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halofuginone

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https://www.readbyqxmd.com/read/29648988/coccidiostats-in-milk-development-of-a-multi-residue-method-and-transfer-of-salinomycin-and-lasalocid-from-contaminated-feed
#1
Konrad Pietruk, Małgorzata Olejnik, Andrzej Posyniak
A confirmatory multi-residue method was developed for the determination in milk of 19 coccidiostats (amprolium, arprinocid, clazuril, clopidol, decoquinate, diclazuril, ethopabate, halofuginone, lasalocid, maduramicin, monensin, narasin, nicarbazin, nequinate, robenidine, salinomycin, semduramicin, toltrazuril sulfone and toltrazuril sulfoxide). Sample preparation utilizing extraction with organic solvent and clean up by solid phase extraction and freezing was found reliable and time-efficient. Optimized chromatography and mass spectrometry conditions with positive and negative electrospray ionization achieved sufficient sensitivity and selectivity...
April 12, 2018: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/29621237/amino-acid-starvation-sensing-dampens-il-1%C3%AE-production-by-activating-riboclustering-and-autophagy
#2
Srikanth Battu, Sumbul Afroz, Jeevan Giddaluru, Saima Naz, Weishan Huang, Saratchandra Singh Khumukcham, Rafiq Ahmad Khan, SaleemYousuf Bhat, Insaf Ahmed Qureshi, Bramanandam Manavathi, Aleem Ahmed Khan, Avery August, Seyed Ehtesham Hasnain, Nooruddin Khan
Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)-dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes-such as stress granules (SGs)-via recruitment of RNA-binding proteins (RBPs) T cell-restricted intracellular antigen-1(TIA-1)/TIA-1-related (TIAR), which are further cleared through induction of autophagy...
April 5, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29559143/treatment-of-cryptosporidiosis-in-captive-green-iguanas-iguana-iguana
#3
Remigiusz Gałęcki, Rajmund Sokół
There are no standard guidelines for the treatment of cryptosporidiosis in reptiles. The aim of this study was to evaluate the efficacy of two cryptosporidiosis therapies in captive green iguanas. Eight green iguanas aged 2-6 years, including 6 (1 ♂ and 5 ♀) animals with chronic diarrhea, received treatment for cryptosporidiosis. The presence of Cryptosporidium sp. oocysts was determined in 8 iguanas (100%), Isospora sp. oocysts were detected in 3 animals (37.5%), and Oxyuridae eggs were observed in 5 iguanas (62...
March 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29524883/halofuginone-attenuates-intervertebral-discs-degeneration-by-suppressing-collagen-i-production-and-inactivating-tgf%C3%AE-and-nf-%C3%B0%C2%BAb-pathway
#4
Linghui Luo, Yong Gao, Cao Yang, Zengwu Shao, Xinghuo Wu, Shuai Li, Liming Xiong, Chao Chen
Most low back pain is caused by intervertebral discs (IVD) degeneration, a disease that prevalence is increasing with age. Halofuginone, an analog of ferbrifugine isolated from plant Dichroa febrifuga, has drawn much attention in recent years for the wide range of bioactivities in malaria, cancer, fibrotic and autoimmune diseases. In this study, we evaluated the benefit effects of halofuginone in IVD degeneration treatment in a validated rabbit puncture model. Halofuginone treatment could attenuate disc degeneration by suppressing the decrease of discs height and nucleus pulposus signal strength...
March 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29505748/neuronal-transforming-growth-factor-beta-signaling-via-smad3-contributes-to-pain-in-animal-models-of-chronic-pancreatitis
#5
Liansheng Liu, Yaohui Zhu, Michaël Noë, Qian Li, Pankaj Jay Pasricha
BACKGROUND & AIMS: Chronic pancreatitis (CP) is characterized by pancreatic inflammation and fibrosis, associated with increased pancreatic expression of transforming growth factor beta (TGFB). It is not clear how these might contribute to pain. We investigated whether TGFB signaling via SMAD induces sensitization of pancreatic sensory neurons to increase nociception. METHODS: CP was induced in Sprague-Dawley rats by infusion of trinitrobenzene sulfonic acid; some rats were given intrathecal infusions of TGFB1...
