Mucus Hypersecretion Research Articles

Qufeng Xuanbi Formula inhibited benzo[a]pyrene-induced aggravated asthma airway mucus secretion by AhR/ROS/ERK pathway

Ethnopharmacological relevanceExcessive secretion of airway mucus may be an important pathological factor of air pollution-induced acute asthma attacks. Treatment of airway mucus hypersecretion improves asthma aggravated by air pollutants. Qufeng Xuanbi Formula (QFXBF) has been used to treat asthma for more than 30 years. However, whether QFXBF inhibits asthmatic mucus secretion exacerbated by air pollutants has not yet been established. Aim of the studyThis study aimed to evaluate the effect of QFXBF on airway mucus secretion and the mechanism of action in an air pollutant benzo[a]pyrene (BaP)-induced mouse model of aggravated asthma. Materials and methodsOvalbumin (OVA) and BaP co-exposure were used to establish the aggravated asthma model. The average enhanced pause (Penh), serum OVA-specific IgE, and changes in lung histopathology were determined. 16HBE cells exposed to BaP, treatment with QFXBF, arylhydrocarbon receptor (AhR) signal antagonist SR1, reactive oxygen species (ROS) antagonist NAC, or extracellular signal-regulated kinase (ERK1/2) signal antagonist U0126 were established to investigate the effect of QFXBF on BaP-induced mucus secretion and its target. The mRNA and protein expression levels of MUC5AC in the lung tissue and 16HBE cells were examined. We also studied the effect of QFXBF on ROS production. Finally, the protein expression of AhR, phospho-extracellular signal-regulated kinases (p-ERK1/2), and ERK1/2 in 16HBE cells and lung tissues was determined by western blotting. ResultsAdministration of QFXBF significantly alleviated the pathological symptoms, including Penh, serum OVA-specific IgE, and changes in lung histopathology in a BaP-induced mouse model of aggravated asthma. QFXBF inhibited MUC5AC expression in asthmatic mice and 16HBE cells exposed to BaP. ROS production, AhR expression, and ERK1/2 phosphorylation were significantly increased in BaP-induced asthmatic mice and 16HBE cells. Signaling pathway inhibitors StemRegenin 1 (SR1), NAC, and U0126 significantly inhibitedBaP-induced MUC5AC expression in 16HBE cells. SR1 reversed Bap-induced ROS production and ERK activation, and NAC inhibited Bap-induced ERK activation. In addition, QFXBF regulated AhR signaling, inhibited ROS production, reversed ERK activation, and downregulated mucus secretion to improve asthma aggravated by air pollutant BaP. ConclusionsQFXBF can ameliorate mucus secretion in BaP-induced aggravated asthmatic mice and 16HBE cells, and the specific mechanism may be related to the inhibition of the AhR/ROS/ERK signaling pathway.

CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway.

The downregulation of adhesion molecule catenin alpha-like 1 (CTNNAL1) in airway epithelial cells of asthma patients and house dust mite (HDM)-induced asthma animal models was illustrated in our previous study. It is assumed to contribute to airway inflammation and mucus hypersecretion. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. CTNNAL1-silenced female mice exhibit a decreased level of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated and ATP-gated Cl - channel that correlates with mucus hypersecretion. Our previous study demonstrated that ROCK1 expression decreases but ROCK2 expression increases in the lungs of a CTNNAL1-silenced mouse model. Inhibition of ROCK1 leads to a reduction in CFTR expression in CTNNAL1-overexpressing and CTNNAL1-silenced human bronchial epithelial (HBE) cells. It has been reported that ROCK1 is a downstream target of RhoA and that activation of RhoA increases CFTR expression after CTNNAL1 deficiency in vitro and in vivo. The above results indicate that CTNNAL1 regulates CFTR expression through the ROCK1 pathway. In addition, the expression of CFTR-associated ligand (CAL) is increased after CTNNAL1 silencing, and immunoprecipitation results confirm the interaction between ROCK1 and CAL. Inhibition of CAL does not influence ROCK1 expression but increases CFTR expression in CTNNAL1-silenced HBE cells. These data suggest that CTNNAL1 deficiency decreases CFTR expression in the HDM-induced asthma mouse model through the ROCK1-CAL signaling pathway.

