Anti-asthmatic Drugs Research Articles

Budesonide Analogues Preserve Stem Cell Pluripotency and Delay 3D Gastruloid Development.

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as an anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

Molecular docking analysis of selected bioactive components of Glycyrrhiza glabra against bronchial asthma

Bronchial asthma is a chronic inflammatory disease of the lung by the combined action of various cytokines. As a result of the strong inflammatory response increased infiltration of cytokines result, damages respiratory epithelium, Hyperplasia of the trachealis muscle, and increased mucous production. Athimathura choornam is a promising drug used in all inflammatory conditions. Objective: To explore the efficacy of the Siddha formulation Athimathura choornam, an anti asthmatic drug using computational molecular docking analysis. Method: Based on the phytochemical study the active principles present in the plant Athimathuram were retrieved. 3D structure of the targets were retrieved from the repository and purified before the initiation of docking using the software. The potency of the drug was screened based on the binding of the ligands Asparagine, Liquiritin, and Glabridin with targets mentioned. These results were compared with the standard drugs such as Cetirizine, Salicylic acid, Diclofenac, Ibuprofen, and Celecoxib. Results and Conclusion: Liquiritin has 9 interactions (90%) similar to that of Ibuprofen, 14 interactions (90%) similar to that of Citrazinehence , 5 interactions (100%) similar to that of salicylic acid hence it has promising COX 1 inhibition ,Histamine 1 blocking activity and Prostaglandin Synthase inhibition activity. Asparagine has 3 interactions (60%) similar to Celecoxib, has promising COX 2 inhibition activity. Glabridin has 2 interactions (50%) similar to that of Diclofenac hence it has promising IL6 inhibition activity.

Synthesis of 1,3-Dienes via Ligand-Enabled Sequential Dehydrogenation of Aliphatic Acids.

1,3-Dienes are common scaffolds in biologically active natural products as well as building blocks for chemical synthesis. Developing efficient methods for the synthesis of diverse 1,3-dienes from simple starting materials is therefore highly desirable. Herein, we report a Pd(II)-catalyzed sequential dehydrogenation reaction of free aliphatic acids via β-methylene C-H activation, which enables one-step synthesis of diverse E,E-1,3-dienes. Free aliphatic acids of varying complexities, including the antiasthmatic drug seratrodast, were found to be compatible with the reported protocol. Considering the high lability of 1,3-dienes and lack of protecting strategies, dehydrogenation of aliphatic acids to reveal 1,3-dienes at the late stage of synthesis offers an appealing strategy for the synthesis of complex molecules containing such motifs.

Inhaled pan-phosphodiesterase inhibitors ameliorate ovalbumin-induced airway inflammation and remodeling in murine model of allergic asthma.

Asthma is a heterogeneous, chronic respiratory disease characterized by airway inflammation and remodeling. Phosphodiesterase (PDE) inhibitors represent one of the intensively studied groups of potential anti-asthmatic agents due to their affecting both airway inflammation and remodeling. However, the effect of inhaled pan-PDE inhibitors on allergen induced asthma has not been reported to date. In this study we investigated the impact of two, representative strong pan-PDE inhibitors from the group of 7,8-disubstituted derivatives of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione: compound 38 and 145, on airway inflammation and remodeling in murine model of ovalbumin (OVA)-challenged allergic asthma. Female Balb/c mice were sensitized and challenged with OVA, 38 and 145 were administrated by inhalation, before each OVA challenge. The inhaled pan-PDE inhibitors markedly reduced the OVA-induced airway inflammatory cell infiltration, eosinophil recruitment, Th2 cytokine level in bronchoalveolar lavage fluid, as well as both, total and OVA-specific IgE levels in plasma. In addition, inhaled 38 and 145 decreased many typical features of airway remodeling, including goblet cell metaplasia, mucus hypersecretion, collagen overproduction and deposition, as well as Tgfb1, VEGF, and α-SMA expression in airways of allergen challenged mice. We also demonstrated that both 38 and 145 alleviate airway inflammation and remodelling by inhibition of the TGF-β/Smad signaling pathway activated in OVA-challenged mice. Taken together, these results suggest that the investigated pan-PDE inhibitors administered by inhalation are dual acting agents targeting both airway inflammation and remodeling in OVA-challenged allergic asthma and may represent promising, anti-asthmatic drug candidates.