March 2, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29304439/cryptosporidium-outbreak-in-calves-on-a-large-dairy-farm-effect-of-treatment-and-the-association-with-the-inflammatory-response-and-short-term-weight-gain
#6
Tarmo Niine, Elisabeth Dorbek-Kolin, Brian Lassen, Toomas Orro
Cryptosporidium spp. infections in neonatal dairy calves can cause diarrhoea and, in rare cases, death. The infection is usually self-limiting, but halofuginone lactate (HL) can be used prophylactically. Calves (n=144) in the study were born during a 2-month period on one farm. A total of 901 serum and 767 faecal samples were collected. Based on HL treatment, the calves were divided into 3 groups: I) not treated, II) treated incorrectly (treatment started >48h after birth, or lasted <7days), and III) treated correctly (started <48h after birth, and lasted ≥7days)...
April 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29231257/halofuginone-induced-autophagy-suppresses-the-migration-and-invasion-of-mcf-7-cells-via-regulation-of-stmn1-and-p53
#7
Xiaojing Xia, Lei Wang, Xiaojian Zhang, Shan Wang, Lianchen Lei, Likun Cheng, Yanzhao Xu, Yawei Sun, Bolin Hang, Gaiping Zhang, YueYu Bai, JianHe Hu
Traditional Chinese medicines have been recognized as especially promising anticancer agents in modern anticancer research. Halofuginone (HF), an analog of quinazolinone alkaloid extracted from Dichroa febrifuga, is widely used in traditional medicine. However, whether HF inhibits the growth of breast cancer cells and/or reduces the migration and invasion of MCF-7 human breast cancer cells, as well as the underlying mechanisms in vitro, remains unclear. In this study, we report that an HF extract inhibits the growth of MCF-7 cells and reduces their migration and invasion, an important feature of potential anticancer agents...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29156807/halofuginone-inhibits-tgf-%C3%AE-bmp-signaling-and-in-combination-with-zoledronic-acid-enhances-inhibition-of-breast-cancer-bone-metastasis
#8
Patricia Juárez, Pierrick G J Fournier, Khalid S Mohammad, Ryan C McKenna, Holly W Davis, Xiang H Peng, Maria Niewolna, Alain Mauviel, John M Chirgwin, Theresa A Guise
More efficient therapies that target multiple molecular mechanisms are needed for the treatment of incurable bone metastases. Halofuginone is a plant alkaloid-derivative with antiangiogenic and antiproliferative effects. Here we demonstrate that halofuginone is an effective therapy for the treatment of bone metastases, through multiple actions that include inhibition of TGFβ and BMP-signaling. Halofuginone blocked TGF-β-signaling in MDA-MB-231 and PC3 cells showed by inhibition of TGF-β-induced Smad-reporter, phosphorylation of Smad-proteins, and expression of TGF-β-regulated metastatic genes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29066866/halofuginone-ameliorates-inflammation-in-severe-acute-hepatitis-b-virus-hbv-infected-sd-rats-through-ampk-activation
#9
Weili Zhan, Yanhong Kang, Ning Chen, Chongshan Mao, Yi Kang, Jia Shang
The hepatitis B virus (HBV) has caused acute and chronic liver diseases in ~350 million infected people worldwide. Halofuginone (HF) is a plant alkaloid which has been demonstrated to play a crucial role in immune regulation. Our present study explored the function of HF in the immune response of HBV-infected Sprague Dawley (SD) rats. Plasmid containing pCDNA3.1-HBV1.3 was injected in SD rats for the construction of an acute HBV-infected animal model. Our data showed that HF reduced the high concentrations of serum hepatitis B e-antigen, hepatitis B surface antigen, and HBV DNA induced by HBV infection...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29065190/discovery-and-pharmacological-characterization-of-a-new-class-of-prolyl-trna-synthetase-inhibitor-for-anti-fibrosis-therapy
#10
Akira Shibata, Masako Kuno, Ryutaro Adachi, Yosuke Sato, Harumi Hattori, Atsushi Matsuda, Yuumi Okuzono, Keiko Igaki, Yusuke Tominari, Terufumi Takagi, Masato Yabuki, Masanori Okaniwa
Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) is a well-known anti-fibrosis agent in preclinical and clinical studies which exerts its effect via inhibition of TGF-β/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds to the proline binding site of the catalytic domain of PRS. Here, we characterized a new class of PRS inhibitor (T-3833261) that is carefully designed in a way that binds to the ATP site of the catalytic domain and does not disrupt binding of proline...