Sestrin2/Keap1/Nrf2 pathway regulates mucus hypersecretion in pulmonary epithelium induced by traffic-related PM2.5 and water-soluble extracts

The involvement of fine particulate matter (PM2.5) exposure in the progression of asthma has been extensively discussed in epidemiological and experimental evidence, which aroused widespread attention. Asthma is characterized by mucus hypersecretion. This study investigates the underlying toxic mechanism of traffic-related PM2.5 (TRPM2.5) and water-soluble extracts (WSE) on mucus hypersecretion in the lungs of rats with asthma and 16HBE cells. The ovalbumin-induced rats were administrated by instillation of TRPM2.5 and WSE in the trachea once three days for eight times. The results showed that TRPM2.5 and WSE had an adverse impact on mucus secretion. Specifically, conspicuous mucus stains and increased goblet cells in the bronchial epithelium by PAS staining were found in lung tissues of rats with asthma; MUC5AC gene and protein expression levels in lung tissues of rats with asthma and 16HBE cells were elevated. In addition, TRPM2.5 and WSE triggered oxidative damage via upregulation of malondialdehyde and myeloperoxidase as well as activation of the Sestrin2/Keap1/Nrf2 signaling pathway. Conversely, the knockdown of Sestrin2 effectively inhibited TRPM2.5 and WSE-induced mucus hypersecretion, oxidative stress, and Keap1/Nrf2 signaling pathway and its downstream target gene NQO1. Collectively, it was demonstrated that TRPM2.5 and WSE induced mucus hypersecretion mediated by the Sestrin2/Keap1/Nrf2 pathway.

P22-12: Mucus hyper secretion in Bronchus-on-a-Chip as the airway remodeling indication

P22-12: Mucus hyper secretion in Bronchus-on-a-Chip as the airway remodeling indication

Ciliary dyskinesia in severe asthma is not affected by chronic mucus hypersecretion.

Chronic mucus hypersecretion (CMH) is linked to increased asthma severity. Ciliary dyskinesia is present in severe asthma but CMH was not associated with a worse ciliary dysfunction, suggesting another mechanism to explain chronic cough and phlegm. https://bit.ly/3JNUgGr.

Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and Their Roles in the Progression of Respiratory Diseases.

The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both periodontal diseases and respiratory diseases show high prevalence worldwide and have a marked influence on the quality of life for the patients. Accumulating studies are establishing a compelling association between periodontal diseases and respiratory diseases. Here, in this review, we specifically focus on the key periodontal pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum and dissect their roles in the onset and course of respiratory diseases, mainly pneumonia, chronic obstructive pulmonary disease, lung cancer, and asthma. The mechanistic underpinnings and molecular processes on how P. gingivalis and F. nucleatum contribute to the progression of related respiratory diseases are further summarized and analyzed, including: induction of mucus hypersecretion and chronic airway inflammation; cytotoxic effects to disrupt the morphology and function of respiratory epithelial cells; synergistic pathogenic effects with respiratory pathogens like Streptococcus pneumoniae and Pseudomonas aeruginosa. By delving into the complex relationship to periodontal diseases and periodontopathogens, this review helps unearth novel insights into the etiopathogenesis of respiratory diseases and inspires the development of potential therapeutic avenues and preventive strategies.

Caveolin-1-derived peptide attenuates cigarette smoke-induced airway and alveolar epithelial injury.

