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https://www.readbyqxmd.com/read/27878913/response-of-an-ovine-laryngeal-injury-model-to-a-novel-fibrosis-inhibitor
#1
Jacqueline Allen
BACKGROUND: Vocal fold injury results in severe voice alteration that limits occupational function and social interaction. An ovine model of laryngeal injury has been developed, validated and utilized to examine laryngeal wound healing and the effect of a novel collagen inhibitor (halofuginone) on surgical wound healing. The study design includes basic research and animal model. METHODS: An ovine laryngeal model was utilized to study controlled vocal fold injury and healing...
November 23, 2016: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/27798837/biochemical-and-structural-characterization-of-selective-allosteric-inhibitors-of-the-plasmodium-falciparum-drug-target-prolyl-trna-synthetase
#2
Stephen Nakazawa Hewitt, David M Dranow, Benjamin G Horst, Jan A Abendroth, Barbara Forte, Irene Hallyburton, Chimed Jansen, Beatriz Baragana, Ryan Choi, Kasey L Rivas, Matthew A Hulverson, Mitchell Dumais, Thomas E Edwards, Donald D Lorimer, Alan H Fairlamb, David W Gray, Kevin D Read, Adele M Lehane, Kiaran Kirk, Peter J Myler, Amy Wernimont, Christopher S J Walpole, Robin Stacy, Lynn K Barrett, Ian H Gilbert, Wesley C Van Voorhis
Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit PfProRS enzyme activity vs. H. sapiens (Hs) ProRS. X-ray crystallography structures were solved for apo, as well as substrate, and inhibitor bound forms of PfProRS. We identified two new inhibitors of PfProRS that bind outside the active site...
October 31, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27769022/tadalafil-reduces-airway-hyperactivity-and-protects-against-lung-and-respiratory-airways-dysfunction-in-a-rat-model-of-silicosis
#3
Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27709544/evaluation-and-elucidation-studies-of-natural-aglycones-for-anticancer-potential-using-apoptosis-related-markers-an-in-silico-study
#4
Salman Akhtar, M Kalim A Khan, Jamal M Arif
Exposure to exogenous and endogenous chemicals and subsequent cellular and molecular changes has been linked to enhanced cell proliferation and restricted apoptosis phenomenon. Though in the past decades numerous anticancer drugs inducing programmed cell death in cancer cells by targeting specific apoptotic markers have reached the market, they have been allied with unwanted side effects, ranging from mild to severe toxicity. With further understanding on the functional mechanism of p53 and MDM2 in apoptosis and in our continuous search for new and potent multi-target anticancer lead compounds, we have carried out molecular docking and inhibition studies of the selected aglycones along with selected anticancer leads, against the specific apoptotic and cell cycle markers using AutoDock Tools 4...
October 5, 2016: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/27687492/single-cell-analysis-reveals-igf-1-potentiation-of-inhibition-of-the-tgf-%C3%AE-smad-pathway-of-fibrosis-in-human-keratocytes-in-vitro
#5
Tomislav Sarenac, Martin Trapecar, Lidija Gradisnik, Marjan Slak Rupnik, Dusica Pahor
Corneal wound healing is often affected by TGF-β-mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27674657/the-mechanism-study-on-the-inhibition-effect-of-halofuginone-on-lung-cancer-cell-epithelial-mesenchymal-transition-induced-by-radiation-therapy
#6
Y Chen, Y Wang, N Liu, L Zhao
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27533085/halofuginone-inhibits-radiotherapy-induced-epithelial-mesenchymal-transition-in-lung-cancer
#7
Yang Chen, Weishuai Liu, Peng Wang, Hailing Hou, Ningbo Liu, Linlin Gong, Youyou Wang, Kai Ji, Lujun Zhao, Ping Wang
Radiotherapy is used to treat many different human tumors. Paradoxically, radiation can activate TGF-β1 signaling and induce the epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor progression. This study investigated the inhibitory effects of halofuginone, a plant-derived alkaloid that has been shown to inhibit TGF-β1 signaling, on radiation-induced EMT and explored the underlying mechanisms using a Lewis lung carcinoma (LLC) xenograft model. The cells and animals were divided into five treatment groups: Normal Control (NC), Halofuginone alone (HF), Radiotherapy alone (RT), Radiotherapy combined with Halofuginone (RT+HF), and Radiotherapy combined with the TGF-β1 inhibitor SB431542 (RT+SB)...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27518579/-clinical-epidemiology-of-cryptosporidiosis-in-calves
#8
S E Weber, C Lippuner, S Corti, P Deplazes, M Hässig
The aim of this study was to determine whether there is an association between Cryptosporidium infections in calves and immunological factors, as well as farm-related factors or the application of the anti-cryptosporidiosis drug Halofuginone. From January to June 2010, 63 cow-calf-pairs from 20 different farms near Zürich, Switzerland have been investigated. Each cowcalf- pair was visited three times within the first 6 weeks of life to collect data of the farm and animals, as well as blood, faecal, colostral and milk samples...
