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International Journal of Molecular... Oct 2022Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in...
Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-β in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student's -test or Welch's -test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ( = 0.0072), ( = 0.0002) and ( = 0.0204), and 1,25(OH)D had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of expression ( = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-β) control group ( = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs.
Topics: Humans; Airway Remodeling; Calcitriol; Vimentin; Anti-Asthmatic Agents; Vitamin D; Leukotriene D4; Vitamins; Transforming Growth Factor beta; ADAM Proteins
PubMed: 36361588
DOI: 10.3390/ijms232112798 -
Survey of Ophthalmology 2024Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and... (Review)
Review
Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and young adults. Prevalence varies by region, ranging from <2 per 10,000 in the United States to as high as 1,100 per 10,000 in parts of Africa. The rarity of VKC in developed countries can make differential diagnosis challenging, and treatment is often delayed until the disease is advanced, and symptoms are significantly impacting patients' quality of life. Although once viewed primarily as an immunoglobulin E-mediated condition, approximately 50% of patients with VKC do not exhibit allergic sensitization. It is now recognized that the immunopathology of VKC involves multiple inflammatory pathways that lead to the signs, symptoms, and conjunctival eosinophilic and fibroproliferative lesions that are a hallmark of the disease. We examine the evolution of our understanding of the immunopathology of VKC, the expanding VKC treatment armamentarium, the clinical implications of emerging treatment approaches, and future directions for VKC research and practice.
Topics: Child; Humans; Conjunctivitis, Allergic; Cyclosporine; Quality of Life; Conjunctiva; Ophthalmic Solutions
PubMed: 37890678
DOI: 10.1016/j.survophthal.2023.10.008 -
ELife Mar 2022The SARS-CoV-2 non-structural protein 1 (Nsp1) contains an N-terminal domain and C-terminal helices connected by a short linker region. The C-terminal helices of Nsp1...
The SARS-CoV-2 non-structural protein 1 (Nsp1) contains an N-terminal domain and C-terminal helices connected by a short linker region. The C-terminal helices of Nsp1 (Nsp1-C-ter) from SARS-CoV-2 bind in the mRNA entry channel of the 40S ribosomal subunit and blocks mRNA entry, thereby shutting down host protein synthesis. Nsp1 suppresses host immune function and is vital for viral replication. Hence, Nsp1 appears to be an attractive target for therapeutics. In this study, we have in silico screened Food and Drug Administration (FDA)-approved drugs against Nsp1-C-ter. Among the top hits obtained, montelukast sodium hydrate binds to Nsp1 with a binding affinity (K) of 10.8 ± 0.2 µM in vitro. Nsp1-C-ter in simulation runs . Montelukast sodium hydrate also rescues the inhibitory effect of Nsp1 in host protein synthesis, as demonstrated by the expression of firefly luciferase reporter gene in cells. Importantly, it shows antiviral activity against SARS-CoV-2 with reduced viral replication in HEK cells expressing ACE2 and Vero-E6 cells. We, therefore, propose montelukast sodium hydrate can be used as a lead molecule to design potent inhibitors to help combat SARS-CoV-2 infection.
Topics: Antiviral Agents; Drug Delivery Systems; Humans; Pharmaceutical Preparations; RNA, Messenger; SARS-CoV-2; Viral Nonstructural Proteins; COVID-19 Drug Treatment
PubMed: 35323109
DOI: 10.7554/eLife.74877 -
Viruses Apr 2022Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of...
Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.
Topics: Acetates; Animals; Coronavirus OC43, Human; Cyclopropanes; Middle East Respiratory Syndrome Coronavirus; Quinolines; SARS-CoV-2; Sulfides; COVID-19 Drug Treatment
PubMed: 35632604
DOI: 10.3390/v14050861 -
American Journal of Translational... 2021The aim of this study is to explore the clinical efficacy of montelukast sodium (MKST) combined with budesonide (BUD) on children with cough variant asthma (CVA) and its...
OBJECTIVE
The aim of this study is to explore the clinical efficacy of montelukast sodium (MKST) combined with budesonide (BUD) on children with cough variant asthma (CVA) and its influence on inflammation and pulmonary function (PF).