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease with no effective treatment that can reduce mortality or slow the disease progression. COPD is the third leading cause of global death and is characterized by airflow limitations due to chronic bronchitis and alveolar damage/emphysema. Chronic cigarette smoke (CS) exposure damages airway and alveolar epithelium and remains a major risk factor for the pathogenesis of COPD. We found that the expression of caveolin-1, a tumor suppressor protein; p53; and plasminogen activator inhibitor-1 (PAI-1), one of the downstream targets of p53, was markedly increased in airway epithelial cells (AECs) as well as in type II alveolar epithelial (AT2) cells from the lungs of patients with COPD or wild-type mice with CS-induced lung injury (CS-LI). Moreover, p53- and PAI-1-deficient mice resisted CS-LI. Furthermore, treatment of AECs, AT2 cells, or lung tissue slices from patients with COPD or mice with CS-LI with a seven amino acid caveolin-1 scaffolding domain peptide (CSP7) reduced mucus hypersecretion in AECs and improved AT2 cell viability. Notably, induction of PAI-1 expression via increased caveolin-1 and p53 contributed to mucous cell metaplasia and mucus hypersecretion in AECs, and reduced AT2 viability, due to increased senescence and apoptosis, which was abrogated by CSP7. In addition, treatment of wild-type mice having CS-LI with CSP7 by intraperitoneal injection or nebulization via airways attenuated mucus hypersecretion, alveolar injury, and significantly improved lung function. This study validates the potential therapeutic role of CSP7 for treating CS-LI and COPD. NEW & NOTEWORTHY Chronic cigarette smoke (CS) exposure remains a major risk factor for the pathogenesis of COPD, a debilitating disease with no effective treatment. Increased caveolin-1 mediated induction of p53 and downstream plasminogen activator inhibitor-1 (PAI-1) expression contributes to CS-induced airway mucus hypersecretion and alveolar wall damage. This is reversed by caveolin-1 scaffolding domain peptide (CSP7) in preclinical models, suggesting the therapeutic potential of CSP7 for treating CS-induced lung injury (CS-LI) and COPD.

Therapeutic Effect of Atorvastatin on Interleukin-13- Induced Lung Pathology

PPurpose: Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on IL-13-induced lung pathology through the modulation of macrophages. Methods: Atorvastatin (40 mg/ kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, the number of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar macrophage (AM) cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed. Results: Significant reduction in total leukocytes and alleviation of AHR were observed with the administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P < 0.05). Atorvastatin administration resulted in the upregulation of IL-10 in the lungs of IL-13 TG mice (P < 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P < 0.05). M2 macrophage markers were decreased, while the M1 macrophage marker was increased upon atorvastatin treatment (P < 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P < 0.05). Conclusion: The results of this study reveal the potential of atorvastatin as an effective anti-asthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.

Possible role of HE4 level elevation in the pathogenesis of TH2-high asthma

Objectives As a heterogeneous disease, asthma is characterized by airway hyperresponsiveness, airway inflammation, and airway mucus hypersecretion. According to the pathological changes, symptoms, preventive and treatment methods, asthma can be divided into TH2-high and TH2-low asthma. We show that the expression of the tumor biomarker human epididymis protein 4 (HE4) was significantly increased in TH2-high asthma group, while there was no marked difference in its expression between TH2-low asthma and healthy control groups. HE4 levels were significantly increased in plasma, induced sputum, and alveolar lavage fluid (BALF) samples and airway epithelial cells from TH2-high asthma group, showing that HE4 has a possible role in the pathogenesis of TH2-high asthma. Methods Using RT–qPCR, ELISA, Western blot (WB), and immunohistochemistry, we assessed differences in HE4 expression in plasma, induced sputum, BALF, and airway epithelial cells among patients with the TH2-related asthma subtypes and healthy controls. To explore the role of HE4 in TH2-high asthma, we conducted a correlation analysis between HE4 levels in plasma, induced sputum, BALF, and airway epithelial cells and multiple indicators of airway eosinophilic inflammation, airway mucus secretion, and airway remodeling. Conclusion We found for the first time that HE4 was differentially expressed in the TH2-related asthma subtypes. In TH2-high asthma, HE4 levels were markedly elevated in airway epithelial cells, plasma, induced sputum, and BALF. HE4 may play an important role in various pathogenic mechanisms of asthma, such as airway eosinophilic inflammation, airway mucus secretion, and airway remodeling. HE4 in plasma may be a clinically biomarker for differentiating TH2-related asthma subtypes.