The use of chitosan as an effective carrier of theophylline - an anti-asthmatic drug

In order to solve the problem of frequent drug dosing and increase its effectiveness, theophylline (THP) was deposited on chitosan nanoparticles (CSNPs). THP-CSNPs nanocomposites with the composition of 50, 75, 100 or 150 mg of chitosan (CS) and 25, 50, 75, 100 or 200 mg of tripolyphosphate (TPP) at pH 4.0, 5.0, 6.0 and 6.5 were prepared, and a constant weight of THP of 100 mg. The nanocomposites were characterized by X-ray diffraction (PXRD), field emission scanning electron microscopy (FE-SEM), and Fourier transform infrared spectroscopy (FTIR). The rate of drug release was also tested. The Minitab 18 program was used to analyze the results. The independent variables were the CS, TPP, and pH, while loading efficiency, zeta potential, and particle size were the dependent variables. The nanocomposites successfully transported and protected the drug, providing its sustained release.

Herbal medicine for the treatment of obesity-associated asthma: a comprehensive review.

Obesity is fast growing as a global pandemic and is associated with numerous comorbidities like cardiovascular disease, hypertension, diabetes, gastroesophageal reflux disease, sleep disorders, nephropathy, neuropathy, as well as asthma. Studies stated that obese asthmatic subjects suffer from an increased risk of asthma, and encounter severe symptoms due to a number of pathophysiology. It is very vital to understand the copious relationship between obesity and asthma, however, a clear and pinpoint pathogenesis underlying the association between obesity and asthma is scarce. There is a plethora of obesity-asthma etiologies reported viz., increased circulating pro-inflammatory adipokines like leptin, resistin, and decreased anti-inflammatory adipokines like adiponectin, depletion of ROS controller Nrf2/HO-1 axis, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) associated macrophage polarization, hypertrophy of WAT, activation of Notch signaling pathway, and dysregulated melanocortin pathway reported, however, there is a very limited number of reports that interrelates these pathophysiologies. Due to the underlying complex pathophysiologies exaggerated by obese conditions, obese asthmatics respond poorly to anti-asthmatic drugs. The poor response towards anti-asthmatic drugs may be due to the anti-asthmatics approach only that ignores the anti-obesity target. So, aiming only at the conventional anti-asthmatic targets in obese-asthmatics may prove to be futile until and unless treatment is directed towards ameliorating obesity pathogenesis for a holistic approach towards amelioration of obesity-associated asthma. Herbal medicines for obesity as well as obesity-associated comorbidities are fast becoming safer and more effective alternatives to conventional drugs due to their multitargeted approach with fewer adverse effects. Although, herbal medicines are widely used for obesity-associated comorbidities, however, a limited number of herbal medicines have been scientifically validated and reported against obesity-associated asthma. Notable among them are quercetin, curcumin, geraniol, resveratrol, β-Caryophyllene, celastrol, tomatidine to name a few. In view of this, there is a dire need for a comprehensive review that may summarize the role of bioactive phytoconstituents from different sources like plants, marine as well as essential oils in terms of their therapeutic mechanisms. So, this review aims to critically discuss the therapeutic role of herbal medicine in the form of bioactive phytoconstituents against obesity-associated asthma available in the scientific literature to date.

Drugs Prescribed for Asthma and Their Adverse Effects on Dental Health

Asthma is a chronic, heterogeneous respiratory pathology characterized by reversible airway inflammation. Therapeutics focus on symptom reduction and control, aimed at preserving normal pulmonary function and inducing bronchodilatation. The objective of this review is to describe the adverse effects produced by anti-asthmatic drugs on dental health, according to the reported scientific evidence. A bibliographic review was carried out on databases, such as Web of science, Scopus, and ScienceDirect. Most anti-asthmatic medications are administered using inhalers or nebulizers, making it impossible to avoid contact of the drug with hard dental tissues and oral mucosa, and thus promoting a greater risk of oral alterations, mainly due to decreases in the salivary flow and pH. Such changes can cause diseases, such as dental caries, dental erosion, tooth loss, periodontal disease, bone resorption, as well as fungal infections, such as oral candidiasis.

