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Search Results (646)

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27 pages, 1201 KiB  
Review
Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients
by Aitor Gonzaga, Gema Martinez-Navarrete, Loreto Macia, Marga Anton-Bonete, Gladys Cahuana, Juan R. Tejedo, Vanessa Zorrilla-Muñoz, Eduardo Fernandez-Jover, Etelvina Andreu, Cristina Eguizabal, Antonio Pérez-Martínez, Carlos Solano, Luis Manuel Hernández-Blasco and Bernat Soria
Biomedicines 2025, 13(8), 1801; https://doi.org/10.3390/biomedicines13081801 - 23 Jul 2025
Abstract
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). [...] Read more.
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article
(This article belongs to the Section Gene and Cell Therapy)
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23 pages, 4250 KiB  
Article
Too Much SAMA, Too Many Exacerbations: A Call for Caution in Asthma
by Fernando M. Navarro Ros and José David Maya Viejo
J. Clin. Med. 2025, 14(14), 5046; https://doi.org/10.3390/jcm14145046 - 16 Jul 2025
Viewed by 342
Abstract
Background/Objectives: The overuse of short-acting β2-agonists (SABAs) has been associated with increased asthma morbidity and mortality, prompting changes in treatment guidelines. However, the role of frequent short-acting muscarinic antagonists (SAMAs) use remains poorly defined and unaddressed in current recommendations. This study [...] Read more.
Background/Objectives: The overuse of short-acting β2-agonists (SABAs) has been associated with increased asthma morbidity and mortality, prompting changes in treatment guidelines. However, the role of frequent short-acting muscarinic antagonists (SAMAs) use remains poorly defined and unaddressed in current recommendations. This study offers the first real-world analysis of SAMA overuse in asthma, quantifying its association with exacerbation risk and healthcare utilization and comparing its predictive value to that of SABAs. Methods: A retrospective multicenter cohort study analyzed electronic health records (EHRs) from 132 adults with asthma in the Spanish National Health System (SNS). Associations between annual SAMA use and clinical outcomes were assessed using negative binomial regression and 5000-sample bootstrap simulations. Interaction and threshold models were applied to explore how SAMA use affected outcomes and identify clinically actionable cutoffs. Results: SAMA use was independently associated with a 19.2% increase in exacerbation frequency per canister and a nearly sixfold increase in the odds of experiencing ≥1 exacerbation (OR = 5.97; 95% CI: 2.43–14.66). An inflection point at 2.5 canisters/year marked the threshold beyond which annual exacerbations exceeded one. Increased SAMA use was also associated with a higher number of respiratory consultations and with more frequent prescriptions of systemic corticosteroids and antibiotics. The risk increased more sharply with SAMAs than with SABAs, and the lack of correlation between them suggests distinct clinical patterns underlying their use. Conclusions: SAMA use emerges as a digitally traceable and clinically meaningful indicator of asthma instability. While the associations observed are robust and consistent across multiple outcomes, they should be considered provisional due to the study’s retrospective design and limited sample size. Replication in larger and more diverse cohorts is needed to confirm external validity. These findings support the integration of SAMA tracking into asthma management tools—alongside SABAs—to enable the earlier identification of uncontrolled disease and guide therapeutic adjustment. Full article
(This article belongs to the Special Issue New Clinical Advances in Chronic Asthma)
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29 pages, 3105 KiB  
Review
Uncaria tomentosa as a Promising Natural Source of Molecules with Multiple Activities: Review of Its Ethnomedicinal Uses, Phytochemistry and Pharmacology
by Olinda Marques, Artur Figueirinha, Maria Eugénia Pina and Maria Teresa Batista
Int. J. Mol. Sci. 2025, 26(14), 6758; https://doi.org/10.3390/ijms26146758 - 15 Jul 2025
Viewed by 263
Abstract
Uncaria tomentosa (Ut) is a Rubiaceae widely used in Peru’s traditional medicine. It is mainly known by the vernacular name of Cat’s claw due to its morphological aspects and is found in tropical low mountain forests of Central and South America. [...] Read more.
