Genetic Mechanisms of Asthma and the Implications for Drug Repositioning

Huo, Yue; Zhang, Hongyu

doi:10.3390/genes9050237

Cited by 19 publications

(18 citation statements)

References 129 publications

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“…For juvenile-onset asthma, symptoms are similar to adults but there is more emphasis on family history and total serum IgE levels to aid diagnosis [51]. As current diagnostic technology is thought to be sufficient to catch new cases, translational medicine is currently focused on genomic screening to predict prevalence and treatment responses [52,53].…”

Section: Diagnosticsmentioning

confidence: 99%

Biologic Treatments for Asthma and Chronic Obstructive Pulmonary Disorder

Kusumoto

Mathis

2021

Allergies

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The global COVID-19 pandemic has brought respiratory disease to the forefront of public health, but asthma prevalence has been rising globally for decades. Asthma is mediated by errant immune activation and airway remodeling, but the influences of environment, nutrition, and comorbidities (e.g., asthma-chronic obstructive pulmonary disorder-overlap [ACO]) are still poorly understood. Even as a new generation of biologic-based treatments offer better airway control and reductions in mortality, a lack of prophylactic treatments and mechanistic understanding complicates efforts to prevent pathogenesis. This review will explicate and synthesize current knowledge on the effect of ACO and biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) on pathogenesis, treatment, and prognosis.

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Section: Diagnosticsmentioning

confidence: 99%

Biologic Treatments for Asthma and Chronic Obstructive Pulmonary Disorder

Kusumoto

Mathis

2021

Allergies

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“…Some of the changes include alterations to inflammatory, smooth muscle contractility and epithelial barrier integrity genes. Some of the genes for example IL-4 receptor and ADAM metallopeptidase domain 33 (ADAM33) have been linked to asthma [ 8 ]. These genes have steadily shown similar link to asthma phenotypes in diversified populations and are therefore purported to contribute mainly to the pathogenesis of asthma [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma

et al. 2021

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Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.

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“…This occurs because repositioning candidates have often been through several stages of development, including efficacy, pharmacokinetics, pharmacodynamics and toxicity, and may even be marketed entities (Figure 1). The repurposing of drugs has been applied in several chemotherapeutic strategies to treat human health disorders such as cancer (Antoszczak et al, 2020;Armando et al, 2020;Masuda et al, 2020;Mudduluru et al, 2016;Nowak-Sliwinska et al, 2019;Serafin et al, 2019), neurodegenerative diseases (Corbett et al, 2015;De Castro et al, 2018), neglected tropical diseases (Andrade et al, 2019;Sbaraglini et al 2016), autoimmune diseases (Grammer and Lipsky, 2017), asthma (Huo and Zhang, 2018), psoriasis (Xu and Zhang, 2017), cystic fibrosis (Valeria et al;, and systemic lupus erythematosus (Grammer et al, 2016), to mention a few. With the development of computational methods and the increasing availability of novel types of big data (Kwon et al, 2019), the major limitation to find a new indication of a known drug lays in the identification of the molecular target of the disease of interest.…”

Section: Introductionmentioning

confidence: 99%

Repurposing old drugs to fight multidrug resistant cancers

Dinić

Efferth

García-Sosa

et al. 2020

Drug Resistance Updates

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Overcoming multidrug resistance represents a major challenge for cancer treatment.In the search for new chemotherapeutics to treat malignant diseases, drug repurposing gained a tremendous interest during the past years. Repositioning candidates have often emerged through several stages of clinical drug development, and may even be marketed, thus attracting the attention and interest of pharmaceutical companies as well as regulatory agencies. Typically, drug repositioning has been serendipitous, using undesired side effects of small molecule drugs to exploit new disease indications. As bioinformatics gain increasing popularity as an integral component of drug discovery, more rational approaches are needed. Herein, we show some practical examples of in silico approaches such as pharmacophore modelling, as well as pharmacophore-and docking-based virtual screening for a fast and cost-effective repurposing of small molecule drugs against multidrug resistant cancers. We provide a timely and comprehensive overview of compounds with considerable potential to be repositioned for cancer therapeutics. These drugs are from diverse chemotherapeutic classes. We emphasize the scope and limitations of anthelmintics, antibiotics, antifungals, antivirals, antimalarials, antihypertensives, psychopharmaceuticals and antidiabetics that have shown extensive immunomodulatory, antiproliferative, proapoptotic, and antimetastatic potential. These drugs, either used alone or in combination with existing anticancer chemotherapeutics, represent strong candidates to prevent or overcome drug resistance. We particularly focus on outcomes and future perspectives of drug repositioning for the treatment of multidrug resistant tumors and discuss current possibilities and limitations of preclinical and clinical investigations.

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Genetic Mechanisms of Asthma and the Implications for Drug Repositioning

Cited by 19 publications

References 129 publications

Biologic Treatments for Asthma and Chronic Obstructive Pulmonary Disorder

Biologic Treatments for Asthma and Chronic Obstructive Pulmonary Disorder

Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma

Repurposing old drugs to fight multidrug resistant cancers

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