2017: PloS One
https://www.readbyqxmd.com/read/28986385/the-role-of-halofuginone-in-fibrosis-more-to-be-explored
#11
REVIEW
Yin Luo, Xiaoyan Xie, Di Luo, Yuan Wang, Yijun Gao
Fibrosis, which can be defined as an abnormal or excessive accumulation of extracellular matrix (ECM), particularly fibrillar collagens, is a key driver of progressive organ dysfunction in many inflammatory and metabolic diseases, including idiopathic pulmonary fibrosis (IPF), cirrhosis, nephropathy, and oral submucous fibrosis (OSF). It has been estimated to contribute to ∼45% of deaths in the developed world. Therefore, agents that target specific fibrotic pathways, with the consequence of slowing, arresting, or even reversing the progression of tissue fibrogenesis, are urgently needed...
December 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28944864/halofuginone-attenuates-articular-cartilage-degeneration-by-inhibition-of-elevated-tgf%C3%A2-%C3%AE-1-signaling-in-articular-cartilage-in-a-rodent-osteoarthritis-model
#12
Wenbo Mu, Boyong Xu, Hairong Ma, Baochao Ji, Zhendong Zhang, Jiao Li, Abdusami Amat, Li Cao
Osteoarthritis (OA) is the most common degenerative condition of the weight‑bearing joints worldwide without effective medical therapy. In order to investigate whether administration of halofuginone (HF) may attenuate OA, the present study allocated 3‑month‑old male mice into Sham group, vehicle‑treated anterior cruciate ligament transection (ACLT) group and HF‑treated ACLT group. The present study determined that HF treatment reduced the expression of matrix metallopeptidase‑13 and collagen X in articular cartilage...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28822145/-advances-in-studies-on-autoimmune-diseases-treated-by-halofuginone
#13
REVIEW
Shi-Qi Wang, Ze-Hua Duan, Ya-Rong Zhao, Huan Dou
Halofuginone (HF) is a derivative of dichroine which is the extract of traditional Chinese medicine. It is widely used as an efficient anticoccidial drug. Recent studies have found that HF has unique biological activities, showing great potential capacities in the treatment of autoimmune diseases. In the article, we summarized the therapeutic effects of HF in a variety of autoimmune diseases and its mechanism, providing references for further clinical studies of HF.
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28713920/low%C3%A2-dose-halofuginone-inhibits-the-synthesis-of-type-i-collagen-without-influencing-type-ii-collagen-in-the-extracellular-matrix-of-chondrocytes
#14
Zeng Li, Hao Fei, Zhen Wang, Tianyi Zhu
Full‑thickness and large area defects of articular cartilage are unable to completely repair themselves and require surgical intervention, including microfracture, autologous or allogeneic osteochondral grafts, and autologous chondrocyte implantation. A large proportion of regenerative cartilage exists as fibrocartilage, which is unable to withstand impacts in the same way as native hyaline cartilage, owing to excess synthesis of type I collagen in the matrix. The present study demonstrated that low‑dose halofuginone (HF), a plant alkaloid isolated from Dichroa febrifuga, may inhibit the synthesis of type I collagen without influencing type II collagen in the extracellular matrix of chondrocytes...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28665346/a-novel-synthesis-of-the-efficient-anti-coccidial-drug-halofuginone-hydrobromide
#15
Junren Zhang, Qizheng Yao, Zuliang Liu
Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. Methods: First, 7-bromo-6-chloroquinazolin-4(3H)-one (2) was prepared from m-chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide (1) was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3H)-one (4) by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization...