METHODS
One hundred and sixty-six children with CVA treated in the Affiliated Nanhua Hospital, University of South China from May 2017 to August 2019 were randomized into a joint group (JG, n=92) for the combination therapy of MKST and BUD, and a control group (CG, n=74) for BUD monotherapy. Their clinical symptoms, total response rates (RR), PF, and inflammatory factor expressions were evaluated before and after treatment. The adverse reactions during the treatment were statistically compared between the two groups, and the factors influencing the curative effect were analyzed using logistic regression.
RESULTS
The JG presented markedly less cough resolution times, expectoration and wheezing, and a shorter body temperature recovery time than the CG after the treatment. The post-treatment forced expiratory volume in 1 second (FEV1), the forced vital capacity (FVC), the FEV1/FVC and the peak expiratory flow (PEF) levels as well as the Asthma Control Test (ACT) scores were statistically higher in the JG than in the CG. The JG had notably lower IgE, TNF-α, and IL-8 levels than the CG after the treatment. The total RR in the JG was observably higher than it was in the CG after the treatment, but the total adverse reaction rate identified no evident difference between the two series. Children with a family history of allergies, a family medical history, low ACT scores, high IgE expressions, high TNF-α expressions, and high IL-8 expressions, as well as BUD intervention are at increased risk of reduced efficacy.
CONCLUSIONS
The reduction of efficacy in children with CVA results from multiple risk factors. MKST combined with BUD can ameliorate the PF of children with CVA, reduce their inflammatory factors, and improve the curative effect and the prognosis.
PubMed: 34306431
DOI: No ID Found -
RSC Advances Nov 2023Supercritical carbon dioxide (SC-CO)-based approaches have become more popular in recent years as alternative methods for creating micro- or nanosized medicines....
Supercritical carbon dioxide (SC-CO)-based approaches have become more popular in recent years as alternative methods for creating micro- or nanosized medicines. Particularly, high drug solubility is required in those techniques using SC-CO as a solvent. During the most recent pandemic years, favipiravir and montelukast were two of the most often prescribed medications for the treatment of COVID-19. In this study, ethanol at 1 and 3 mol% was utilized as a cosolvent to increase the solubility of both medicines in SC-CO by a static approach using a range of temperatures (308 to 338 K) and pressure (12 to 30 MPa) values. The experimentally determined solubilities of favipiravir and montelukast in SC-CO + 3 mol% ethanol showed solubility values up to 33.3 and 24.5 times higher than that obtained for these drugs with only SC-CO. The highest values were achieved in the pressure of 12 MPa and temperature of 338 K. Last but not least, six density-based semi-empirical models with various adjustable parameters were used to perform the modeling of the solubility of favipiravir and montelukast.
PubMed: 38020033
DOI: 10.1039/d3ra05484e -
Journal of Clinical Sleep Medicine :... Oct 2022Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and...
STUDY OBJECTIVES
Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and pulmonary function on polysomnography in children with asthma.
METHODS
We conducted a retrospective chart review on 448 7- to 18-year-old children with asthma who had undergone polysomnography testing between 1/2007-12/2011 to elucidate the association between spirometry variables, body-mass index, and polysomnography parameters, adjusting for asthma and antiallergic medications.
RESULTS
Obese children had poorer sleep architecture and more severe gas exchange abnormalities compared to healthy weight children. Multivariate analysis revealed an independent association of body-mass index with sleep efficiency, with more light and less deep sleep in both obese and healthy-weight children, and with baseline oxygen saturation and oxygen nadir in obese children. In obese children, forced vital capacity was independently associated with less deep sleep (time in N3 sleep) as well as with oxygen nadir, while among healthy-weight children, forced expiratory volume directly correlated but forced vital capacity inversely correlated with deep sleep. In obese children, inhaled corticosteroid was associated with baseline oxygen saturation, and montelukast was associated with lower end-tidal carbon dioxide. In healthy-weight children, inhaled corticosteroid was associated with arousal awakening index, and montelukast was associated with light sleep. Antiallergic medications were not independently associated with polysomnography parameters.
CONCLUSIONS
Pulmonary function, body-mass index, and asthma medications have independent and differing influences on sleep architecture and gas exchange polysomnography parameters in obese and healthy-weight children with asthma. Asthma medications are associated with improved gas exchange in obese children and improved sleep architecture in healthy-weight children with asthma.
