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PloS One 2024Allergic inflammation, which is the pathogenesis of allergic rhinitis and asthma, is associated with disruption of the airway epithelial barrier due to the effects of...
Allergic inflammation, which is the pathogenesis of allergic rhinitis and asthma, is associated with disruption of the airway epithelial barrier due to the effects of type 2 inflammatory cytokines, i.e. interleukin-4 and interleukin-13 (IL-4/13). The anti-allergic inflammatory effect of β-eudesmol (BE) on the tight junction (TJ) of the airway epithelium has not previously been reported. Herein, the barrier protective effect of BE was determined by measurement of transepithelial electrical resistance and by paracellular permeability assay in an IL-4/13-treated 16HBE14o- monolayer. Pre-treatment of BE concentration- and time- dependently inhibited IL-4/13-induced TJ barrier disruption, with the most significant effect observed at 20 μM. Cytotoxicity analyses showed that BE, either alone or in combination with IL-4/13, had no effect on cell viability. Western blot and immunofluorescence analyses showed that BE inhibited IL-4/13-induced mislocalization of TJ components, including occludin and zonula occludens-1 (ZO-1), without affecting the expression of these two proteins. In addition, the mechanism of the TJ-protective effect of BE was mediated by inhibition of IL-4/13-induced STAT6 phosphorylation, in which BE might serve as an antagonist of cytokine receptors. In silico molecular docking analysis demonstrated that BE potentially interacted with the site I pocket of the type 2 IL-4 receptor, likely at Asn-126 and Tyr-127 amino acid residues. It can therefore be concluded that BE is able to prevent IL-4/13-induced TJ disassembly by interfering with cytokine-receptor interaction, leading to suppression of STAT6-induced mislocalization of occludin and ZO-1. BE is a promising candidate for a therapeutic intervention for inflammatory airway epithelial disorders driven by IL-4/13.
Topics: Tight Junctions; Humans; Epithelial Cells; Interleukin-4; Interleukin-13; STAT6 Transcription Factor; Zonula Occludens-1 Protein; Occludin; Cell Line; Molecular Docking Simulation; Cytokines; Cell Survival
PubMed: 38687777
DOI: 10.1371/journal.pone.0302851 -
Environment International May 2024Microplastics (MPs) are plastic particles < 5 mm in diameter, of which polystyrene microplastics (PS-MPs) are representative type. The extracellular matrix (ECM)...
Microplastics (MPs) are plastic particles < 5 mm in diameter, of which polystyrene microplastics (PS-MPs) are representative type. The extracellular matrix (ECM) degradation of macrophages is associated with the development of emphysema. Additionally, circular RNAs (circRNAs) have a regulatory role in epigenetic mechanisms related to lung disease. However, the mechanisms of the ECM degradation and circRNAs in MPs-induced emphysema are still unclear. In our study, Sprague-Dawley (SD) rats were treated with 0, 0.5, 1.0 and 2.0 mg/m 100 nm PS-MPs for 90 days in an inhalation experiment. PS-MPs-exposed rats showed elevated airway resistance and pulmonary dysfunction. Lung histopathology exhibited inflammatory cell infiltration, septal thickening and alveolar dilatation. Exposure to PS-MPs was able to induce elevated levels of ECM degradation-related markers MMP9 and MMP12, as well as reduced levels of elastin in rat lung tissues. CircRNA_SMG6 is a non-coding RNA (ncRNA) with a homologous circular structure in human, rat and mouse. The expression level of circRNA_SMG6 was decreased in both rat lung tissues exposed to PS-MPs and PS-MPs-treated THP-1 cells. The luciferase reporter gene demonstrated that circRNA_SMG6 combined with miR-570-3p and co-regulated PTEN, the target gene of miR-570-3p. Moreover, overexpression of circRNA_SMG6 or inhibition of miR-570-3p attenuated PS-MPs-induced ECM degradation in THP-1 cells. Taken together, circRNA_SMG6 may have a significant function in the deterioration of emphysema caused by PS-MPs-induced macrophage ECM degradation by regulating miR-570-3p. Our findings reveal a novel mechanism of emphysema caused by PS-MPs and provide valuable information for assessing the health risks of MPs.
Topics: Animals; RNA, Circular; MicroRNAs; Rats, Sprague-Dawley; Rats; Extracellular Matrix; Microplastics; Lung; Male; Humans; Emphysema; Macrophages; Macrophages, Alveolar
PubMed: 38685156
DOI: 10.1016/j.envint.2024.108701 -
The Korean Journal of Physiology &... May 2024Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough...
Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.
PubMed: 38682171
DOI: 10.4196/kjpp.2024.28.3.229 -
Cureus Apr 2024Traumatic perforation of the tympanic membrane often occurs in Japanese patients who scratch their ears to relieve itching. Traumatic tympanic membrane perforation may...
A Successful Case Report of Epipharyngeal Abrasive Therapy (EAT) in a Patient With Sleep Apnea Syndrome and Traumatic Tympanic Membrane Perforation Caused by Chronic Epipharyngitis.