Uncaria tomentosa (Ut) is a Rubiaceae widely used in Peru’s traditional medicine. It is mainly known by the vernacular name of Cat’s claw due to its morphological aspects and is found in tropical low mountain forests of Central and South America. A decoction of Ut bark, root and leaves is used traditionally for different health problems, including arthritis, weakness, viral infections, skin disorders, abscesses, allergies, asthma, cancer, fevers, gastric ulcers, haemorrhages, inflammations, menstrual irregularity, rheumatism, urinary tract inflammation and wounds, among others, which gave rise to scientific and commercial interest. The present paper reviews research progress relating to the ethnobotany, phytochemistry and pharmacology of Ut, and some promising research routes are also discussed. We highlight the centrality of its different biological activities, such as antioxidant, anti-inflammatory, antiproliferative, antiviral, and antinociceptive, among others. Recently, studies of the health effects of this plant suggest that novel nutraceuticals can be obtained from it and applied as a preventive or prophylaxis strategy before the start of conventional drug therapy, especially for patients who are not prone to conventional pharmacological approaches to diseases. The present work emphasizes the current pharmacological properties of Uncaria tomentosa, evidencing its therapeutic benefits and encouraging further research on this medicinal plant. Full article
(This article belongs to the Special Issue Current Research in Pharmacognosy: A Focus on Biological Activities)
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27 pages, 583 KiB  
Review
Non-Coding RNAs in Asthma: Regulators of Eosinophil Biology and Airway Inflammation
by Eglė Vasylė, Andrius Januškevičius and Kęstutis Malakauskas
Diagnostics 2025, 15(14), 1750; https://doi.org/10.3390/diagnostics15141750 - 10 Jul 2025
Viewed by 376
Abstract
Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction. Despite extensive research, its underlying molecular mechanisms remain incompletely understood. Among the key immune cells involved, eosinophils play a central role in asthma pathophysiology through [...] Read more.
Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction. Despite extensive research, its underlying molecular mechanisms remain incompletely understood. Among the key immune cells involved, eosinophils play a central role in asthma pathophysiology through their contributions to Type 2 inflammation, tissue remodeling, and immune regulation. Recent studies have shown that non-coding RNAs (ncRNAs) play a crucial role in regulating eosinophil biology and contribute to the molecular mechanisms underlying asthma progression. This review consolidates the current understanding of ncRNAs in the development of eosinophils, their involvement in asthma pathogenesis, and the mechanisms underlying this process. Full article
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21 pages, 719 KiB  
Review
Biologic Therapy in Severe Asthma: A Phenotype-Driven and Targeted Approach
by Maria D’Amato, Daniela Pastore, Chiara Lupia, Claudio Candia, Andrea Bruni, Eugenio Garofalo, Federico Longhini, Angelantonio Maglio, Albino Petrone, Alessandro Vatrella, Girolamo Pelaia and Corrado Pelaia
J. Clin. Med. 2025, 14(13), 4749; https://doi.org/10.3390/jcm14134749 - 4 Jul 2025
Viewed by 673
Abstract
Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced [...] Read more.
Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article
(This article belongs to the Special Issue New Clinical Advances in Chronic Asthma)
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12 pages, 237 KiB  
Article
Teacher Self-Efficacy in Asthma Management in Elementary and Middle Schools
by Ethan Schilling, Stacey Neuharth-Pritchett, Sofia H. Davie and Yvette Q. Getch
Allergies 2025, 5(3), 25; https://doi.org/10.3390/allergies5030025 - 3 Jul 2025
Viewed by 330
Abstract
Background/Objectives: This study assessed teacher self-efficacy in school-based asthma management in two southern states in the United States. Current literature focuses primarily on supporting school-based asthma management, but few studies have focused on teacher self-efficacy in the asthma management process. Methods: With data [...] Read more.
