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Metabolites
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Metabolomic Approaches to Dissecting the Molecular Mechanisms Driving Pharmacologic Responses
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Metabolomic Approaches to Dissecting the Molecular Mechanisms Driving Pharmacologic Responses

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Pharmacology and Drug Metabolism".

Deadline for manuscript submissions: closed (15 October 2021) | Viewed by 6658

Special Issue Editors

Prof. Dr. Stan Gee Louie

E-Mail Website
Guest Editor
Department of Clinical Pharmacy, University of Southern California, Los Angeles, CA 90007, USA
Interests: drug development along with the tissue reparative and inflammatory pathways found in the renin angiotensin/aldosterone system and bioactive lipid pathways
Dr. Isaac Asante

E-Mail Website
Assistant Guest Editor
School of Pharmacy, University of Southern California, Los Angeles, CA 90007, USA
Interests: development of therapeutic interventions and biomarkers using metabolomic approaches

Special Issue Information

Dear Colleagues,

The sequencing of the human genome has ushered in the age of “omics”. The vast amount of information has accelerated our understanding as to how subtle changes in biology may determine wellness or disease. Metabolomics is able to phenotype the various changes in a system and thus allow investigators to not only profile the changes but also identify targets and strategies for therapeutics. Metabolomics is a highly precise tool that can also be used to verify the biological effects of the new chemical or biological entities.

This Special Issue of Metabolites will address the evolving technology and analysis of metabolomics and lipidomics investigation. We will highlight how metabolomics is evolving in disease monitoring and drug development. Our ability to comprehensively understand the impact of various treatments will give us confidence as to how a drug may work. In addition, it may also enable us to identify potential risks associated with the treatments. All of these will ensure the development of more effective therapies and the optimization of safety margins. We encourage colleagues to submit manuscripts dealing with how metabolite profiling can help us to interrogate molecular mechanisms in vitro, in vivo, and in the clinic. We also encourage colleagues to share their experiences with the use of metabolomics for monitoring drug effects in humans with the scientific community.

Prof. Dr. Stan Gee Louie
Dr. Isaac Asante
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolomics in drug discovery
  • precision medicine
  • LCMS methods
  • pharmacologic responses
  • metabolite identification and quantification
  • bioanalyses of metabolites
  • machine learning

Published Papers (2 papers)

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Research

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11 pages, 625 KiB  
Article
Alterations in Renin–Angiotensin System (RAS) Peptide Levels in Patients with HIV
by Isaac Asante, Angela Lu, Brooks I. Mitchell, William A. Boisvert, Cecilia M. Shikuma, Dominic C. Chow and Stan G. Louie
Metabolites 2023, 13(1), 61; https://doi.org/10.3390/metabo13010061 - 31 Dec 2022
Viewed by 1787
Abstract
Chronic HIV infection has long been associated with an increased risk for cardiovascular diseases. The metabolites of the renin–angiotensin system (RAS) such as angiotensin II (AngII) play an important role in regulating blood pressure and fluid dynamics. Cross-sectional analysis of HIV-positive individuals ( [...] Read more.
Chronic HIV infection has long been associated with an increased risk for cardiovascular diseases. The metabolites of the renin–angiotensin system (RAS) such as angiotensin II (AngII) play an important role in regulating blood pressure and fluid dynamics. Cross-sectional analysis of HIV-positive individuals (n = 71, age > 40 years, stable ART > 3 months with HIV viral load < 50 copies/mL) were compared to a similar HIV seronegative group (n = 72). High-resolution B-mode ultrasound images of the right carotid bifurcation (RBIF) and right common carotid artery (RCCA) were conducted to measure the extent of carotid atherosclerotic vascular disease. Plasma RAS peptide levels were quantified using a liquid chromatography-mass spectrometry-based metabolomics assay. RAS peptide concentrations were compared between persons with HIV and persons without HIV, correlating their association with clinical and cardiac measures. Median precursor peptides (Ang(1-12) and AngI) were significantly higher in the HIV-positive group compared to the HIV-negative. Analyses of the patient subgroup not on antihypertensive medication revealed circulating levels of AngII to be four-fold higher in the HIV-positive subgroup. AngII and TNF-alpha levels were found to have a positive association with RCCA, and AngI/Ang(1-12) ratio and TNF-alpha levels were found to have a positive association with RBIF. In both predictive models, AngIII had a negative association with either RCCA or RBIF, which may be attributed to its ability to bind onto AT2R and thus oppose pro-inflammatory events. These results reveal systemic alterations in RAS as a result of chronic HIV infection, which may lead to the activation of inflammatory pathways associated with carotid thickening. RAS peptide levels and cytokine markers were associated with RCCA and RBIF measurements. Full article
(This article belongs to the Special Issue Metabolomic Approaches to Dissecting the Molecular Mechanisms Driving Pharmacologic Responses)
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Review

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33 pages, 928 KiB  
Review
Lipidomics in Understanding Pathophysiology and Pharmacologic Effects in Inflammatory Diseases: Considerations for Drug Development
by Kabir Ahluwalia, Brandon Ebright, Kingsley Chow, Priyal Dave, Andrew Mead, Roy Poblete, Stan G. Louie and Isaac Asante
Metabolites 2022, 12(4), 333; https://doi.org/10.3390/metabo12040333 - 07 Apr 2022
Cited by 13 | Viewed by 4450
Abstract
The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific [...] Read more.
The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific lipids and quantify their levels. Simultaneous quantification of a set of lipids can be achieved using high sensitivity mass spectrometry (MS) techniques, whose technological advancements have significantly improved over the last decade. This has unlocked the power of metabolomics/lipidomics allowing the dynamic characterization of metabolic systems. Lipidomics is a subset of metabolomics for multianalyte identification and quantification of endogenous lipids and their metabolites. Lipidomics-based technology has the potential to drive novel biomarker discovery and therapeutic development programs; however, appropriate standards have not been established for the field. Standardization would improve lipidomic analyses and accelerate the development of innovative therapies. This review aims to summarize considerations for lipidomic study designs including instrumentation, sample stabilization, data validation, and data analysis. In addition, this review highlights how lipidomics can be applied to biomarker discovery and drug mechanism dissection in various inflammatory diseases including cardiovascular disease, neurodegeneration, lung disease, and autoimmune disease. Full article
(This article belongs to the Special Issue Metabolomic Approaches to Dissecting the Molecular Mechanisms Driving Pharmacologic Responses)
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