May 2016: Schweizer Archiv Für Tierheilkunde
https://www.readbyqxmd.com/read/27457799/amelioration-of-radiation-induced-lung-injury-by-halofuginone-an-experimental-study-in-wistar-albino-rats
#9
M Calik, G Yavas, S G Calik, C Yavas, Z E Celik, M F Sargon, H Esme
To evaluate effects of halofuginone (H) on radiation-induced lung injury (RILI), 60 rats were divided into six groups: Group (G) 1 control, G2 radiotherapy (RT) only, G3 and G4 2. 5 and 5 μg H and G5 and G6 RT + 2.5 and 5 μg H groups, respectively. A single dose of 12 Gy RT was given to both lungs. H was applied intraperitoneally with daily doses, until animals were killed at 6 and 16 weeks after RT. At 6th and 16th weeks of RT, five rats from each group were killed. Lung tissues were dissected for light and electron microscopy...
July 24, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27443201/a-multi-residue-method-for-17-anticoccidial-drugs-and-ractopamine-in-animal-tissues-by-liquid-chromatography-tandem-mass-spectrometry-and-time-of-flight-mass-spectrometry
#10
Johanna L Matus, Joe O Boison
A new and sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) method was developed and validated for the determination and confirmation of residues of 17 anticoccidials, plus free ractopamine in poultry muscle and liver, and bovine muscle, liver, and kidney tissues. The 17 anticoccidials are lasalocid, halofuginone, narasin, monensin, semduramicin, ethopabate, robenidine, buquinolate, toltrazuril as its sulfone metabolite, maduramicin, salinomycin, diclazuril, amprolium, decoquinate, dinitolmide, clopidol, and the nicarbazin metabolite DNC (N,N1-bis(4-nitrophenyl)urea)...
May 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27388880/halofuginone-alleviates-burn-induced-hepatic-and-renal-damage-in-rats
#11
Kivilcim Karadeniz Cerit, Berna Karakoyun, Meral Yüksel, Feriha Ercan, Halil Tuğtepe, Tolga E Dagli, Berrak Ç Yeğen
The aim of this study was to evaluate the possible protective effects of halofuginone on burn-induced oxidative injury of the liver and kidney. For the induction of burn, backs of Wistar albino rats were shaved and exposed for 10 seconds to water bath at 90°C, whereas rats in the control group were exposed for 10 seconds at 25°C. Rats were then administered either saline (1 ml/kg) or halofuginone (100 μg/kg/day) intraperitoneally and decapitated at the 24th hour (early burn) or on the 7th day (late burn)...
July 5, 2016: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/27385212/halofuginone-and-artemisinin-synergistically-arrest-cancer-cells-at-the-g1-g0-phase-by-upregulating-p21cip1-and-p27kip1
#12
Guoqing Chen, Ruihong Gong, Xianli Shi, Dajian Yang, Ge Zhang, Aiping Lu, Jianbo Yue, Zhaoxiang Bian
Combinational drug therapy is one of the most promising strategies in modern anticancer research. Traditional Chinese medicine (TCM) formulas represent a wealth of complex combinations proven successful over centuries of clinical application. One such formula used to treat a variety of diseases, including cancer, contains two herbs, whose main active components are Halofuginone (HF) and Artemisinin (ATS). Here we studied the anticancer synergism of HF and ATS in various cancer cell lines and in a xenograft nude mice model...
July 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27369778/therapeutic-elimination-of-the-type-1-interferon-receptor-for-treating-psoriatic-skin-inflammation
#13
Jun Gui, Michael Gober, Xiaoping Yang, Kanstantsin V Katlinski, Christine M Marshall, Meena Sharma, Victoria P Werth, Darren P Baker, Hallgeir Rui, John T Seykora, Serge Y Fuchs
Phototherapy with UV light is a standard treatment for psoriasis, yet the mechanisms underlying the therapeutic effects are not well understood. Studies in human and mouse keratinocytes and in the skin tissues from human patients and mice showed that UV treatment triggers ubiquitination and downregulation of the type I IFN receptor chain IFNAR1, leading to suppression of IFN signaling and an ensuing decrease in the expression of inflammatory cytokines and chemokines. The severity of imiquimod-induced psoriasiform inflammation was greatly exacerbated in skin of mice deficient in IFNAR1 ubiquitination (Ifnar1(SA))...
