scholarly journals Current Biomedical Use of Copper Chelation Therapy

2020 ◽  
Vol 21 (3) ◽  
pp. 1069 ◽  
Author(s):  
Silvia Baldari ◽  
Giuliana Di Rocco ◽  
Gabriele Toietta
Keyword(s):  
Clinical Trials ◽  
Idiopathic Pulmonary Fibrosis ◽  
Genetic Disease ◽  
Copper Concentration ◽  
Chelating Agents ◽  
Chelation Therapy ◽  
Biological Processes ◽  
Copper Chelation ◽  
Excess Copper ◽  
Parkinson’S Diseases

Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

scholarly journals Incorporating radiomics into clinical trials: expert consensus on considerations for data-driven compared to biologically driven quantitative biomarkers

2021 ◽  
Author(s):  
Laure Fournier ◽  
Lena Costaridou ◽  
Luc Bidaut ◽  
Nicolas Michoux ◽  
Frederic E. Lecouvet ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Quantitative Imaging ◽  
A Priori ◽  
External Validation ◽  
Data Driven ◽  
Imaging Biomarkers ◽  
Clinical Validation ◽  
Biological Processes ◽  
Imaging Data ◽  
Selection Of

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

scholarly journals Identification of Key Candidate Genes Involved in the Progression of Idiopathic Pulmonary Fibrosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1123
Author(s):  
Yu Cui ◽  
Jie Ji ◽  
Jiwei Hou ◽  
Yi Tan ◽  
Xiaodong Han
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Candidate Genes ◽  
Expression Profiles ◽  
Biological Processes ◽  
Protein Protein Interaction ◽  
Novel Treatments ◽  
Kegg Pathway Analysis ◽  
Cell Components ◽  
Upregulated Genes

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein–protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.

scholarly journals Genetic overlap between idiopathic pulmonary fibrosis and COVID−19

2021 ◽  
Author(s):  
Richard J Allen ◽  
Beatriz Guillen-Guio ◽  
Emma Croot ◽  
Luke M Kraven ◽  
Samuel Moss ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Biological Processes ◽  
Genetic Loci ◽  
Genome Wide ◽  
Genetic Overlap ◽  
Causal Variants ◽  
Shared Genetic

AbstractGenome-wide association studies (GWAS) of coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) have identified genetic loci associated with both traits, suggesting possible shared biological mechanisms. Using updated GWAS of COVID-19 and IPF, we evaluated the genetic overlap between these two diseases and identified four genetic loci (including one novel) with likely shared causal variants between severe COVID-19 and IPF. Although there was a positive genetic correlation between COVID-19 and IPF, two of these four shared genetic loci had an opposite direction of effect. IPF-associated genetic variants related to telomere dysfunction and spindle assembly showed no association with COVID-19 phenotypes. Together, these results suggest there are both shared and distinct biological processes driving IPF and severe COVID-19 phenotypes.

Glycosyl-Curcuminoids as Potential New Chelating Agents in Iron Overload Chelation Therapy

2004 ◽  
Vol 2004 (3) ◽  
pp. 646-652 ◽  
Author(s):  
Beatrice Arezzini ◽  
Marco Ferrali ◽  
Erika Ferrari ◽  
Romano Grandi ◽  
Stefano Monti ◽  
...  
Keyword(s):  
Iron Overload ◽  
Chelating Agents ◽  
Chelation Therapy

scholarly journals Standardization of the 6-min walk test in clinical trials of idiopathic pulmonary fibrosis

2021 ◽  
Vol 100 ◽  
pp. 106227
Author(s):  
Lisa Lancaster ◽  
Ann Fieuw ◽  
Joyce Meulemans ◽  
Paul Ford ◽  
Steven D. Nathan
Keyword(s):  
Clinical Trials ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Walk Test

scholarly journals Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs

2020 ◽  
Vol 21 (2) ◽  
pp. 524 ◽  
Author(s):  
Marina R. Hadjicharalambous ◽  
Mark A. Lindsay
Keyword(s):  
Chronic Disease ◽  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Lung Fibroblast ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Non Coding Rnas

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as the secretion of fibrotic and inflammatory mediators, have been strongly associated with the development and progression of IPF. Significantly, long non-coding RNAs (lncRNAs) are emerging as modulators of multiple biological processes, although their function and mechanism of action in IPF is poorly understood. LncRNAs have been shown to be important regulators of several diseases and their aberrant expression has been linked to the pathophysiology of fibrosis including IPF. This review will provide an overview of this emerging role of lncRNAs in the development of IPF.

scholarly journals Current clinical trials for the treatment of idiopathic pulmonary fibrosis

Respirology ◽  
2010 ◽  
Vol 15 (1) ◽  
pp. 19-31 ◽  
Author(s):  
Ross C. KLINGSBERG ◽  
Steven E. MUTSAERS ◽  
Joseph A. LASKY
Keyword(s):  
Clinical Trials ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis
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