Analysis of the Pharmaceutical Market of Drugs Used in the Pharmacotherapy of Bronchial Asthma in the Kyrgyz Republic

The article presents the results of the analysis of the pharmaceutical market of drugs used in the pharmacotherapy of bronchial asthma in the Kyrgyz Republic. The materials of the study were the pharmaceutical market of medicines used for the treatment of bronchial asthma in the Kyrgyz Republic, the data of the regulatory authority in the field of circulation of medicines and pharmaceutical organizations. Research results. It was established that in the Kyrgyz Republic the analyzed group of drugs included in the clinical protocol for the treatment of bronchial asthma is represented by 56 trade names. In the nomenclature of drugs for the treatment of bronchial asthma, the leading place belongs to single drugs — 87.5%, the share of combined drugs, respectively, is 12.5%. Of the total number of anti-asthma drugs in the pharmaceutical market, lecotriene receptor antagonists rank first with a share of 46.29%, β2-agonists — 37%, combined glucocorticosteroids — 17.83%, inhaled glucocorticosteroids — 29.62% and glucocorticosteroids for systemic use — 24%, methylxanines — 9.25%, anticholinergics — 7.4%. Conclusion. Drugs for the treatment of bronchial asthma, present on the pharmaceutical market of the Kyrgyz Republic, in general, comply with the recommendations of the experts of the Global Initiative for Asthma (GINA) (Global Initiative for Asthma). All medicines on the pharmaceutical market of the Kyrgyz Republic are represented exclusively by foreign manufacturers, among which Turkey is the leader.

Effectiveness and economic impact of Dupilumab in asthma: a population-based cohort study

RationaleSevere asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed.ObjectivesTo evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma.MethodsData were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation (“post-intervention period”) and (i) the 6 months before Dupilumab initiation (“wash-out period”) and (ii) the corresponding 6 months of the prior year (“pre-intervention period”).Main resultsIn a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting β2-agonists, inhaled corticosteroids (ICS)/long-acting β2-agonists and ICS alone) when comparing the “pre-intervention” to the “post-intervention” period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the “pre-intervention” and “post-intervention” period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change.ConclusionsOur real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

N-Trifluoromethyl Succinimide as a New Reagent for Direct C-H Trifluoromethylation of Free Anilines.

N-trifluoromethylsuccinimide (NTFS) as a new trifluoromethylation reagent was designed and prepared via Ag-CF3 , and applied to the direct trifluoromethylation of free aniline, and a series of trifluoromethyl products were obtained with good yields. The practicability of the protocol was verified by a gram-level experiment and the synthesis of the antiasthmatic drug Mabuterol. In addition, a possible radical mechanism was proposed and verified by related experiments. The protocol provided a new solution for C-H trifluoromethylation of free anilines.

Electrochemical Sensors for the Detection of Anti-asthma Drugs in Pharmaceutical and Biological Fluids: A Review

Background: Worldwide, the prescriptions for asthma drugs are on the rise. However, antiasthma drugs have side effects and can lead to fatal death at higher doses. Quite often, these drugs are abused as growth promoters in poultry/livestock as well as by athletes to enhance their performance. Consequently, it is vital to design uncomplicated, portable, rapid and highly sensitive means of detecting these anti-asthma drugs in pharmaceutical formulations and other sample matrices. This review highlights the use of electrochemical sensors as alternative methods to conventional analytical techniques for detecting anti-asthma drugs in pharmaceuticals and biological fluids. Methods: Literature covering diverse detection methods for anti-asthma drugs were reviewed to provide background information in this area of research. Next, the literature survey focused primarily on the emergence of the nanotechnology platform, including the strengths and weaknesses of this approach. Finally, a perspective on the future direction of this method was summarized. Results: Electrochemical sensors offer several advantages over conventional methods, which require long and tedious extraction, pre-concentration and clean up steps. Moreover, electrochemical sensor techniques are less expensive, easy to operate and avoid the need for harmful reagents known to generate a huge amount of non-environmental friendly chemicals. Conclusion: Nanotechnology-based electrochemical sensors represent a promising platform for analysing anti-asthma drugs in pharmaceuticals and biological fluids given their beneficial effects such as low cost, use of less health hazardous materials, and compatibility with environmental health.

