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https://www.readbyqxmd.com/read/29127220/therapeutic-potential-of-micrornas-for-the-treatment-of-renal-fibrosis-and-ckd
#1
Wenshan Lv, Fan Fan, Yangang Wang, Ezekiel Gonzalez-Fernandez, Chen Wang, Lili Yang, George W Booz, Richard J Roman
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29110790/long-term-management-of-patients-with-end-stage-lung-diseases
#2
REVIEW
Domenica Federica Briganti, Frank D'Ovidio
Long-term management of end-stage lung disease differs from interstitial lung disease to chronic obstructive pulmonary disease to cystic fibrosis to pulmonary vascular disease. The management includes pharmacological therapy that is disease specific such as antibiotic therapy for cystic fibrosis, antifibrotic drugs in idiopathic pulmonary fibrosis; long-acting beta-agonists, long-acting muscarinic antagonist, and inhaled corticosteroids in chronic obstructive pulmonary disease; and vasodilators in pulmonary arterial hypertension...
June 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/29109865/om-101-decreases-the-fibrotic-response-associated-with-proliferative-vitreoretinopathy
#3
Zeev Dvashi, Keren Ben-Yaakov, Tamir Weinberg, Yoel Greenwald, Ayala Pollack
Purpose: This study aimed to investigate the effect of OM-101 on the fibrotic response occurring in proliferative vitreoretinopathy (PVR) in an animal model. Methods: Antifibrotic effect of OM-101 was investigated in vivo. As control, eight weeks old c57black mice underwent intravitreal injection with Hepes (group A) or dispase (0.3 units), to induce retinal detachment (RD) and PVR. The dispase-injected mice were randomly divided into two groups B and C (N = 25 mice); in group C, the eyes were treated with intravitreal injection of OM-101 (3 μl), and group B with PBS, as a control...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29109128/sox9-predicts-progression-toward-cirrhosis-in-patients-while-its-loss-protects-against-liver-fibrosis
#4
Varinder S Athwal, James Pritchett, Jessica Llewellyn, Katherine Martin, Elizabeth Camacho, Sayyid Ma Raza, Alexander Phythian-Adams, Lindsay J Birchall, Aoibheann F Mullan, Kim Su, Laurence Pearmain, Grace Dolman, Abed M Zaitoun, Scott L Friedman, Andrew MacDonald, William L Irving, Indra N Guha, Neil A Hanley, Karen Piper Hanley
Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study, we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression toward cirrhosis...
November 6, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29067666/test-of-antifibrotic-drugs-in-a-cellular-model-of-fibrosis-based-on-muscle-derived-fibroblasts-from-duchenne-muscular-dystrophy-patients
#5
Simona Zanotti, Marina Mora
An in vitro model of muscle fibrosis, based on the use of primary human fibroblasts isolated from muscle biopsies of patients affected by Duchenne muscular dystrophies (DMD) and cultivated in monolayer and 3D conditions, is used to test the potential antifibrotic activity of pirfenidone (PFD). This in vitro model may be usefully also to evaluate the toxicity and efficacy of other candidate molecules for the treatment of fibrosis. The drug toxicity is evaluated using a colorimetric assay based on the conversion of tetrazolium salt (MTT) to insoluble formazan, while the effect of the drug on cell proliferation is measured with the bromodeoxyuridine incorporation assay...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29050313/adipose-derived-mesenchymal-stem-cells-employed-exosomes-to-attenuate-aki-ckd-transition-through-tubular-epithelial-cell-dependent-sox9-activation
#6
Fengming Zhu, Octavia L S Chong Lee Shin, Guangchang Pei, Zhizhi Hu, Juan Yang, Han Zhu, Meng Wang, Jingyi Mou, Jie Sun, Yuxi Wang, Qian Yang, Zhi Zhao, Huzi Xu, Hui Gao, Weiqi Yao, Xiao Luo, Wenhui Liao, Gang Xu, Rui Zeng, Ying Yao
Acute kidney injury (AKI) predisposes patients to an increased risk into progressive chronic kidney disease (CKD), however effective treatments are still elusive. This study aimed to investigate the therapeutic efficacy of human adipose-derived MSCs (hAD-MSCs) in the prevention of AKI-CKD transition, and illuminate the role of Sox9, a vital transcription factor in the development of kidney, in this process. C57BL/6 mice were subjected to unilateral renal ischemia/reperfusion (I/R) with or without hAD-MSC treatment...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049722/a-ppar-gamma-agonist-rosiglitazone-suppresses-fibrotic-response-in-human-pterygium-fibroblasts-by-modulating-the-p38-mapk-pathway
#7
Selikem Abla Nuwormegbe, Joon Hyung Sohn, Sun Woong Kim