Chemical constituents from the flowers of Inula japonica and their anti-inflammatory activity

Ethnopharmacological relevanceThe flowers of Inula japonica (Inulae Flos) can be used to treat cough and asthma and remove phlegm in traditional Chinese medicine (TCM). Aim of the studyOur research aimed to obtain active components with the inhibition of inflammation and MUC5AC production to alleviate asthma symptoms from I. japonica. Materials and methodsThese compounds were separated from the MeOH extract of Inulae Flos by column chromatography over silica gel, AB-8 macroporous resin column, MPLC, and semipreparative HPLC. Their structures were elucidated by detailed spectroscopic data analysis, ECD calculations, and chemical methods. NO production was determined to evaluate anti-inflammatory activity in RAW 264.7 cells. The expression of MUC5AC, IL-1β, and IL-4 were measured in NCI–H292 cells by qRT-PCR. The anti-asthma activity assessments in vivo were performed through H & E and PAS staining, pulmonary function analysis, and cytokines determination by qRT-PCR or ELISA. The expression levels of PI3K, p-PI3K, AKT, p-AKT, MEK, p-MKE, ERK, p-MEK, and IL-1β were analyzed through western blotting. ResultsOne undescribed 1,10-seco-eudesmanolide derivative (1), two previously unreported 1,10-seco-eudesmanolide glycosides (2 and 3), and thirty-two known compounds (4–35) were obtained from Inulae Flos. Compound 11 had the most inhibitory effect against LPS-induced NO production in RAW 264.7 murine macrophages. Meanwhile, compound 11 also attenuated the increase in MUC5AC, IL-1β, and IL-4 mRNA expression in NCI–H292 cells. The results of the animal experiment confirmed that compound 11 significantly ameliorated OVA-induced asthma in a murine model of allergic asthma demonstrated by elevated pulmonary function, reduced inflammatory cell infiltration and mucus production. In addition, compound 11 significantly inhibited the levels of OVA-specific IgE in serum, of IL-4 and IL-6 in BALF, and of MUC5AC, IL-1β , IL-4, IL-5, IL-6 and IL-13 in lung tissue. Finally, compound 11 suppressed PI3K/AKT/MEK/ERK signaling pathway in lung tissue of mice. ConclusionThis study indicated that compound 11 might be a potential therapeutic candidate ameliorating airway inflammation and mucus hypersecretion via PI3K/AKT/MEK/ERK signaling pathway in allergic asthma.

Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Metabolism and Microstructure of the Small Intestine Wall in Patients With Colorectal Cancer