Paradigmenwechsel in der Asthmatherapie: neue Begriffe für ein neues Denken

There has been a paradigm shift in asthma treatment over the last decades: from symptom treatment to symptom prevention. This paradigm shift was made possible by the availability of disease-modifying anti-asthmatic drugs (DMAADs), particularly of inhaled steroids (either monotherapy as low-dosed as possible or in combination with slow-acting beta mimetics and/or slow-acting parasympatholytics), biologics and modern allergen immunotherapy (AIT). These drugs are not only highly effective but are also characterised by little adverse effects and sometimes even collateral efficacy (positive effects on typical asthma comorbidities). The aim of treatment with DMAADs is the induction and maintenance of asthma remission: a long-term abscence of symptoms and exacerbations, stable lung function and no need for systemic steroids for asthma treatment. This new term of asthma remission differs from the term asthma control, which only refers to a short time period and can also be achieved by the administration of systemic steroids; however, systemic steroids should no longer be used in long-term asthma treatment because DMAADs are a more effective treatment option with less side effects.

Montelukast activates BK channels associated with the β4 accessory subunit and emerges as a pharmacological tool to reduce hippocampal excitability.

Different β accessory subunits are associated with the large conductance voltage- and Ca2+- dependent K+ channel (BK) in a tissue-specific manner. In particular, BK channel/β4 subunits complexes (α/β4) control neuronal excitability in granule cells of the hippocampal dentate gyrus (GCDG) and, β4 deficient mice display a temporal lobe epilepsy (TLE). Thus, compounds that increase α/β4 activity are of interest for improving epilepsy treatment. Then, based on the β-dependent activating effect of leukotrienes on BK channel, we explore the effect of Montelukast (MTK) on this channel heterologously expressed in HEK cells with or without its β accessory subunits (β1, β2, and β4). MTK is a CysLT1 receptor antagonist used as an anti-asthmatic drug that could share the affinity properties with the leukotrienes. Using the patch-clamp technique we found that MTK shifts the activation curves of α/β1 and α/β4 to more hyperpolarized voltages in a concentration-dependent manner (300 nM MTK: ΔV1/2 (α/β1)= −54.4 ± 8.4 mV; n=6; p<0.05 and ΔV1/2 (α/β4)= −36 ± 13.5 mV; n=5; p<0.05) without affecting α/β2 channel and, only at concentrations greater than 1 µM, slightly shifts the homomeric BK channel curve (ΔV1/2= −10.8 ± 3.7 mV; n=3; p<0.05). MTK delays α/β4 deactivation, suggesting an open channel stabilization (1 µM MTK (−60 mV): τMTK= 27.6 ± 3.7 ms vs. τcontrol= 2.0 ± 0.3 ms n= 5, p<0.05). Finally, as a promising result, we observed that 1 µM MTK decreases the number of action potential spikes induced by 140 pA injection in GCDG from mouse brain slices (58 ± 8%, n=3, p<0.05). Our results indicate that MTK directly activates the α/β4 channel and suggest that it could reduce GCDG excitability and may be a putative new treatment for TLE.

Assessing the national burden of allergic asthma by web-search data, pollen counts, and drug prescriptions in Germany and Sweden

BackgroundAsthma and its main phenotype allergic asthma are prevalent, chronic, and complex diseases affecting 4% of the population. One main trigger for allergic asthma exacerbations is pollen. Online health information search behavior by people is increasing, and analysis of web-search data can provide valuable insight into disease burden and risk factors of a population. ObjectivesWe sought to perform a web-search data analysis and correlation to climate factors and pollen in 2 European countries. MethodsWe analyzed the national web-search volume for allergic asthma-related keywords in Germany and Sweden from 2018 to 2021 and correlated it to local pollen counts, climatic factors, and drug prescription rates. ResultsPer capita, more searches were conducted in Sweden than in Germany. A complex geographic stratification within the countries was observed. Search results were seasonal with a peak in spring and correlated with pollen counts in both countries. However, anti-asthmatic drug prescription rates in Sweden, as well as temperature and precipitation in both countries, did not correlate with search volume. ConclusionOur analysis offers population-level insights about this complex disease by reporting its needs and establishing the correlation to pollen counts, which enables a targeted approach in the public health management of allergic asthma. Local pollen counts, as opposed to temperature or precipitation, might be good predictors of allergic asthma disease burden.