Traumatic perforation of the tympanic membrane often occurs in Japanese patients who scratch their ears to relieve itching. Traumatic tympanic membrane perforation may close spontaneously, but the perforation may remain. One of the causes of prolonged tympanic membrane perforation closure is dysfunction of the Eustachian tube. In this study, I experienced a case of chronic epipharyngitis causing ear fullness and itching, and a traumatic perforation of the tympanic membrane caused by scratching with an earpick. The patient also had sleep apnea syndrome (SAS). Treatment of chronic epipharyngitis with epipharyngeal abrasive therapy (EAT) shortened the time to perforation closure and improved SAS, suggesting that EAT affected the improvement of Eustachian tube function and airway resistance in the epipharynx.
PubMed: 38680824
DOI: 10.7759/cureus.59089 -
Journal of Virological Methods Jun 2024We established primary porcine nasal, tracheal, and bronchial epithelial cells that recapitulate the physical and functional properties of the respiratory tract and have...
We established primary porcine nasal, tracheal, and bronchial epithelial cells that recapitulate the physical and functional properties of the respiratory tract and have the ability to fully differentiate. Trans-well cultures demonstrated increased transepithelial electrical resistance over time the presence of tight junctions as demonstrated by immunohistochemistry. The nasal, tracheal, and bronchial epithelial cells developed cilia, secreted mucus, and expressed sialic acids on surface glycoproteins, the latter which are required for influenza A virus infection. Swine influenza viruses were shown to replicate efficiently in the primary epithelial cell cultures, supporting the use of these culture models to assess swine influenza and other virus infection. Primary porcine nasal, tracheal, and bronchial epithelial cell culture models enable assessment of emerging and novel influenza viruses for pandemic potential as well as mechanistic studies to understand mechanisms of infection, reassortment, and generation of novel virus. As swine are susceptible to infection with multiple viral and bacterial respiratory pathogens, these primary airway cell models may enable study of the cellular response to infection by pathogens associated with Porcine Respiratory Disease Complex.
Topics: Animals; Swine; Epithelial Cells; Trachea; Bronchi; Cells, Cultured; Cell Culture Techniques; Influenza A virus; Virus Replication
PubMed: 38679164
DOI: 10.1016/j.jviromet.2024.114943 -
Veterinary Anaesthesia and Analgesia 2024To evaluate the effect of increased respiratory system resistance (R) on dynamic compliance (C) assessed by the NM3 monitor (C) and the E-CAiOV module (C).
OBJECTIVE
To evaluate the effect of increased respiratory system resistance (R) on dynamic compliance (C) assessed by the NM3 monitor (C) and the E-CAiOV module (C).
STUDY DESIGN
Prospective laboratory study.
METHODS
A training test lung (TTL) simulated the mechanical ventilation of a mammal with 50 and 300 mL tidal volumes in three conditions of R [normal (R), moderately increased (R) and severely increased (R)] and a wide range of clinically relevant C. Simulations at increased R were paired with simulations at R with the same static compliance for comparisons. Pearson's correlation coefficient and concordance correlation coefficient between the measurements at R with the ones with increased R were calculated. Bland-Altman plots were also used to evaluate the agreement of C and C at R (control values) with their paired values at R and R. Relative bias and limits of agreement (LOAs) were calculated and LOAs larger than 30% were considered unacceptable. Trending ability of C and C were evaluated by polar plots. Values of p < 0.05 were considered significant.
RESULTS
The effect of increased R was more pronounced for C than for C. Unacceptable agreement was only observed in C at R in the 300 mL simulation (bias = -18.3% and lower LOA = -45%). For C, agreement was unacceptable for all tested R in both simulations, being the worst at R in the 300 mL simulation (bias = -54.7% and lower LOA = -100.2%). Both levels of increased R caused poor trending ability for C, whereas the same effect was only observed for C at R.
CONCLUSIONS AND CLINICAL RELEVANCE
In the presence of increased R, C estimated by the NM3 monitor presented better capability to distinguish between changes in R from changes in respiratory system compliance.
Topics: Animals; Respiration, Artificial; Lung Compliance; Lung; Prospective Studies; Airway Resistance; Monitoring, Physiologic; Tidal Volume
PubMed: 38677969
DOI: 10.1016/j.vaa.2024.03.003 -
Journal of Clinical Medicine Apr 2024Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and...
Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) ( < 0.001 for all). : Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed "Quiet Asthma".
