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1.
Mol Omics ; 17(3): 376-393, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1281750

ABSTRACT

Metabolomics has emerged as an invaluable tool that can be used along with genomics, transcriptomics and proteomics to understand host-pathogen interactions at small-molecule levels. Metabolomics has been used to study a variety of infectious diseases and applications. The most common application of metabolomics is for prognostic and diagnostic purposes, specifically the screening of disease-specific biomarkers by either NMR-based or mass spectrometry-based metabolomics. In addition, metabolomics is of great significance for the discovery of druggable metabolic enzymes and/or metabolic regulators through the use of state-of-the-art flux analysis, for example, via the elucidation of metabolic mechanisms. This review discusses the application of metabolomics technologies to biomarker screening, the discovery of drug targets in infectious diseases such as viral, bacterial and parasite infections and immunometabolomics, highlights the challenges associated with accessing metabolite compartmentalization and discusses the available tools for determining local metabolite concentrations.


Subject(s)
Biomarkers/metabolism , Communicable Diseases/metabolism , Metabolomics/methods , Communicable Diseases/drug therapy , Drug Discovery , Humans , Metabolic Networks and Pathways/drug effects , Small Molecule Libraries/pharmacology , Small Molecule Libraries/therapeutic use
2.
Drug Deliv Transl Res ; 11(4): 1498-1508, 2021 08.
Article in English | MEDLINE | ID: covidwho-1237565

ABSTRACT

Transdermal drug delivery systems (TDDS) have many advantages and represent an excellent alternative to oral delivery and hypodermic injections. TDDS are more convenient and less invasive tools for disease and viral infection treatment, prevention, detection, and surveillance. The emerging development of microneedles for TDDS has facilitated improved skin barrier penetration for the delivery of macromolecules or hydrophilic drugs. Microneedle TDDS patches can be fabricated to deliver virus vaccines and potentially provide a viable alternative vaccine modality that offers improved immunogenicity, thermostability, simplicity, safety, and compliance as well as sharp-waste reduction, increased cost-effectiveness, and the capacity for self-administration, which could improve vaccine distribution. These advantages make TDDS-based vaccine delivery an especially well-suited option for treatment of widespread viral infectious diseases including pandemics. Because microneedle-based bioassays employ transdermal extraction of interstitial fluid or blood, they can be used as a minimally invasive approach for surveying disease markers and providing point-of-care (POC) diagnostics. For cutaneous viral infections, TDDS can provide localized treatment with high specificity and less systemic toxicity. In summary, TDDS, especially those that employ microneedles, possess special attributes that can be leveraged to reduce morbidity and mortality from viral infectious diseases. In this regard, they may have considerable positive impact as a modality for improving global health. In this article, we introduce the possible role and summarize the current literature regarding TDDS applications for fighting common cutaneous or systemic viral infectious diseases, including herpes simplex, varicella or herpes zoster, warts, influenza, measles, and COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Drug Delivery Systems/methods , Microinjections/methods , Administration, Cutaneous , Animals , Antiviral Agents/immunology , Antiviral Agents/metabolism , COVID-19/immunology , COVID-19/metabolism , Communicable Diseases/drug therapy , Communicable Diseases/immunology , Communicable Diseases/metabolism , Drug Delivery Systems/trends , Humans , Microinjections/trends
3.
Drug Deliv Transl Res ; 11(4): 1451-1455, 2021 08.
Article in English | MEDLINE | ID: covidwho-1217493

ABSTRACT

The importance of detection and treatments of infectious diseases has been stressed to the world by the ongoing COVID-19 pandemic. As a substitution of an external light source, self-luminescent therapeutics featuring in situ light emission aims to address the lack of tissue penetration in conventional photodynamic therapy (PDT). Luminol-based self-luminescent systems are successfully incorporated in PDT and detection of pathogens in infectious diseases. In these systems, luminol/hydrogen peroxide is served as luminescence source which can be activated by horseradish peroxidase (HRP). As a supplement strategy to the HRP-based bioluminescence, electrochemiluminescence (ECL) provided an electric-driven therapeutic solution and demonstrated potential capabilities of wearable healthcare devices with properly constructed transparent flexible hydrogels. Besides the diagnosis of infection and detection of bacteria, fungi and virus in solution or powder samples have been achieved by ATP-derived self-luminescence as the light source. In this inspirational note, we provide an overview on latest progress in the PDT and microbial detection by self-luminescent systems with an emphasis on the bioluminescence and ECL.


