine protein kinase. However, the function of WSTF in cancer is not known. Here, we show that WSTF overexpression promotes proliferation, colony formation, migration and invasion of lung cancer A549 and H1299 cells...
November 2016: Cellular Signalling
Joseph E Ippolito, Matthew W Brandenburg, Xia Ge, Jan R Crowley, Kristopher M Kirmess, Avik Som, D Andre D'Avignon, Jeffrey M Arbeit, Samuel Achilefu, Kevin E Yarasheski, Jeffrey Milbrandt
Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6...
2016: PloS One
Florence Morin, Niloufar Kavian, Carole Nicco, Olivier Cerles, Christiane Chéreau, Frédéric Batteux
Sclerodermatous GVHD (Scl-GVHD), a frequent complication of allogeneic hematopoietic stem cell graft, shares many features with systemic sclerosis, such as production of autoantibodies and fibrosis of skin and inner organs. Recent reports on the implication of STAT3 and of Wnt/β-catenin in fibrosis have prompted us to investigate the effects of the inhibition of both signaling pathways in a mouse model of Scl-GVHD, using niclosamide an anthelmintic drug with well-defined safety profile. Scl-GVHD was induced in BALB/c mice by B10...
July 13, 2016: Journal of Investigative Dermatology
C Pavan Kumar, N Syaama Sundar, V Devi Prasad
An outbreak of immature paramphistomosis in Nellore Jodipi sheep was recorded in Nellore district of Andhra Pradesh in 158 sheep during the months of April-June-2012. The condition is diagnosed as immature paramphistomosis on the basis of symptoms, dung sample examination and necropsy findings. The infected sheep exhibited symptoms like persistent foetid, blackish diarrhoea, sub maxillary edema, dehydration and death. Necropsy findings include hemorrhagic thickening and necrosis of proximal duodenal mucosa, ascites, gelatinization of subcutaneous and renal fat...
June 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Raweerat Sitcharungsil, Dorn Watthanakulpanich
A 14-month-old female toddler presented with a 3-day history of pass- ing gravid proglottids of Taenia saginata. Neither she nor her family members had a history of eating raw beef or other raw meat. Single doses of praziquantel and niclosamide were administered. To the best of our knowledge, this is the youngest described patient with T. saginata infection to date.
May 2016: Southeast Asian Journal of Tropical Medicine and Public Health
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