RELEVANCE In patients with colorectal cancer (CRC), the normal small intestine, located outside the pathological focus, undergoes changes that may be the cause of digestive dysfunction after radical surgery to remove the tumor.The assessment of metabolic and microstructural changes in the ileum mucosa in patients with colorectal cancer is necessary to correct the algorithms of postoperative therapy and enteral nutrition. Modern means of optical bioimaging are potentially capable of solving this complex diagnostic problem.AIM OF STUDY To study the features of metabolism and morphological structure of the wall of a conditionally normal small intestine in the mucosa in patients with stage 1–3 CRC using macro- FLIM and optical coherence tomography (OCT).MATERIAL AND METHODS The object of the study was the wall of the ileum (66 samples) from the mucosal side of patients with histologically confirmed CRC stages 1–3 with tumor location in the right sections of the colon. Eight samples were obtained from patients with stage 1 CRC, 38 samples were obtained from patients with stage 2 and 20 samples were obtained from patients with stage 3 tumor. The volume of surgical intervention is right-sided hemicolectomy with total mesocolonectomy, CME (D2 lymph node dissection). Fresh tissue samples were examined using fluorescent lifetime macroimaging (macro-FLIM ) and OCT, followed by histological analysis of the material.RESULTS According to a histological study in the small intestine of patients with stage 1 CRC, the mucosa is covered with a normal single-layer prismatic border epithelium. In the intestine samples of patients with stage 2 CRC, mucus hypersecretion with areas of fibrosis and vascular congestion was observed. At the 3rd stage of CRC, the mucous membrane of the small intestine was loose, with local thickenings, areas of fibrosis with severe leukostasis, and foci of atrophy. None of the samples showed histological signs of a malignant tumor.According to OCT data, in the mucous membrane of the small intestine in patients with the 1st and 2nd stages of CRC, the contours of the villi and, partially, the crypts were well visualized. The structure of the villi was smooth, not coarse, and the shape was regular. In patients with stage 3 CRC, the contours of the crypts and villi were indistinct. There were no differences in the OCT picture between histologic preparations in the 1st and 2nd stages of CRC: the structure of the villi of the small intestine was clear, the shape was unchanged. According to FLIM data, statistically significant differences were revealed in the mean fluorescence lifetime values of reduced nicotinamide dinucleotide (phosphate) NAD(P)H (τm) between 2nd and 3rd (p=0.031), 1st and 3rd (p=0.018) by CRC stages. At the 1st stage of CRC τm was 1.61 [1.30; 2.02] ns, at the 2nd stage 1.50 [1.36; 1.73] ns, at the 3rd stage 1.37 [1.22; 1.51] ns. The FLIM results suggest an increase in the role of glycolysis in enterocyte energy metabolism along with progression of the CRC stage.CONCLUSION In patients with cancer of the right colon, lesions of the microstructure of the mucous membrane were revealed in the ileum not affected by the malignancy. At the same time, the severity of microstructural disorders in the wall of the small intestine is associated with the stage of tumor development in the colon. Bioimaging technologies, namely, methods of optical coherence tomography and fluorescence lifetime macroimaging, made it possible to objectively display microstructural and metabolic disorders in the ileum wall. The data of optical colorectal tomography demonstrated differences in the structural picture of the intestinal villi in patients with stages 1–2 and 3 of colorectal cancer. Results of fluorescence lifetime macroimaging of the metabolic cofactor nicotinamide dinucleotide (phosphate) confirmed an increase in the role of glycolysis in the energy metabolism of enterocytes along with an increase in the stage of colorectal cancer. The identified disorders in the state of the small intestine develop in patients with colorectal cancer before surgery and are highly likely to be an important pathogenetic link of malabsorption in the postoperative period. If the hypothesis is confirmed, the developed algorithm for the complex diagnosis of microstructural and metabolic disorders in tissues will expand the possibilities for the rehabilitation of patients with cancer of the right colon.

The Anti-inflammatory Effects of Hydrogen-Rich Water Acts in a Volume-Dependent Manner on Rats’ Lungs Exposed to Cigarette Smoke

&lt;em&gt;Cigarette smoke can activate various ROS-sensitive signaling pathways in the lungs, triggering airway inflammation and leading to mucus hypersecretion. Meanwhile, hydrogen has shown anti-inflammatory activity in various injury models. This study aims to determine the anti-inflammatory effect of hydrogen-rich water on lungs exposed to cigarette smoke in rats. Male wistar rats were divided into four groups randomly (n=5), namely CI group (given aquades + exposed to free air), CII group (given aquades + exposed to cigarette smoke), HI group (given HRW 5 mL once a day + exposed to cigarette smoke), and HII group (given HRW 5 mL twice a day + exposed to cigarette smoke). HRW/aquades was administered orally 30 minutes before cigarette smoke exposure. Exposure to cigarette smoke lasts about 15-25 minutes with 5 cigarettes/day for 28 days. Subsequently, we examine the levels of lung NF-kB p65 using the ELISA method and perform pulmonary histopathological examination. The results showed that the administration of HRW reduced the levels of NF-κB p65 induced by cigarette smoke exposure, which is significant in the HII group (p&amp;lt;0.01). From the histopathological examination, administration of HRW significantly reduced the degree of lung inflammation caused by cigarette smoke exposure in the HI and HII group (p&amp;lt;0.05).&lt;/em&gt;

TNF-α and MMPs mediated mucus hypersecretion induced by cigarette smoke: An in vitro study