Subject(s)
Biosensing Techniques/methods , COVID-19/prevention & control , COVID-19/transmission , Luminescence , Photochemotherapy/methods , Animals , Biosensing Techniques/trends , COVID-19/metabolism , Communicable Diseases/metabolism , Communicable Diseases/transmission , Disease Transmission, Infectious/prevention & control , Humans , Photochemotherapy/trends
4.
Int J Mol Sci ; 22(5)2021 Mar 08.
Article in English | MEDLINE | ID: covidwho-1134168

ABSTRACT

The fruit fly, Drosophila melanogaster, has been used to understand fundamental principles of genetics and biology for over a century. Drosophila is now also considered an essential tool to study mechanisms underlying numerous human genetic diseases. In this review, we will discuss how flies can be used to deepen our knowledge of infectious disease mechanisms in vivo. Flies make effective and applicable models for studying host-pathogen interactions thanks to their highly conserved innate immune systems and cellular processes commonly hijacked by pathogens. Drosophila researchers also possess the most powerful, rapid, and versatile tools for genetic manipulation in multicellular organisms. This allows for robust experiments in which specific pathogenic proteins can be expressed either one at a time or in conjunction with each other to dissect the molecular functions of each virulent factor in a cell-type-specific manner. Well documented phenotypes allow large genetic and pharmacological screens to be performed with relative ease using huge collections of mutant and transgenic strains that are publicly available. These factors combine to make Drosophila a powerful tool for dissecting out host-pathogen interactions as well as a tool to better understand how we can treat infectious diseases that pose risks to public health, including COVID-19, caused by SARS-CoV-2.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/metabolism , Drosophila melanogaster/immunology , Drosophila melanogaster/metabolism , Animals , Communicable Diseases/microbiology , Communicable Diseases/virology , Drosophila melanogaster/microbiology , Drosophila melanogaster/virology , Host-Pathogen Interactions , Immunity, Innate , Signal Transduction , Virulence Factors/metabolism
5.
PLoS Pathog ; 17(1): e1009220, 2021 01.
Article in English | MEDLINE | ID: covidwho-1088772

ABSTRACT

The eponymous member of the interferon regulatory factor (IRF) family, IRF1, was originally identified as a nuclear factor that binds and activates the promoters of type I interferon genes. However, subsequent studies using genetic knockouts or RNAi-mediated depletion of IRF1 provide a much broader view, linking IRF1 to a wide range of functions in protection against invading pathogens. Conserved throughout vertebrate evolution, IRF1 has been shown in recent years to mediate constitutive as well as inducible host defenses against a variety of viruses. Fine-tuning of these ancient IRF1-mediated host defenses, and countering strategies by pathogens to disarm IRF1, play crucial roles in pathogenesis and determining the outcome of infection.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/therapy , Host-Pathogen Interactions/immunology , Immunity, Innate/immunology , Interferon Regulatory Factor-1/metabolism , Animals , Communicable Diseases/metabolism , Humans , Interferon Regulatory Factor-1/immunology
6.
Nutrients ; 13(1)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1067765

ABSTRACT

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.