Background/Objectives: This study assessed teacher self-efficacy in school-based asthma management in two southern states in the United States. Current literature focuses primarily on supporting school-based asthma management, but few studies have focused on teacher self-efficacy in the asthma management process. Methods: With data collected from a two-state survey of a randomly selected group of teachers in grades kindergarten to grade eight (n = 379), teachers’ demographic variables, general opinions about asthma management practices, and their self-perceptions on the Teacher Asthma Management and Information Seeking Scale, which assesses self-efficacy, were examined. Results: Teachers’ self-efficacy in managing asthma and seeking information was significantly higher among teachers who had completed in-service professional learning sessions and those who had access to community resources or links to community agencies. Additionally, teachers with personal experience of chronic illness, asthma, or allergies and those who had students with chronic illnesses in their classrooms reported higher self-efficacy scores. Conclusions: Findings suggest that providing professional learning about asthma for teachers, offering access to asthma action plans and community resources, and increasing awareness of chronic conditions and training for handling medical emergencies can enhance teachers’ self-efficacy and improve outcomes for students with chronic illnesses. Full article
(This article belongs to the Section Asthma/Respiratory)
22 pages, 6303 KiB  
Article
A Novel Regulatory Role for RPS4Y1 in Inflammatory and Fibrotic Processes
by Karosham D. Reddy, Senani N. H. Rathnayake, Sobia Idrees, Fia Boedijono, Dikaia Xenaki, Matthew P. Padula, Maarten van den Berge, Alen Faiz and Brian G. G. Oliver
Int. J. Mol. Sci. 2025, 26(13), 6213; https://doi.org/10.3390/ijms26136213 - 27 Jun 2025
Viewed by 383
Abstract
Asthma is a chronic inflammatory respiratory disease well-known to demonstrate sexual dimorphism in incidence and severity, although the mechanisms causing these differences remain incompletely understood. RPS4X and RPS4Y1 are X and Y-chromosome-linked genes coding ribosomal subunits previously associated with inflammation, airway remodelling and [...] Read more.
Asthma is a chronic inflammatory respiratory disease well-known to demonstrate sexual dimorphism in incidence and severity, although the mechanisms causing these differences remain incompletely understood. RPS4X and RPS4Y1 are X and Y-chromosome-linked genes coding ribosomal subunits previously associated with inflammation, airway remodelling and asthma medication efficacy. Particularly, RPS4Y1 has been under-investigated within the context of disease, with little examination of molecular mechanisms and pathways regulated by this gene. The ribosome, a vital cellular machinery, facilitates the translation of mRNA into peptides and then proteins. Imbalance or dysfunction in ribosomal components may lead to malfunctioning proteins. Using CRISPR-Cas9 knockout cellular models for RPS4Y1 and RPS4X, we characterised the function of RPS4Y1 in the context of the asthma-relevant processes, inflammation and fibrosis. No viable RPS4X knockouts could be generated. We highlight novel molecular mechanisms such as specific translation of IL6 and tenascin-C mRNA by RPS4Y1 containing ribosomes. Furthermore, an RPS4Y1-centric gene signature correlates with clinical lung function measurements, specifically in adult male asthma patients. These findings inform the current understanding of sex differences in asthma, as females do not produce the RPS4Y1 protein. Therefore, the pathologically relevant functions of RPS4Y1 may contribute to the complex sexually dimorphic pattern of asthma susceptibility and progression. Full article
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23 pages, 5089 KiB  
Review
Optimizing Airway Function Through Craniofacial and Cervical Manipulations and Emergency-Anesthesia Maneuvers: Applications in Airway Function Enhancement, Pneumonia, and Asthma—Narrative Review
by Jason Park, Luz Benitez, Amethyst Hamanaka, Ghulam Husain Abbas, Emmanuel Faluade, Sjaak Pouwels and Jamie Eller
J. Clin. Med. 2025, 14(13), 4494; https://doi.org/10.3390/jcm14134494 - 25 Jun 2025
Viewed by 557
Abstract
Background: Even with advanced management involving pharmacologic and ventilatory strategies, respiratory dysfunction increases morbidity and reduces the quality of life. This narrative review examines how craniofacial and cervical manipulative interventions—including nasomaxillary skeletal expansion, breathing re-education, and structural techniques—may holistically optimize airway function by [...] Read more.