Cigarette smoke is one of the leading causes of oxidative stress due to high levels of free radicals, which in turn leads to the degradation of alveolar cell walls and development of emphysema. Cigarette smoking has been linked to chronic bronchitis, Chronic Obstructive Pulmonary Disease (COPD) and lung cancer as well. The aim of the present study was to observe the effect of cigarette smoke extract (CSE) on TNF-α and MMPs mediated mucus hypersecretion in A549 cell line. The MTT experiments showed that CSE caused a dose-dependent decline in the level of viability of A549 cells. In addition, AO/PI and Mitotracker Red staining assays demonstrated that CSE caused the A549 cells to undergo apoptosis. This was determined by observing the reduction in mitochondrial membrane potential. CSE was found to be responsible for the formation of intracellular ROS, which was observed by DCFDA staining through fluorescence microscopy. Approximately 65% migration rate was decreased in 20% CSE exposed cells. CSE exposure led to the significantly increased mRNA levels of TNF-α, MMP-7, and MMP-12, in comparison to the control cells. Additionally, the expression of MUC5AC and MUC5B was provoked by CSE as well. Human epithelial cells are stimulated by TNF-α and MMPs secreted mucus, as shown by expression of MUC5AC and MUC5B. CSE could induce mucus in lungs through TNF-α and MMPs mediated pathways.

Nootkatone attenuates airway inflammation in asthmatic mice through repressing ROS-induced NLRP3 inflammasome activation.

Nootkatone (NKT) exhibits potential pharmacological activities including anti-oxidation and anti-inflammation. Nevertheless, little is known about the roles of NKT in asthmatic airway inflammation. In the study, mice were sensitized and challenged with ovalbumin (OVA) to establish experimental allergic asthma model. After treatment with NKT, lung tissues, peripheral blood, and bronchoalveolar lavage fluid (BALF) were collected to assess inflammatory cytokines, oxidative stress, and pathological alternations. The effects of NKT on regulating reactive oxygen species (ROS)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation was assessed in IL-13-treated BEAS-2B cell model. We found that NKT treatment decreased the production of Th2 inflammatory cytokines (IL-4, IL-5, and IL-13) in BALF and IgE levels in serum, and alleviated inflammatory cell penetration, goblet cell proliferation, collagen accumulation, and mucus hypersecretion in lung tissues. NKT treatment mitigated oxidative stress and NLRP3 inflammasome activation in asthmatic mice. IL-13 treatment induced oxidative stress and NLRP3-mediated pyroptosis in BEAS-2B bronchial epithelial cells, whereas these effects were blocked by NKT. NKT protected against airway remodeling, as indicated by decreased epithelial-mesenchymal transition. Taken together, these results demonstrate that NKT mitigates asthmatic airway inflammation by inhibiting ROS-triggered NLRP3 activation and may be a potential agent for treating asthma.

Inflammatory and antiviral responses to influenza A virus infection are dysregulated in pregnant mice with allergic airway disease.

Influenza A virus (IAV) infections are increased during pregnancy especially with asthma as a comorbidity, leading to asthma exacerbations, secondary bacterial infections, intensive care unit admissions, and mortality. We aimed to define the processes involved in increased susceptibility and severity of IAV infections during pregnancy, especially with asthma. We sensitized mice to house dust mite (HDM), induced pregnancy, and challenged with HDM to induce allergic airway disease (AAD). At midpregnancy, we induced IAV infection. We assessed viral titers, airway inflammation, lung antiviral responses, mucus hypersecretion, and airway hyperresponsiveness (AHR). During early IAV infection, pregnant mice with AAD had increased mRNA expression of the inflammatory markers Il13 and IL17 and reduced mRNA expression of the neutrophil chemoattractant marker Kc. These mice had increased mucous hyperplasia and increased AHR. miR155, miR574, miR223, and miR1187 were also reduced during early infection, as was mRNA expression of the antiviral β-defensins, Bd1, Bd2, and Spd and IFNs, Ifnα, Ifnβ, and Ifnλ. During late infection, Il17 was still increased as was eosinophil infiltration in the lungs. mRNA expression of Kc was reduced, as was neutrophil infiltration and mRNA expression of the antiviral markers Ifnβ, Ifnλ, and Ifnγ and Ip10, Tlr3, Tlr9, Pkr, and Mx1. Mucous hyperplasia was still significantly increased as was AHR. Early phase IAV infection in pregnancy with asthma heightens underlying inflammatory asthmatic phenotype and reduces antiviral responses.NEW & NOTEWORTHY Influenza A virus (IAV) infection during pregnancy with asthma is a major health concern leading to increased morbidity for both mother and baby. Using murine models, we show that IAV infection in pregnancy with allergic airway disease is associated with impaired global antiviral and antimicrobial responses, increased lung inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). Targeting specific β-defensins or microRNAs (miRNAs) may prove useful in future treatments for IAV infection during pregnancy.

