Marzotto et al. showed that homeopathic preparations of Amica montana L. acted directly on gene expression of Tamm-Horsfall protein- 1 （THP-1） monocyte/macrophage cell lines activated with phorbol 12-mydstate 13- ac...Marzotto et al. showed that homeopathic preparations of Amica montana L. acted directly on gene expression of Tamm-Horsfall protein- 1 （THP-1） monocyte/macrophage cell lines activated with phorbol 12-mydstate 13- acetate and interleukin-4 （IL-4）. A. montana homeopathic dilutions are used in complementary and alternative medicine to treat inflammation disorders and post-traumatic events as well as for wound repair. The French Pharmacopoeia of these remedies uses 0.3% ethanol in each centesimal dilution. In this paper, we discuss how ethanol-containing A. montana homeopathic centesimal dilutions can change gene expression in IL-4- treated monocyte/macrophage THP-I. We assessed the role of ethanol in the Arnica homeopathic dilutions containing this alcohol by investigating its action on gene expression of THP-1 cell. Evidence would strongly suggest that the presence of ethanol in these remedies might play a fundamental role in the dilutions ability to affect gene expression, particularly for doses from 5c to 15c. Where, rather than playing a major role in the mesoscopic structure of water, the ethanol might have a chemical-physical role in the induction of THP-1 gene expression, apoptosis, and deoxyribonucleic acid function. This evidence generates a debate about the suggestion that the use of a binary-mixed solvent in homeopathic chemistry, used by Hahnemann since 1810, may be fundamental to explain the activity of homeopathy on cell models.展开更多
Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate cancer.It is involved in the release and polymerization of uro...Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate cancer.It is involved in the release and polymerization of uromodulin in the urine,which plays a role in kidney stone formation.In this work,we design new potential hepsin inhibitors for high activity,improved specificity towards hepsin,and promising ADMET properties.The ligands were developed in silico through a novel hierarchical pipeline.This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA(human hepatocyte growth factor activator).We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions.The ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental studies.The computational pipeline proposed is remarkably costefficient and can be easily adapted for designing inhibitors against new drug targets.展开更多
文摘Marzotto et al. showed that homeopathic preparations of Amica montana L. acted directly on gene expression of Tamm-Horsfall protein- 1 （THP-1） monocyte/macrophage cell lines activated with phorbol 12-mydstate 13- acetate and interleukin-4 （IL-4）. A. montana homeopathic dilutions are used in complementary and alternative medicine to treat inflammation disorders and post-traumatic events as well as for wound repair. The French Pharmacopoeia of these remedies uses 0.3% ethanol in each centesimal dilution. In this paper, we discuss how ethanol-containing A. montana homeopathic centesimal dilutions can change gene expression in IL-4- treated monocyte/macrophage THP-I. We assessed the role of ethanol in the Arnica homeopathic dilutions containing this alcohol by investigating its action on gene expression of THP-1 cell. Evidence would strongly suggest that the presence of ethanol in these remedies might play a fundamental role in the dilutions ability to affect gene expression, particularly for doses from 5c to 15c. Where, rather than playing a major role in the mesoscopic structure of water, the ethanol might have a chemical-physical role in the induction of THP-1 gene expression, apoptosis, and deoxyribonucleic acid function. This evidence generates a debate about the suggestion that the use of a binary-mixed solvent in homeopathic chemistry, used by Hahnemann since 1810, may be fundamental to explain the activity of homeopathy on cell models.
基金the Scottish Funding Councilthe University of Edinburgh
文摘Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate cancer.It is involved in the release and polymerization of uromodulin in the urine,which plays a role in kidney stone formation.In this work,we design new potential hepsin inhibitors for high activity,improved specificity towards hepsin,and promising ADMET properties.The ligands were developed in silico through a novel hierarchical pipeline.This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA(human hepatocyte growth factor activator).We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions.The ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental studies.The computational pipeline proposed is remarkably costefficient and can be easily adapted for designing inhibitors against new drug targets.