Background: Even with advanced management involving pharmacologic and ventilatory strategies, respiratory dysfunction increases morbidity and reduces the quality of life. This narrative review examines how craniofacial and cervical manipulative interventions—including nasomaxillary skeletal expansion, breathing re-education, and structural techniques—may holistically optimize airway function by enhancing neurological and lymphatic dynamics, modulating vagal tone, reducing pharyngeal collapsibility, and supporting immune regulation across diverse clinical settings. Objectives: To explore manual techniques that influence respiratory and autonomic function and to evaluate their reported clinical efficacy and supporting evidence, particularly in the context of airway disorders such as asthma and pneumonia. Methods: A narrative review of the literature from PubMed and Google Scholar was conducted using search terms related to airway function and osteopathic manipulative techniques (OMTs). The inclusion criteria spanned 2010–2025 English-language peer-reviewed full-text articles on airway function, OMT, and emergency airway maneuvers. Clinical trials, observational studies, and reviews were included; non-peer-reviewed content and animal studies (unless mechanistically relevant) were excluded. Chapman’s reflexes related to respiratory function were incorporated to highlight somatic–visceral correlations. Key Findings: The techniques reviewed included frontal lift, vomer manipulation, maxillary and zygomatic balancing, and cervical adjustments. Thoracic OMT methods, such as diaphragm doming and lymphatic pump techniques, were also addressed. Emergency techniques, such as the BURP and Larson maneuvers, prone positioning, and high-frequency chest wall oscillation, were presented as comparative strategies to OMTs for acute airway management. Conclusions: Craniofacial and cervical manipulations can be a promising adjunct for enhancing airway function. However, the current literature displays heterogeneity and lack of large-scale randomized trials, which emphasize the necessity for standardized research and the establishment of clinical guidelines with the collected evidence. Full article
(This article belongs to the Section Respiratory Medicine)
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31 pages, 2254 KiB  
Review
Intestinal Microbiota in Early Life: Latest Findings Regarding the Role of Probiotics as a Treatment Approach for Dysbiosis
by Gabriel Florin Răzvan Mogoş, Monica Manciulea (Profir), Robert-Mihai Enache, Luciana Alexandra Pavelescu, Oana Alexandra Popescu (Roşu), Sanda Maria Cretoiu and Ileana Marinescu
Nutrients 2025, 17(13), 2071; https://doi.org/10.3390/nu17132071 - 21 Jun 2025
Viewed by 993
Abstract
The gut microbiota plays a crucial role in early-life development, influencing various aspects of health and disease. Dysbiosis, an imbalance in the gut microbiota, has been linked to multiple health conditions, including allergies, asthma, and obesity. In early life, the gut microbiota plays [...] Read more.
The gut microbiota plays a crucial role in early-life development, influencing various aspects of health and disease. Dysbiosis, an imbalance in the gut microbiota, has been linked to multiple health conditions, including allergies, asthma, and obesity. In early life, the gut microbiota plays a key role in the development and maturation of the immune system. Probiotics, live microorganisms that confer health benefits when administered in adequate amounts, have emerged as a potential treatment approach for dysbiosis in early life. Dysbiosis can alter the resistance to pathogens, promoting atopic diseases, food sensitization, and infections such as necrotizing enterocolitis (NEC). Probiotics have been shown to modulate the composition and function of the gut microbiota in the perinatal and infant periods. They can increase the abundance of beneficial bacteria, such as Bifidobacteria and Lactobacilli, and reduce the levels of potentially harmful bacteria. Not all probiotics are created equal. The effects of probiotics can vary depending on the specific strain used. Probiotics have also been investigated for their potential benefits in other areas of infant health, such as reducing the risk of respiratory infections and improving growth and development. This review aims to analyze the current data in the literature and to evaluate the health benefits of probiotic administration in early life. Several studies have investigated the use of probiotics in preventing or treating allergic diseases, such as eczema and food allergies. While some studies have shown promising results, more research is needed to fully understand the benefits and risks of probiotics in early life. In conclusion, using probiotics to prevent dysbiosis-related conditions may be considered a method of ‘programming’ the individual for optimal health maintenance. Full article
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22 pages, 1199 KiB  
Article
Assessment of Health Risks Associated with PM10 and PM2.5 Air Pollution in the City of Zvolen and Comparison with Selected Cities in the Slovak Republic
by Patrick Ivan, Marián Schwarz and Miriama Mikušová
Environments 2025, 12(7), 212; https://doi.org/10.3390/environments12070212 - 20 Jun 2025
Viewed by 675
Abstract
Air pollution is one of the most serious environmental threats, with particulate matter PM10 and PM2.5 representing its most harmful components, significantly affecting public health. These particles are primarily generated by transport, industry, residential heating, and agriculture, and are associated with [...] Read more.