Impact of asthma control on health related quality of life in Islamabad, Pakistan: A correlational study

Background: Asthma is a bronchial airways disease which is characterized by chronic inflammation and repetitive Asthma attacks. Quality of life is also affected by asthma control. Objective: The objective is to determine the correlation of the asthma control with the health-related quality of life in Asthma patients. Methods: This descriptive cross-sectional study was conducted at N.I.H Islamabad and Federal General Hospital Islamabad. The asthmatic patients who had suffered from asthma for at least 6 months and were aged between 15-40 years, had received anti-asthmatic drugs and should have had residence at Islamabad/Rawalpindi were included. The subjects having cardiac, pulmonary or traumatic shortness of breath, any dermatological issues and those undergoing surgery were excluded from the study. The quality of life of asthmatic people was calculated using Urdu version of Mini Asthma Quality of Life Questionnaire (AQLQ). The study was spread over 6 months and 100 asthmatic patients, calculated through G-Power, were selected in the survey through convenience sampling. Spearman's correlation statistics on SPSS was used to find relation between health related quality of life and control on asthma Results: Out of total patients, 31% asthma patients had uncontrolled asthma and 63% had partially control asthma symptoms and only 6% with controlled asthma. The correlational value of r = 0.886 shows a strong relationship between control on asthma and quality of life. P&lt;0.05 so relationship is strong and significant. Quality of Life was poorer when the asthma was uncontrolled (2.12± 0.36) and it was better (5.46±0.30) when asthma was controlled. Conclusion: The study concluded that the patient's with controlled asthma had better quality of life as compared to the patients with poor control on asthma symptoms. These asthmatic patients had poor quality of life in all domains of emotional, environmental and activity limitation.

Impact of the COVID-19 Pandemic on the Prescribing of Antiasthmatic Treatments in Portugal: A Nationwide Study

PurposeThe coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on everyday life, the environment, and health care services. A shift from in-person medical appointments to telemedicine was a main adjustment. Such changes can have repercussions on the control and management of chronic respiratory diseases, such as asthma. The available data suggest that there was an overall decrease in asthma-related morbidities during the first year of the pandemic. Therefore, the goal of this study was to quantify the effects of the pandemic on the prescribing of antiasthmatic treatments in outpatient care (public and private health care). MethodsThis before–after study used a time series approach based on data from monthly prescriptions of antiasthmatic drugs (anti-inflammatory drugs and bronchodilators) dated between April 2018 and March 2021. An interrupted time series (ITS) design was used for assessing changes in antiasthmatic prescribing patterns in the short and long terms after COVID-19 was recognized as a pandemic. The results are complemented with seasonal autoregressive integrated moving average (sARIMA) models. FindingsThe ITS analysis showed a non-significant increase in antiasthmatic prescribing in the short term. In the long term, after the pandemic was declared, a statistically significant decrease was observed in the prescribing of antiasthmatics (in anti-inflammatory drugs and, more pronounced, in bronchodilators). In the sARIMA model, the mean monthly volume of antiasthmatic prescriptions was 18.1% lower than predicted. The numbers of months outside of the 95% CIs were different between anti-inflammatory drugs (1 month) and bronchodilators (7 months). ImplicationsThe prescribing of antiasthmatic drugs in the long term was significantly decreased with the COVID-19 pandemic, with a greater effect in the case of bronchodilators.