PubMed: 38673593
DOI: 10.3390/jcm13082320 -
American Society of Clinical Oncology... Jun 2024This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non-small cell lung cancer. We also address... (Review)
Review
This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non-small cell lung cancer. We also address pertinent clinical decision-making queries encountered in everyday practice, such as the optimal treatment strategy for PD-L1-high patients, predictive factors for response to immune checkpoint inhibitors (ICI) both in terms of patient and cancer characteristics, the potential benefits of dual checkpoint blockade, and the unresolved issue of safe discontinuation strategies for long-term responders. Around one in five patients falls into this latter category while the majority develop either primary or acquired resistance to ICI-based first-line therapy, necessitating effective subsequent lines of treatment. Docetaxel, with or without combination of antiangiogenic agents, serves as the backbone of treatment, although evidence in the post-ICI setting is limited. Given that an inflamed tumor microenvironment (TME) is crucial for ICI responses, targeting the TME in cases of acquired resistance alongside continued ICI administration appears rational, although clinical trials so far have failed to confirm this hypothesis. Antibody-drug conjugates have emerged as a promising treatment modality, offering the potential for reduced toxicity and improved efficacy by targeting specific cancer antigens. Moreover, several chemotherapy-free approaches are currently under investigation for treatment-naïve patients, including alternative ICI and drugs targeting epitopes on both cancer and immune cells.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Tumor Microenvironment; Neoplasm Metastasis; Molecular Targeted Therapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38669613
DOI: 10.1200/EDBK_432524 -
Pathogens (Basel, Switzerland) Apr 2024Bovine respiratory disease (BRD) is the leading cause of mortality and antimicrobial drug (AMD) use in weaned dairy heifers. Limited information is available regarding...
Bovine respiratory disease (BRD) is the leading cause of mortality and antimicrobial drug (AMD) use in weaned dairy heifers. Limited information is available regarding antimicrobial resistance (AMR) in respiratory bacteria in this population. This study determined AMR gene presence in 326 respiratory isolates (, , and ) from weaned dairy heifers using whole genome sequencing. Concordance between AMR genotype and phenotype was determined. Twenty-six AMR genes for 8 broad classes of AMD were identified. The most prevalent, medically important AMD classes used in calf rearing, to which these genes predict AMR among study isolates were tetracycline (95%), aminoglycoside (94%), sulfonamide (94%), beta-lactam (77%), phenicol (50%), and macrolide (44%). The co-occurrence of AMR genes within an isolate was common; the largest cluster of gene co-occurrence encodes AMR to phenicol, macrolide, elfamycin, β-lactam (cephalosporin, penam cephamycin), aminoglycoside, tetracycline, and sulfonamide class AMD. Concordance between genotype and phenotype varied (Matthew's Correlation Coefficient ranged from -0.57 to 1) by bacterial species, gene, and AMD tested, and was particularly poor for fluoroquinolones (no AMR genes detected) and ceftiofur (no phenotypic AMR classified while AMR genes present). These findings suggest a high genetic potential for AMR in weaned dairy heifers; preventing BRD and decreasing AMD reliance may be important in this population.
PubMed: 38668255
DOI: 10.3390/pathogens13040300 -
Respiratory Research Apr 2024Computer Aided Lung Sound Analysis (CALSA) aims to overcome limitations associated with standard lung auscultation by removing the subjective component and allowing...
BACKGROUND
Computer Aided Lung Sound Analysis (CALSA) aims to overcome limitations associated with standard lung auscultation by removing the subjective component and allowing quantification of sound characteristics. In this proof-of-concept study, a novel automated approach was evaluated in real patient data by comparing lung sound characteristics to structural and functional imaging biomarkers.
METHODS
Patients with cystic fibrosis (CF) aged > 5y were recruited in a prospective cross-sectional study. CT scans were analyzed by the CF-CT scoring method and Functional Respiratory Imaging (FRI). A digital stethoscope was used to record lung sounds at six chest locations. Following sound characteristics were determined: expiration-to-inspiration (E/I) signal power ratios within different frequency ranges, number of crackles per respiratory phase and wheeze parameters. Linear mixed-effects models were computed to relate CALSA parameters to imaging biomarkers on a lobar level.
RESULTS
222 recordings from 25 CF patients were included. Significant associations were found between E/I ratios and structural abnormalities, of which the ratio between 200 and 400 Hz appeared to be most clinically relevant due to its relation with bronchiectasis, mucus plugging, bronchial wall thickening and air trapping on CT. The number of crackles was also associated with multiple structural abnormalities as well as regional airway resistance determined by FRI. Wheeze parameters were not considered in the statistical analysis, since wheezing was detected in only one recording.
CONCLUSIONS
The present study is the first to investigate associations between auscultatory findings and imaging biomarkers, which are considered the gold standard to evaluate the respiratory system. Despite the exploratory nature of this study, the results showed various meaningful associations that highlight the potential value of automated CALSA as a novel non-invasive outcome measure in future research and clinical practice.
Topics: Humans; Cross-Sectional Studies; Male; Female; Respiratory Sounds; Prospective Studies; Adult; Cystic Fibrosis; Young Adult; Biomarkers; Adolescent; Auscultation; Tomography, X-Ray Computed; Lung; Child; Proof of Concept Study; Diagnosis, Computer-Assisted; Middle Aged
PubMed: 38658980
DOI: 10.1186/s12931-024-02810-5