Purpose: Fibroblast activation may play an important role in pterygium progression. Synthetic peroxisome proliferator-activated receptor γ (PPAR-γ) ligands have been shown to be effective antifibrotic agents against transforming growth factor β1 (TGF-β1) induced fibrosis in several tissues. We aimed to investigate the antifibrotic effects of the PPAR-γ ligand rosiglitazone in pterygium fibroblasts and the underlying mechanisms. Methods: Profibrotic activation was induced by TGF-β1 in primary cultured human pterygium fibroblasts and the effect of rosiglitazone treatment on α-smooth muscle actin (α-SMA), and extra cellular matrix proteins synthesis was detected by western blotting, real-time PCR, immunostaining, and flow cytometry...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28987945/simvastatin-exerts-antifibrotic-effect-and-potentiates-the-antischistosomal-effects-of-praziquantel-in-a-murine-model-role-of-il10
#8
Ahlam Elmasry, Nabil M Aladeeb, Amro Elkaref, Nora Aboulfotouh
Previous studies on simvastatin use in experimental schistosomiasis in mice did not provide a full explanation of its mechanism as antischisome. In this study, we tried to find out the role of IL-10 in the mechanism of action of simvastatin. We used 50 clear mice. Ten were used as normal not treated while 40 were infected with shistosome mansoni then divided into 4 groups; 3 treated groups by praziquantel, simvastatin and combined (praziquantel plus simvastatin) respectively and one group non-treated. The simvastatin treated group showed shortening and loss of the tubercles and disappearance of the spines with swelling and twisted shape of the worms...
October 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28974541/when-to-start-and-when-to-stop-antifibrotic-therapies
#9
REVIEW
Sebastiano Emanuele Torrisi, Mauro Pavone, Ada Vancheri, Carlo Vancheri
Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure and death. Today, for the first time, two drugs that may reduce the inexorable progression of the disease are available, suggesting that treatment with specific drugs for IPF should be started as soon as diagnosis is made. This applies to any disease and particularly to IPF, which is marked by a 5-year survival comparable or even worse than many cancers...
September 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28947028/serum-surfactant-protein-d-predicts-the-outcome-of-patients-with-idiopathic-pulmonary-fibrosis-treated-with-pirfenidone
#10
Kimiyuki Ikeda, Masanori Shiratori, Hirofumi Chiba, Hirotaka Nishikiori, Keiki Yokoo, Atsushi Saito, Yoshihiro Hasegawa, Koji Kuronuma, Mitsuo Otsuka, Gen Yamada, Hiroki Takahashi
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone...
October 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28942086/validation-of-a-52-gene-risk-profile-for-outcome-prediction-in-patients-with-idiopathic-pulmonary-fibrosis-an-international-multicentre-cohort-study
#11
Jose D Herazo-Maya, Jiehuan Sun, Philip L Molyneaux, Qin Li, Julian A Villalba, Argyrios Tzouvelekis, Heather Lynn, Brenda M Juan-Guardela, Cristobal Risquez, Juan C Osorio, Xiting Yan, George Michel, Nachelle Aurelien, Kathleen O Lindell, Melinda J Klesen, Miriam F Moffatt, William O Cookson, Yingze Zhang, Joe G N Garcia, Imre Noth, Antje Prasse, Ziv Bar-Joseph, Kevin F Gibson, Hongyu Zhao, Erica L Herzog, Ivan O Rosas, Toby M Maher, Naftali Kaminski
BACKGROUND: The clinical course of idiopathic pulmonary fibrosis (IPF) is unpredictable. Clinical prediction tools are not accurate enough to predict disease outcomes. METHODS: We enrolled patients with IPF diagnosis in a six-cohort study at Yale University (New Haven, CT, USA), Imperial College London (London, UK), University of Chicago (Chicago, IL, USA), University of Pittsburgh (Pittsburgh, PA, USA), University of Freiburg (Freiburg im Breisgau, Germany), and Brigham and Women's Hospital-Harvard Medical School (Boston, MA, USA)...
November 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28940685/antifibrotic-effects-of-pentoxifylline-improve-the-efficacy-of-gemcitabine-in-human-pancreatic-tumor-xenografts
#12
Jung Ho Kim, Byung Cheol Shin, Won Sang Park, Jaehwi Lee, Hyo-Jeong Kuh
We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. PTX given for 2 weeks prior to giving DOX improved drug distribution by 1...
September 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28932114/spermidine-mediated-poly-lactic-co-glycolic-acid-nanoparticles-containing-fluorofenidone-for-the-treatment-of-idiopathic-pulmonary-fibrosis
#13
Jing Tang, Jianming Li, Guo Li, Haitao Zhang, Ling Wang, Dai Li, Jinsong Ding
Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic-co-glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28915874/unmet-needs-in-the-treatment-of-idiopathic-pulmonary-fibrosis-insights-from-patient-chart-review-in-five-european-countries
#14
Toby M Maher, Maria Molina-Molina, Anne-Marie Russell, Francesco Bonella, Stéphane Jouneau, Elena Ripamonti, Judit Axmann, Carlo Vancheri
BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. METHODS: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care...