СУЧАСНІ ПІДХОДИ ЛІКУВАННЯ БРОНХІАЛЬНОЇ АСТМИ ЗГІДНО GINA 2023

In 1993 there was initiated the Global Initiative for Asthma Management and Prevention. Each year GINA is revised and each subsequent revision contains updated recommendations based on new data. It’s underlined in red throughout GINA 2023 the significance of ICScontaining therapy. The best treatment approach for adults and adolescents remains Track 1 with ICS/formoterol as needed. Track 2 now also includes an ICS/SABA combination as needed as an Anti-inflammatory Reliever (AIR), but Track 1 remains the “preferred” regimen. Although inhaled SABA are highly effective for rapid relief of asthma symptoms, patients whose asthma is treated with SABA alone (compared with ICS) have an increased risk of death and asthma-related emergency medical care needs. For safety reasons, GINA does not recommend SABA alone for the treatment of asthma in adults, adolescents, or children 6–11 years of age. Is it possible to treat asthma without SABA? In an asthma center in Argentina, since 2014, a treatment strategy with ICS-containing symptom relievers has been implemented: using only budesonide/formoterol in a single inhaler across all spectrums of asthma severity and completely excluding the use of SABA. As a result, the level of hospitalization decreased by 92%. The 2023 revision of GINA proposed new terminology for anti-asthma drugs: Maintenance therapy, controller drugs, reliever drugs, anti-inflammatory reliever, Maintenance and Reliever Therapy - MART. Clarifications have been made for the treatment of asthma exacerbations. Added details on drugs and doses of ICS/formoterol on demand and ICS/SABA as needed, MART regimen in individual asthma action plan, how and when to modify these drugs as the disease worsens. The inhaler prescription algorithm is written in more details, considering its impact on the environment. Conclusions: The GINA 2023 updates highlight the most significant role of ICS-containing therapy in achieving asthma control and preventing exacerbations. However, patient adherence to therapy remains quite low, so an approach that allows for the management of both symptoms and exacerbations simultaneously is simpler and remains the preferred way of asthma therapy. Global approaches to asthma management - limiting, where possible, the use of SABA and favoring delivery devices and treatment regimens with less environmental impact. Managing the patient according to his personal action plan and creating local protocols can limit the use of SABA, improve the patient’s asthma outcomes and environmental impact. Key words: asthma, GINA, inhalers, asthma control, exacerbation

Trends of therapy in the treatment of asthma.

To better understand the development of therapy for asthma, grasp the core paradigm associated with the transformation of cognition of asthma treatment and asthma, explore potential and effective therapies for asthma, discover new biomarkers and mechanisms related to asthma treatment, find novel targets for anti-asthma drugs, and predict the future trends of asthma therapy, we used a bibliometric analysis to research articles related to the therapies for asthma published from 1983 to 2022. A comprehensive search was conducted to analyze the articles associated with therapy for asthma with the help of the Web of Science Core Collection (WOSCC) database from January 1, 1983 to August 14, 2022. The CiteSpace 6.1.R2 software and VOS viewer 6.1.8 software were utilized to analyze the overall structure of the network, network clusters, links between clusters, key nodes, and pathways. A total of 3902 publications related to therapies on asthma were published in 3211 academic journals by a total of 14,655 authors in 3476 organizations from 87 countries or regions from 1983 to 2022. The United States published the most articles (n = 1143), followed by England (n = 574) and China (n = 405). However, the centrality of China was 0.4, higher than the United States (centrality = 0.16) and Singapore (centrality = 0.11). Akdis Cezmi published the most papers. Journal of Allergy and Clinical Immunology published the most studies on therapies for asthma. Asthma was the most frequent keyword (n = 594). The betweenness centrality value of keywords that were greater than 0.1 included airway inflammation (centrality = 0.22), double blind (centrality = 0.18), asthma (centrality = 0.17), inflammation (centrality = 0.12), and inhaled corticosteroid (centrality = 0.11). The results from this biometric review provide insight into the development of therapy for asthma, the paradigm of recognition of this field, the approach of discovering new targets, exploration and combination of new mechanisms, and the frontier trend of this field in future.

Molecular dynamics study on the behavior and binding mechanism of target protein Transgelin-2 with its agonist TSG12 for anti-asthma drug discovery

Transgelin-2 (TG2) is a novel promising therapeutic target for the treatment of asthma as it plays an important role in relaxing airway smooth muscles and reducing pulmonary resistance in asthma. The compound TSG12 is the only reported TG2 agonist with in vivo anti-asthma activity. However, the dynamic behavior and ligand binding sites of TG2 and its binding mechanism with TSG12 remain unclear. In this study, we performed 12.6 μs molecular dynamics (MD) simulations for apo-TG2 and TG2-TSG12 complex, respectively. The results suggested that the apo-TG2 has 4 most populated conformations, and that its binding of the agonist could expand the conformation distribution space of the protein. The simulations revealed 3 potential binding sites in 3 most populated conformations, one of which is induced by the agonist binding. Free energy decomposition uncovered 8 important residues with contributions stronger than −1 kcal/mol. Computational alanine scanning for the important residues by 100 ns conventional MD simulation for each mutated TG2-TSG12 complexes demonstrated that E27, R49 and F52 are essential residues for the agonist binding. These results should be helpful to understand the dynamic behavior of TG2 and its binding mechanism with the agonist TSG12, which could provide some structural insights into the novel mechanism for anti-asthma drug development.