October 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27211859/simultaneous-pathway-activity-inference-and-gene-expression-analysis-using-rna-sequencing
#14
Daniel J O'Connell, Raivo Kolde, Matthew Sooknah, Daniel B Graham, Thomas B Sundberg, Isabel J Latorre, Tarjei S Mikkelsen, Ramnik J Xavier
Reporter gene assays are a venerable tool for studying signaling pathways, but they lack the throughput and complexity necessary to contribute to a systems-level understanding of endogenous signaling networks. We present a parallel reporter assay, transcription factor activity sequencing (TF-seq), built on synthetic DNA enhancer elements, which enables parallel measurements in primary cells of the transcriptome and transcription factor activity from more than 40 signaling pathways. Using TF-seq in Myd88(-/-) macrophages, we captured dynamic pathway activity changes underpinning the global transcriptional changes of the innate immune response...
May 25, 2016: Cell Systems
https://www.readbyqxmd.com/read/27197570/halofuginone-reduces-the-inflammatory-responses-of-dss-induced-colitis-through-metabolic-reprogramming
#15
Jing Liu, Hai-Tao Xiao, Hong-Sheng Wang, Huai-Xue Mu, Ling Zhao, Jun Du, Depo Yang, Dongmei Wang, Zhao-Xiang Bian, Shu-Hai Lin
Hypoxia and inflammation have been identified as the hallmarks of colitis, intertwined with metabolism. Here, we report that halofuginone (HF), an antiparasitic drug, attenuates dextran sulfate sodium (DSS)-induced colitis in mice, as represented by attenuating the disease activity index, inhibiting colonic shortening, ameliorating colonic lesions and histological signs of damage, reducing colonic myeloperoxidase activity, and suppressing the production of pro-inflammatory cytokines in colon tissue. Intriguingly, the hypoxia-inducible factor 1alpha (HIF-1α) and tumor necrosis factor alpha were also suppressed by HF treatment in colon tissues, exhibiting a tissue-specific effect...
June 21, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27130615/halofuginone-suppresses-growth-of-human-uterine-leiomyoma-cells-in-a-mouse-xenograft-model
#16
Faezeh Koohestani, Wenan Qiang, Amy L MacNeill, Stacy A Druschitz, Vanida A Serna, Malavika Adur, Takeshi Kurita, Romana A Nowak
STUDY QUESTION: Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? SUMMARY ANSWER: HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. WHAT IS KNOWN ALREADY: Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro...
July 2016: Human Reproduction
https://www.readbyqxmd.com/read/27021682/halofuginone-alleviates-acute-viral-myocarditis-in-suckling-balb-c-mice-by-inhibiting-tgf-%C3%AE-1
#17
Xiao-Hua Sun, Jia Fu, Da-Qing Sun
Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels...
April 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26963157/the-growing-pipeline-of-natural-aminoacyl-trna-synthetase-inhibitors-for-malaria-treatment
#18
COMMENT
Adélaïde Saint-Léger, Christopher Sinadinos, Lluís Ribas de Pouplana
Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P...
April 2, 2016: Bioengineered
https://www.readbyqxmd.com/read/26787922/anticoccidial-evaluation-of-a-traditional-chinese-medicine-brucea-javanica-in-broilers
#19
L Lan, B Zuo, H Ding, Y Huang, X Chen, A Du
The traditional Chinese medicinal plant Brucea javanica has received much attention for its significant antiprotozoal effects in recent years; however, little is known about its potential anticoccidial functions. In the present study, a series of experiments was conducted to investigate the prophylactic and therapeutic effects of ethanol extract from B. javanica on coccidiosis induced by Eimeria tenella in broiler chickens. Chickens infected with E. tenella were treated with B. javanica extract and compared either with broilers treated with the anticoccidial halofuginone hydrobromide (Stenorol) or with control groups that consisted of infected-unmedicated and uninfected-unmedicated broilers...
April 2016: Poultry Science
https://www.readbyqxmd.com/read/26787621/halofuginone-treatment-reduces-interleukin-17a-and-ameliorates-features-of-chronic-lung-allograft-dysfunction-in-a-mouse-orthotopic-lung-transplant-model
#20
Hisashi Oishi, Tereza Martinu, Masaaki Sato, Yasushi Matsuda, Shin Hirayama, Stephen C Juvet, Zehong Guan, Tomohito Saito, Marcelo Cypel, David M Hwang, Tracy L Keller, Malcolm R Whitman, Mingyao Liu, Shaf Keshavjee
BACKGROUND: Increasing evidence suggests that interleukin (IL)-17A plays an important role in chronic lung allograft dysfunction (CLAD), characterized by airway and lung parenchymal fibrosis, after lung transplantation. Halofuginone is a plant derivative that has been shown to inhibit Th17 differentiation. The purpose of this study was to examine the effect of halofuginone on CLAD development using a minor alloantigen‒mismatched mouse orthotopic lung transplant model. METHODS: C57BL/6 recipient mice received an orthotopic left lung transplant from C57BL/10 donors, mismatched for minor antigens...
April 2016: Journal of Heart and Lung Transplantation
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