Air pollution is one of the most serious environmental threats, with particulate matter PM10 and PM2.5 representing its most harmful components, significantly affecting public health. These particles are primarily generated by transport, industry, residential heating, and agriculture, and are associated with increased incidence of respiratory and cardiovascular diseases, asthma attacks, and heart attacks, as well as chronic illnesses and premature mortality. The most vulnerable groups include children, the elderly, and individuals with pre-existing health conditions. This study focuses on the analysis of health risks associated with PM10 and PM2.5 air pollution in the city of Zvolen, which serves as a representative case due to its urban structure, traffic load, and industrial activity. The aim is to assess the current state of air quality, identify the main sources of pollution, and evaluate the health impacts of particulate matter on the local population. The results will be compared with selected Slovak cities—Banská Bystrica and Ružomberok—to understand regional differences in exposure and its health consequences. The results revealed consistently elevated concentrations of particulate matter (PM) across all analyzed cities, frequently exceeding the guideline values recommended by the World Health Organization (WHO), although remaining below the thresholds set by current national legislation. The lowest average concentrations were recorded in the city of Zvolen (PM10: 20 μg/m3; PM2.5: 15 μg/m3). These lower values may be attributed to the location of the reference monitoring station operated by the Slovak Hydrometeorological Institute (SHMÚ), situated on J. Alexy Street in the southern part of the city—south of Zvolen’s primary industrial emitter, Kronospan. Due to predominantly southerly wind patterns, PM particles are transported northward, potentially leading to higher pollution loads in the northern areas of the city, which are currently not being monitored. We analyzed trends in PM10 and PM2.5 concentrations and their relationship with hospitalization data for respiratory diseases. The results indicate a clear correlation between the concentration of suspended particulate matter and the number of hospital admissions due to respiratory illnesses. Our findings thus confirm the significant adverse effects of particulate air pollution on population health and highlight the urgent need for systematic monitoring and effective measures to reduce emissions, particularly in urban areas. Full article
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21 pages, 4231 KiB  
Article
Microfungus Podosphaera fusca and the Fungus-like Organism Peronospora ficariae as Potential Inhalant Allergens in a Mouse Model of Asthma
by Piotr Wlaź, Katarzyna Socała, Marta Palusińska-Szysz, Urszula Świderska, Dominika Szczypior, Magdalena Krasowska and Agnieszka Szuster-Ciesielska
Cells 2025, 14(12), 914; https://doi.org/10.3390/cells14120914 - 17 Jun 2025
Viewed by 459
Abstract
Allergic conditions have surged to unprecedented levels globally, affecting approximately 30% of the population. Fungi are among the major sources of allergens, accounting for about 6% of respiratory issues. Identifying the causes of respiratory allergies is not always possible. Our study assessed the [...] Read more.