June 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28501621/discovery-of-a-novel-prolyl-trna-synthetase-inhibitor-and-elucidation-of-its-binding-mode-to-the-atp-site-in-complex-with-l-proline
#16
Ryutaro Adachi, Kengo Okada, Robert Skene, Kazumasa Ogawa, Masanori Miwa, Kazuhiro Tsuchinaga, Shoichi Ohkubo, Tsutomu Henta, Tomohiro Kawamoto
Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family of enzymes and catalyzes the synthesis of prolyl-tRNAPro using ATP, l-proline, and tRNAPro as substrates. An ATP-dependent PRS inhibitor, halofuginone, was shown to suppress autoimmune responses, suggesting that the inhibition of PRS is a potential therapeutic approach for inflammatory diseases. Although a few PRS inhibitors have been derivatized from natural sources or substrate mimetics, small-molecule human PRS inhibitors have not been reported...
June 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28492544/halofuginone-dually-regulates-autophagic-flux-through-nutrient-sensing-pathways-in-colorectal-cancer
#17
Guo-Qing Chen, Rui-Hong Gong, Da-Jian Yang, Ge Zhang, Ai-Ping Lu, Siu-Cheong Yan, Shu-Hai Lin, Zhao-Xiang Bian
Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28487390/activation-of-the-amino-acid-response-pathway-blunts-the-effects-of-cardiac-stress
#18
Pu Qin, Pelin Arabacilar, Roberta E Bernard, Weike Bao, Alan R Olzinski, Yuanjun Guo, Hind Lal, Stephen H Eisennagel, Michael C Platchek, Wensheng Xie, Julius Del Rosario, Mohamad Nayal, Quinn Lu, Theresa Roethke, Christine G Schnackenberg, Fe Wright, Michael P Quaile, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Robert B Kirkpatrick, Xiaoyan A Qu, Deepak K Rajpal, Maria Faelth Savitski, Marcus Bantscheff, Gerard Joberty, Giovanna Bergamini, Thomas L Force, Gregory J Gatto, Erding Hu, Robert N Willette
BACKGROUND: The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure...
May 9, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28440200/effect-of-halofuginone-on-the-pathogenesis-of-autoimmune-thyroid-disease-in-different-mice-models
#19
Xin Hou, Jin Zhou, Rong Yang, Shanshan Liu, Mei Bi, Tong Liu, Chenling Fan, Haixia Guan, Yushu Li, Zhongyan Shan, Weiping Teng
OBJECTIVE: Our objectives were to investigate the therapeutic effect of halofuginone (HF) in the treatment of autoimmune thyroid diseases (AITDs) and explore its underlying mechanism of action. METHODS: The Graves&#039; disease (GD) model was generated by immunizing female BALB/c mice with adenovirus expressing the TSH receptor A subunit (Ad-TSHR289). The Ad-TSHRA+HF and Ad-TSHRA+DMSO groups were injected intraperitoneally with HF or the vehicle control (DMSO), respectively...
April 23, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28339722/prevalence-and-drug-resistance-of-avian-eimeria-species-in-broiler-chicken-farms-of-zhejiang-province-china
#20
L-H Lan, B-B Sun, B-X-Z Zuo, X-Q Chen, A-F Du
In this study, coccidia were isolated and identified from 5 main poultry farms located in Zhejiang province, eastern China. The overall prevalence of Eimeria spp. was 30.7% (95 of 310). Five common species were observed: E. tenella, E. acervulina, E. maxima, E. necatrix, and E. mitis. Two isolates (HZ and QZ) were tested for sensitivity to 8 anticoccidial drugs using 4 indexes including anticoccidial index (ACI), percent of optimum anticoccidial activity (POAA), reduction of lesion scores (RLS), and relative oocyst production (ROP): sulfachloropyrazine, toltrazuril, diclazuril, sulfamonomethoxine/trimethoprim, and amprolium; sulfaquinoxaline/sulfadimethoxine, nicarbazin, and halofuginone...
July 1, 2017: Poultry Science
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