Subject(s)
Aging/physiology , COVID-19/metabolism , Communicable Diseases/metabolism , Magnesium Deficiency/complications , Magnesium/metabolism , Aged , COVID-19/etiology , COVID-19/immunology , COVID-19/virology , Cation Transport Proteins/metabolism , Communicable Diseases/immunology , Communicable Diseases/microbiology , Communicable Diseases/virology , Epstein-Barr Virus Infections/metabolism , Female , Humans , Magnesium/immunology , Magnesium Deficiency/immunology , Magnesium Deficiency/metabolism , Male , SARS-CoV-2/immunology , X-Linked Combined Immunodeficiency Diseases/metabolism
7.
PLoS Pathog ; 17(2): e1009207, 2021 02.
Article in English | MEDLINE | ID: covidwho-1063225

ABSTRACT

The recent Coronavirus Disease 2019 pandemic has once again reminded us the importance of understanding infectious diseases. One important but understudied area in infectious disease research is the role of nuclear architecture or the physical arrangement of the genome in the nucleus in controlling gene regulation and pathogenicity. Recent advances in research methods, such as Genome-wide chromosome conformation capture using high-throughput sequencing (Hi-C), have allowed for easier analysis of nuclear architecture and chromosomal reorganization in both the infectious disease agents themselves as well as in their host cells. This review will discuss broadly on what is known about nuclear architecture in infectious disease, with an emphasis on chromosomal reorganization, and briefly discuss what steps are required next in the field.


Subject(s)
Cell Nucleus/genetics , Chromatin/metabolism , Communicable Diseases/genetics , Animals , COVID-19/genetics , COVID-19/metabolism , Cell Nucleus/metabolism , Chromatin/genetics , Chromosomes/genetics , Chromosomes/metabolism , Communicable Diseases/metabolism , Gene Expression Regulation , Humans
8.
Drug Deliv Transl Res ; 11(4): 1340-1351, 2021 08.
Article in English | MEDLINE | ID: covidwho-1047033

ABSTRACT

Infectious diseases, such as the coronavirus disease-19, SARS virus, Ebola virus, and AIDS, threaten the health of human beings globally. New viruses, drug-resistant bacteria, and fungi continue to challenge the human efficacious drug bank. Researchers have developed a variety of new antiviral and antibacterial drugs in response to the infectious disease crisis. Meanwhile, the development of functional materials has also improved therapeutic outcomes. As a natural material, chitosan possesses good biocompatibility, bioactivity, and biosafety. It has been proven that the cooperation between chitosan and traditional medicine greatly improves the ability of anti-infection. This review summarized the application and design considerations of chitosan-composed systems for the treatment of infectious diseases, looking forward to providing the idea of infectious disease therapy.


Subject(s)
Anti-Infective Agents/administration & dosage , Biocompatible Materials/administration & dosage , COVID-19/drug therapy , Chitosan/administration & dosage , Communicable Diseases/drug therapy , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/immunology , Anti-Bacterial Agents/pharmacokinetics , Anti-Infective Agents/immunology , Anti-Infective Agents/pharmacokinetics , Bandages/microbiology , Biocompatible Materials/pharmacokinetics , COVID-19/immunology , COVID-19/metabolism , Chitosan/immunology , Chitosan/pharmacokinetics , Communicable Diseases/immunology , Communicable Diseases/metabolism , Humans , Wound Healing/drug effects , Wound Healing/physiology
9.
Nutrients ; 13(1)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1016214

ABSTRACT

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.


Subject(s)
Aging/physiology , COVID-19/metabolism , Communicable Diseases/metabolism , Magnesium Deficiency/complications , Magnesium/metabolism , Aged , COVID-19/etiology , COVID-19/immunology , COVID-19/virology , Cation Transport Proteins/metabolism , Communicable Diseases/immunology , Communicable Diseases/microbiology , Communicable Diseases/virology , Epstein-Barr Virus Infections/metabolism , Female , Humans , Magnesium/immunology , Magnesium Deficiency/immunology , Magnesium Deficiency/metabolism , Male , SARS-CoV-2/immunology , X-Linked Combined Immunodeficiency Diseases/metabolism
10.
Semin Cell Dev Biol ; 115: 19-26, 2021 07.
Article in English | MEDLINE | ID: covidwho-1012549