Allergic conditions have surged to unprecedented levels globally, affecting approximately 30% of the population. Fungi are among the major sources of allergens, accounting for about 6% of respiratory issues. Identifying the causes of respiratory allergies is not always possible. Our study assessed the capacity of two plant parasites, Podosphaera fusca and Peronospora ficariae, which infect Cucurbita pepo and Ficaria verna, to provoke inflammatory and asthmatic reactions in mouse models of acute and chronic asthma. We performed experiments by sensitizing mice through intranasal challenges with extracts from P. fusca and P. ficariae. Subsequently, we used ELISA tests to measure pro-inflammatory cytokines, including IL-4, IL-5, IL-13, TNF-α, and TGF-β. We evaluated specific IgE production through ELISA and examined histological changes in mouse lungs using hematoxylin-eosin staining. Our research revealed that P. fusca and P. ficariae induced significant production of all tested cytokines, increased specific IgE levels, and caused histological changes characteristic of acute and chronic asthma progression. Although weaker than the reference allergen ovalbumin, P. fusca and P. ficariae possess proinflammatory and asthma-inducing capabilities, indicating the potential to expand the current list of fungal allergens. Full article
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16 pages, 778 KiB  
Review
The Junction of Allergic Inflammation and Atherosclerosis: Pathways and Clinical Implications—A Review
by Mihaela Valcovici, Mihai Sorin Iacob, Abhinav Sharma, Ana Maria Pah, Lucretia Marin-Bancila, Marcel Mihai Vaduva Berceanu, Milan Daniel Velimirovici, Anca-Raluca Dinu, Simona Ruxanda Drăgan and Nilima Rajpal Kundnani
Life 2025, 15(6), 964; https://doi.org/10.3390/life15060964 - 16 Jun 2025
Viewed by 827
Abstract
Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the [...] Read more.
Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the phases of allergic pathology, the immunological mechanisms of atherosclerosis, and the clinical link between allergic diseases (asthma, atopic dermatitis, allergic rhinitis, and food allergy) and cardiovascular disease (CVD), along with future therapeutic perspectives. Material and Method: A literature search was conducted in PubMed, Google scholar; ScienceDirect, Scopus, and studies published between 2014–2024 were taken into consideration. Keywords included allergic inflammation, eosinophils, mast cells, reactive oxygen species, atherosclerosis, Th2 cells, and cytokines. Epidemiological studies and review articles were included. Results: Emerging evidence suggests that allergic inflammation contributes to atherosclerosis through interconnected mechanisms such as eosinophil activation, reactive oxygen species production, mast cell degranulation, and endothelial dysfunction. Th2-driven immune responses, which are mediated by cytokines such as IL-4, IL-5, and IL-13, as well as eosinophil activity and mast cell degranulation, play a crucial role in vascular inflammation and plaque progression. Additionally, changes in lipid metabolism contribute to this process. Epidemiological studies support this connection, indicating that patients with chronic allergic conditions such as asthma, allergic rhinitis, food allergy, and atopic dermatitis experience increased cardiovascular morbidity. However, most current data are observational, and our understanding of the underlying mechanisms in humans remains limited, often relying on insights gained from preclinical models. Conclusions: A potential mechanism for cardiovascular risk is suggested by the interaction between atherosclerosis and allergic inflammation. Promising alternatives for treating allergic inflammation and cardiovascular issues include novel treatments like cytokine inhibitors, mast cell stabilizers, and biologics that target certain pathways. Further research is necessary to see whether concentrating on allergy pathways could lead to innovative treatments for cardiovascular disorders or vice versa. Full article
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16 pages, 7040 KiB  
Article
Exploring the Potential Association Between Inhaled Corticosteroid and Face Aging Risk: A Mendelian Randomization Study
by Junpeng Li, Yaqiong Liu, Gujie Wu, Shanye Yin, Lin Cheng and Wenjun Deng
Pharmaceuticals 2025, 18(6), 846; https://doi.org/10.3390/ph18060846 - 5 Jun 2025
Viewed by 620
Abstract
Background: Asthma is one of the most prevalent chronic diseases, affecting more than 300 million individuals globally. Inhaled corticosteroids (ICSs) are recommended as the primary therapy for managing and preventing asthma symptoms in current treatment guidelines. However, long-term use of ICSs could [...] Read more.