CITATION
Conrad LA, Nandalike K, Rani S, Rastogi D. Associations between sleep, obesity, and asthma in urban minority children. . 2022;18(10):2377-2385.
Topics: Acetates; Adolescent; Adrenal Cortex Hormones; Anti-Allergic Agents; Asthma; Body Mass Index; Carbon Dioxide; Child; Cyclopropanes; Humans; Oxygen; Pediatric Obesity; Quinolines; Retrospective Studies; Sleep; Sulfides
PubMed: 35801341
DOI: 10.5664/jcsm.10114 -
Frontiers in Pharmacology 2020Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology....
Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology. Given that cardiovascular disease has a critical inflammatory component, the aim of this work was to conduct an observational study to verify whether the use of a cysteinyl leukotriene antagonist, namely, montelukast, may protect asthmatic patients from a major cardiovascular event and, therefore, represent an innovative adjunct therapy to target an inflammatory component in cardiovascular disease. We performed an observational retrospective 3-year study on eight hundred adult asthmatic patients 18 years or older in Albania, equally distributed into two cohorts, exposed or nonexposed to montelukast usage, matched by age and gender according to information reported in the data collection. Patients with a previous history of myocardial infarction or ischemic stroke were excluded. In summary, 37 (4.6%) of the asthmatic patients, 32 nonexposed, and five exposed to montelukast suffered a major cardiovascular event during the 3-year observation period. All the cardiovascular events, in either group, occurred among patients with an increased cardiovascular risk. Our analyses demonstrate that, independent from gender, exposure to montelukast remained a significant protective factor for incident ischemic events (78% or 76% risk reduction depending on type of analysis). The event-free Kaplan-Meier survival curves confirmed the lower cardiovascular event incidence in patients exposed to montelukast. Our data suggest that there is a potential preventative role of montelukast for incident cardiac ischemic events in the older asthmatic population, indicating a comorbidity benefit of montelukast usage in asthmatics by targeting cysteinyl leukotriene-driven cardiac disease inflammation.
PubMed: 33519477
DOI: 10.3389/fphar.2020.611561 -
Indian Journal of Dermatology 2016Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity.... (Review)
Review
Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU.
PubMed: 27293247
DOI: 10.4103/0019-5154.182406 -
Annals of Medicine and Surgery (2012) Jun 2024Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney... (Review)
Review
INTRODUCTION
Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney function, while chronic kidney disease involves a gradual deterioration lasting more than 3 months. Mechanisms of renal injury include impaired microcirculation, inflammation, and oxidative stress. Cysteinyl-leukotrienes (CysLTs) are inflammatory substances contributing to tissue damage. Montelukast, a leukotriene receptor antagonist, has shown potential renoprotective effects in experimental models of kidney injury.
METHODS
The authors conducted a scoping review using PubMed, Scopus, and Web of Science databases to identify relevant studies investigating the impact of montelukast on renal diseases. Articles published until 2022 were included and evaluated for quality. Data extraction and analysis were performed based on predetermined inclusion criteria.
RESULTS
The scoping review included 30 studies from 8 countries. Montelukast demonstrated therapeutic effects in various experimental models of nephrotoxicity and AKI induced by agents such as cisplatin, lipopolysaccharide, diclofenac, amikacin, , cyclosporine, methotrexate, cobalt-60 gamma radiation, doxorubicin, and cadmium. Studies involving human subjects with nephrotic syndrome, pyelonephritis, and other renal diseases also reported positive outcomes with montelukast treatment. Montelukast exhibited anti-inflammatory, anti-apoptotic, antioxidant, and neutrophil-inhibiting properties, leading to improved kidney function and histopathological changes.
CONCLUSIONS
Montelukast shows promise as a renoprotective medication, particularly in early-stage kidney injury. Its ability to mitigate inflammation, oxidative stress, and neutrophil infiltration contributes to its therapeutic effects. Further research is needed to explore the clinical applications and mechanisms underlying the renoprotective action of montelukast.
PubMed: 38846849
DOI: 10.1097/MS9.0000000000002085