Unleashing the Power of IL-17: A Promising Frontier in Chronic Obstructive Pulmonary Disease (COPD) Treatment.

Chronic obstructive pulmonary disease (COPD) is a pulmonary ailment that is both degenerative and incapacitating, with a global prevalence affecting millions. Despite notable progress in treatment methodologies, there is still a critical requirement for innovative therapeutic interventions. The pathogenesis of COPD has recently seen a significant focus on the role of interleukin 17 (IL-17), a pro-inflammatory cytokine. This review investigates the potential of IL-17 targeting as a viable therapeutic approach for treating COPD. The literature indicates a complex correlation between IL-17 and COPD. Research has indicated that IL-17 plays a role in the manifestation of airway inflammation, remodeling, and mucus hypersecretion, considered characteristic attributes of COPD. Elevated levels of IL-17 have been observed in the lungs of individuals with COPD, indicating its potential as a therapeutic target for intervention. Furthermore, preclinical studies utilizing animal models of COPD have demonstrated the efficacy of anti-IL-17 antibodies in reducing airway inflammation and remodeling. Comprehending the mechanical principles that underlie IL-17 signaling in COPD is imperative for advancing focused, therapeutic interventions. Activating diverse signaling pathways, such as the β-catenin and Act 1 adaptor protein (ACT 1) mediated pathways, is a crucial aspect of COPD pathogenesis triggered by IL-17. As a result, the suppression of IL-17 signaling has exhibited encouraging outcomes in mitigating pulmonary hypertension induced by hypoxia and interrupting the signaling mediated by ACT 1. Notwithstanding these promising discoveries, additional investigation is required to comprehensively explain the function of IL-17 in COPD and its viability as a target for therapy. The efficacy and safety of biological treatments that target IL-17 in COPD patients necessitate thorough investigation despite their initial positive outcomes. Furthermore, identifying appropriate patient subpopulations that would benefit most from IL-17-targeted therapies and optimizing treatment protocols are binding domains for future investigation. The current review presents a persuasive case for the imperative requirement of an additional investigation into the targeting of IL-17 for COPD management. Through a comprehensive analysis of the complex relationship between IL-17 and COPD pathogenesis, novel therapeutic avenues can be explored, potentially transforming the approach to managing this incapacitating condition. As we explore this novel domain, the possibility of pioneering therapies aimed at IL-17 presents a ray of optimism for the multitudes of individuals afflicted with the onerous consequences of COPD.

Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy

Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n= 30), subcutaneous immunotherapy (SCIT) (n= 27), or sublingual immunotherapy (SLIT) (n= 27) and were then followed for 1 additional year. We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response. We used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. ClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16. SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response. Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT.

Sobrerol: New Perspectives to Manage Patients with Frequent Respiratory Infections.

Respiratory tract infections (RTIs) are usually characterized by mucus hypersecretion. This condition may worsen and prolong symptoms and signs. For this reason, reducing mucus production and improving mucus removal represent relevant aspects of managing patients with RTIs. In this regard, mucoactive drugs may be effective. Mucoactive agents constitute a large class of compounds characterized by different mechanisms of action. Sobrerol is a monoterpene able to fluidify mucus, increase mucociliary clearance, and exert antioxidant activity. Sobrerol is available in various formulations (granules, syrup, nebulized, and suppository). Sobrerol has been on the market for over 50 years. Therefore, the present article revised the evidence concerning this compound and proposed new possible strategies. The literature analysis showed that several studies investigated the efficacy and safety of sobrerol in acute and chronic RTIs characterized by mucus hyperproduction. Seven pediatric studies have been conducted with favorable outcomes. However, the regulatory agencies recently reduced the treatment duration to three days. Therefore, a future study will test the hypothesis that a combination of oral and topical sobrerol could benefit children and adults with frequent respiratory tract infections. The rationale of this new approach is based on the concept that mucus accumulation could be a risk factor for increased susceptibility to infections.

Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.

Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.