Background: Asthma is one of the most prevalent chronic diseases, affecting more than 300 million individuals globally. Inhaled corticosteroids (ICSs) are recommended as the primary therapy for managing and preventing asthma symptoms in current treatment guidelines. However, long-term use of ICSs could lead to multiple side effects, including skin changes. Methods: We identified ICS target genes using DrugBank and DGIdb databases and derived genetic instruments from cis-eQTL data in whole-blood samples (n = 31,684). GWAS data for facial aging traits (n = 423,999) and plasma metabolites (1400 metabolites, n = 8000) were analyzed. DNA methylation QTL (mQTL) data were used to explore epigenetic regulation. Mendelian randomization (MR) and colocalization analyses were performed to assess causality and shared genetic loci. Results: MR analysis suggested a significant link between genetically proxied ICSs (ORMDL3) and face aging in the European population. Further mediation analysis indicated that 5-Hydroxylysine partially mediates the relationship between ICSs and face aging. In addition, our analysis revealed the pleiotropic association of some novel DNA methylation sites of ORMDL3 with face aging, suggesting the possible regulatory mechanism that are involved in face aging. Conclusions: These findings, while exploratory, raise the hypothesis that ICSs may impact face aging through upregulation of ORMDL3 expression and 5-hydroxylysine metabolism and highlight the need for further pharmacological and clinical research to validate these potential effects. Full article
(This article belongs to the Section Pharmacology)
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16 pages, 2458 KiB  
Article
Evaluating TnP as a Potential Therapeutic Agent for Retinopathy in Zebrafish Models
by João Gabriel Santos Rosa, Jefferson Thiago Gonçalves Bernardo, Yolanda Álvarez, Breandán Kennedy, Carla Lima and Monica Lopes-Ferreira
Pharmaceuticals 2025, 18(6), 840; https://doi.org/10.3390/ph18060840 - 4 Jun 2025
Viewed by 586
Abstract
Background: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has [...] Read more.
Background: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish—which share significant genetic homology with humans—we investigated TnP’s effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl2)-induced hypoxia or light-induced retinal damage (LIRD). Methods: We employed two retinal injury models (CoCl2-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual–motor response testing and histological examination. Results: CoCl2 exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)’s thickness. Conclusions: Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments. Full article
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15 pages, 1483 KiB  
Review
Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges
by José Luis Lopez-Campos, Belén Muñoz-Sánchez, Marta Ferrer-Galván and Esther Quintana-Gallego
Biomolecules 2025, 15(6), 807; https://doi.org/10.3390/biom15060807 - 3 Jun 2025
Viewed by 579
Abstract
Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition classically associated with pulmonary emphysema and liver disease. However, the potential link between AATD and other respiratory diseases, particularly bronchial asthma, remains poorly understood and highly debated. This narrative review explores the current evidence [...] Read more.
Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition classically associated with pulmonary emphysema and liver disease. However, the potential link between AATD and other respiratory diseases, particularly bronchial asthma, remains poorly understood and highly debated. This narrative review explores the current evidence regarding the epidemiological, clinical, and pathophysiological relationship between AATD and asthma. Data from prevalence studies show marked variability in the frequency of AATD-associated alleles among asthma patients, ranging from 2.9% to 25.4%, suggesting either a true association or selection biases. Conversely, asthma prevalence among AATD patients also varies widely, from 1.4% to 44.6%, with higher frequencies observed in countries with long-standing national registries. However, methodological inconsistencies and a lack of standardized diagnostic criteria limit the interpretation of these findings. Current evidence is insufficient to support a direct causal role for AATD mutations in asthma development, and no clear impact of AATD on asthma severity or prognosis has been established. Furthermore, there is no conclusive evidence that augmentation therapy is beneficial in asthma patients carrying AATD mutations. Despite these uncertainties, screening for AATD in selected asthma populations—especially those with severe or atypical phenotypes—may be warranted, as recommended by major respiratory societies. Future research should focus on large, well-powered, prospective studies that evaluate the potential pathophysiological interactions between AATD and specific asthma endotypes, particularly T2-low asthma. These efforts may help clarify the relevance of AATD mutations in asthma pathogenesis and identify potential therapeutic targets. Full article
(This article belongs to the Special Issue Roles of Alpha-1 Antitrypsin in Human Health and Disease Models)
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