September 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28912805/antifibrotic-effect-of-lactulose-on-a-methotrexate-induced-liver-injury-model
#15
Banu Taskin, Mümin Alper Erdoğan, Gürkan Yiğittürk, Damla Günenç, Oytun Erbaş
The most severe side effect of prolonged MTX treatment is hepatotoxicity. The aim of this study is to investigate the effect of lactulose treatment on MTX-induced hepatotoxicity in a rat model. Twenty-four male rats were included in the study. Sixteen rats were given a single dose of 20 mg/kg MTX to induce liver injury. Eight rats were given no drugs. 16 MTX-given rats were divided into two equal groups. Group 1 subjects were given lactulose 5 g/kg/day, and group 2 subjects were given saline 1 ml/kg/day for 10 days...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28911022/hypertensive-cardiovascular-risk-pulsatile-hemodynamics-gender-and-therapeutic-implications
#16
Michel E Safar, Harold Smulyan
PURPOSE: In recent years, the predictive value of 2 pulsatile parameters has been extensively studied in hypertension: aortic stiffness and pulse pressure (PP) amplification. Aortic stiffness is an index of aortic rigidity and PP-amplification is the ratio between central and brachial PP, an indirect evaluation of wave reflections. Both are safe, independent, noninvasive predictors of overall and cardiovascular risk. Our purpose is to determine the validity of these parameters in 2 different circumstances: gender and therapeutic implications...
October 1, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28898237/nintedanib-selectively-inhibits-the-activation-and-tumour-promoting-effects-of-fibroblasts-from-lung-adenocarcinoma-patients
#17
M Gabasa, R Ikemori, F Hilberg, N Reguart, J Alcaraz
BACKGROUND: Nintedanib is a clinically approved multikinase receptor inhibitor to treat non-small cell lung cancer with adenocarcinoma (ADC) histology in combination with docetaxel, based on the clinical benefits reported on ADC but not on squamous cell carcinoma (SCC), which are the two most common histologic lung cancer subtypes. METHODS: We examined the potential role of tumour-associated fibroblasts (TAFs) in the differential effects of nintedanib in ADC and SCC...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28893365/coffee-consumption-and-prevention-of-cirrhosis-in-support-of-the-caffeine-hypothesis
#18
Jonathan Dranoff
It is widely acknowledged that coffee is the most widely used drug on Earth. While this is true, coffee is also a foodstuff with wide variation, so its use is often directed at satisfying dietary urges. When used as a drug, coffee is almost invariably used as a stimulant rather than to treat or prevent particular diseases. Thus, it has been an exciting revelation in recent years that coffee consumption is inversely related to progression of liver fibrosis to cirrhosis and even hepatocellular carcinoma.As is often the case, epidemiological observations have preceded pathophysiological explanations for this effect...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28890106/development-of-a-peptide-modified-sirna-nanocomplex-for-hepatic-stellate-cells
#19
Zhen Zhao, Yuanke Li, Akshay Jain, Zhijin Chen, Hao Liu, Wei Jin, Kun Cheng
Insulin-like growth factor 2 receptor (IGF2R) is overexpressed in activated hepatic stellate cells (HSCs) and therefore can be utilized for HSC-specific drug delivery. We recently discovered an IGF2R-specific peptide using a novel biopanning. Here, we adopted biotin-conjugated IGF2R-specific peptide, cholesterol, and vitamin A as the targeting ligands for the neutravidin-based siRNA nanocomplex to deliver PCBP2 siRNA, a potentially antifibrotic agent, to HSCs. Compared to vitamin A and cholesterol, the IGF2R-specific peptide exhibited the highest targeting effect to human LX-2 HSC, rat HSC-T6 cell line, and activated primary rat HSCs...
September 7, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28880053/liver-fibrosis-the-2017-state-of-art
#20
Gian P Caviglia, Chiara Rosso, Sharmila Fagoonee, Giorgio M Saracco, Rinaldo Pellicano
Liver fibrosis is a wound-healing response to a wide spectrum of chronic liver injuries. It is characterized by loss of hepatocytes and alteration in hepatic architecture following an imbalance between extracellular matrix synthesis and degradation. Irrespectively of underlying etiology, fibrosis may progress to cirrhosis and specific pathogenetic mechanisms as well as different disease patterns may be identified according to etiology. Liver biopsy is still considered the gold standard for fibrosis assessment, despite the fact that it is invasive, has poor patient compliance and is not exempt of complications...
September 5, 2017: Panminerva Medica
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