ABSTRACT

The transition metal Cu is an essential micronutrient that serves as a co-factor for numerous enzymes involved in redox and oxygen chemistry. However, Cu is also a potentially toxic metal, especially to unicellular microbes that are in direct contact with their environment. Since 400 BCE, Cu toxicity has been leveraged for its antimicrobial properties and even today, Cu based materials are being explored as effective antimicrobials against human pathogens spanning bacteria, fungi, and viruses, including the SARS-CoV-2 agent of the 2019-2020 pandemic. Given that Cu has the double-edged property of being both highly toxic and an essential micronutrient, it plays an active and complicated role at the host-pathogen interface. Humans have evolved methods of incorporating Cu into innate and adaptive immune processes and both sides of the penny (Cu toxicity and Cu as a nutrient) are employed. Here we review the evolution of Cu in biology and its multi-faceted roles in infectious disease, from the viewpoints of the microbial pathogens as well as the animal hosts they infect.


Subject(s)
Anti-Bacterial Agents/pharmacology , COVID-19/drug therapy , Copper/metabolism , Host-Pathogen Interactions/drug effects , SARS-CoV-2/drug effects , Animals , COVID-19/virology , Communicable Diseases/drug therapy , Communicable Diseases/metabolism , Humans
11.
STAR Protoc ; 1(3): 100233, 2020 12 18.
Article in English | MEDLINE | ID: covidwho-978460

ABSTRACT

In December 2019, a new coronavirus, SARS-CoV-2, which causes the respiratory illness that led to the COVID-19 pandemic, was reported. In the face of such a new pathogen, special precautions must be taken to examine potentially infectious materials due to the lack of knowledge on disease transmissibility, infectivity, and molecular pathogenicity. Here, we present a complete and safe workflow for performing scRNA-seq experiments on blood samples of infected patients from cell isolation to data analysis using the micro-well based BD Rhapsody platform. For complete information on the use and execution of this protocol, please refer to Schulte-Schrepping et al. (2020).


Subject(s)
COVID-19 , Communicable Diseases , RNA-Seq/methods , Single-Cell Analysis/methods , Transcriptome/genetics , Biomarkers/blood , COVID-19/genetics , COVID-19/metabolism , Communicable Diseases/genetics , Communicable Diseases/metabolism , Humans , SARS-CoV-2 , Workflow
12.
Circ Arrhythm Electrophysiol ; 13(8): e008627, 2020 08.
Article in English | MEDLINE | ID: covidwho-641777

ABSTRACT

BACKGROUND: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K+ channel expression. METHODS: We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K+ channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time. RESULTS: In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K+ channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. CONCLUSIONS: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs. Graphic Abstract: A graphic abstract is available for this article.


Subject(s)
Communicable Diseases/metabolism , Cytokines/metabolism , Heart Arrest/metabolism , Heart Rate , Heart Ventricles/metabolism , Inflammation/metabolism , Leukocytes, Mononuclear/metabolism , Potassium Channels, Inwardly Rectifying/metabolism , Torsades de Pointes/metabolism , Action Potentials , Acute Disease , Adult , Aged , Aged, 80 and over , Anti-Infective Agents/adverse effects , Communicable Diseases/drug therapy , Communicable Diseases/epidemiology , Communicable Diseases/physiopathology , Female , Heart Arrest/epidemiology , Heart Arrest/physiopathology , Heart Rate/drug effects , Heart Ventricles/drug effects , Heart Ventricles/physiopathology , Humans , Inflammation/epidemiology , Inflammation/physiopathology , Leukocytes, Mononuclear/drug effects , Male , Middle Aged , Potassium Channels, Inwardly Rectifying/genetics , Prevalence , Risk Factors , Signal Transduction , Time Factors , Torsades de Pointes/epidemiology , Torsades de Pointes/physiopathology , Young Adult
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