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Background: Mucin family members have been reported to be widely expressed in gastric carcinoma with diverse functions. Several important mucins exert the function of tumorigenesis or progression in gastric cancer (GC). Here, we conduct this meta-analysis to evaluate the association between mucin expression and clinicopathological features in GC. Methods: Literature searches were performed in PubMed, Embase, The Cochrane Library, and ISI Web of Science, and, finally, 28 studies met our criteria. Odds ratios or hazard ratios with 95% confidence intervals were calculated to evaluate the effect quantity. We analyzed the expression of MUC1, MUC2, MUC5AC, and MUC6 and their clinicopathological characteristics separately at the same time. Results: Twenty-eight studies that contain 4,603 patients were included in our meta-analysis. MUC1 was associated with gender, Lauren classification, depth of tumor invasion, TNM, vascular invasion, lymph metastasis, and lymphatic invasion, WHO grade, as well as the 5-year survival rate. MUC2 was significantly correlated with lymphatic invasion and WHO grade. MUC5AC was highly positive in gender, depth of tumor invasion, WHO grade, TNM, lymph metastasis, and lymphatic invasion. Moreover, cases with decreased MUC5AC expression were correlated with less 5-year survival. MUC6 was only related with lymphatic invasion. Conclusion: Our meta-analysis showed that MUC1 and MUC5AC had prognostic value in GC detected by immunohistochemistry. MUC1 and MUC5AC were also associated with some other significant clinicopathological parameters. Moreover, MUC2 and MUC6 also exert their influence in lymphatic invasion. However, further enlarged study awaits to verify our conclusion to deeply explore the role of mucin family members in GC. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionAsthma is one of the severe respiratory diseases and affects the health of people globally. Animal studies have found that the mucin 5ac (Muc5ac) levels in the lung are associated with asthma. This paper aimed to systematically evaluate the relationship between Muc5ac levels in lung and asthma by extracting relevant data from animal experiments.Literatures published before September 2022 in PubMed, Web of Science, Embase and Cochrane databases were collected. Literatures screening and data extraction were performed according to the criteria and the risks of bias were assessed for the included literatures according to the SYRCLE tool. Type 2 inflammatory asthma model was applied in this paper. Meta-analysis was performed using Stata 16.0 software.A total of 40 publications containing 347 control mice and 337 mice with asthma were included in this study. Meta-analysis results showed the levels of Muc5ac in BALF of mice in asthma group were significantly higher than that in control group [SMD = 3.50, 95%CI(1.45, 5.54)], and the heterogeneity test results showed I2 = 93.0%, p < 0.05. The mRNA expression levels of Muc5ac in lung tissue of mice in asthma group showed a higher level than that in control group [SMD = 4.46, 95%CI (3.38, 5.55)], and the heterogeneity test results showed I2 = 84.3%, p < 0.01. The protein expression levels of Muc5ac in lung tissue of mice in asthma group were significantly higher than those in control group [SMD = 5.70, 95%CI (4.09,7.31)], and the heterogeneity test results showed I2 = 89.7%, p < 0.01.The meta-analysis clarified the positive relationship between Muc5ac in lung and asthma. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported the protective effects of mesenchymal stem cell-derived exosomes (MSC-Exos) in reducing inflammation and decreasing conjunctival goblet cell (CGC) loss in dry eye disease. However, whether MSC-Exos provide anti-inflammatory profiles in macrophages, thus contributing to CGC protection, has remained elusive. Methods: Macrophages were incubated with PKH26‐labeled periodontal ligament mesenchymal stem cell-derived exosomes (PDLSC-Exos) for 12 h, and uptake of PDLSC-Exos by macrophages was observed by a confocal fluorescence microscope. The mRNA expression of TNF-α, IL-10, and Arg1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of TNF-α and IL-10 were quantified using western blotting. Then, CGCs were exposed to different macrophage supernatants and qRT-PCR was used to detect the Muc5ac mRNA expression of CGCs in response to or absence of cholinergic stimulation. ELISA was used to determine the Muc5ac secretion of CGCs in response to cholinergic stimulation. Results: The uptake of PDLSC-Exos by M1 macrophages facilitates M2 macrophage polarization with the elevated expressions of IL-10 and Arg1. In macrophage supernatant-treated CGCs systems, PDLSC-Exo-treated M1 macrophage supernatant significantly enhanced the Muc5ac expression of CGCs in response to, or in the absence of, cholinergic stimulation, while the addition of PDLSC-Exos to the control macrophage supernatant did not generate a change in Muc5ac expression. Conversely, the addition of PDLSC-Exos to the diluted control macrophage supernatant induced a significant increase in Muc5ac expression. Conclusion: PDLSC-Exos could protect CGCs against M1 macrophage-mediated inflammation, and the protective effects of PDLSC-Exos are partly attributable to their effects on M1 macrophages. [ABSTRACT FROM AUTHOR]

Background: To understand the connection between Muc5AC expression and the likelihood of rhinosinusitis, with the goal of providing insights into its prospective use as a biomarker. Methods: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies up to November 2023 to conduct a literature review. After screening and quality assessment, eligible studies meeting the criteria were included. Muc5AC expression and rhinosinusitis association was analyzed by STATA 14.0. Results: Including weighted mean difference and 95% confidence interval, were reported. The meta‐analysis included 16 studies with 1448 rhinosinusitis patients. MUC5AC expression was significantly up‐regulated in both chronic rhinosinusitis with nasal polyps (CRSwNP; WMD: 0.52; 95% CI: 0.41–0.63) and chronic rhinosinusitis without nasal polyps (CRSsNP; WMD: 0.42; 95% CI: 0.28–0.56) patients compared to controls. IHC positive area analysis corroborated these findings, with elevated MUC5AC levels in CRSwNP (WMD: 25.61; 95% CI: 22.41–28.81) and CRSsNP (WMD: 39.74; 95% CI: 25.6–53.88) patients. Subgroup analysis based on tissue type (nasal tissue fluid and sinus mucosa) consistently supported the overall results. Conclusion: Our meta‐analysis robustly demonstrates a significant association between elevated MUC5AC expression and rhinosinusitis risk. This finding underscores the potential of MUC5AC as a molecular marker, providing valuable insights for future research and potential therapeutic interventions in rhinosinusitis management. Systematic review registration: CRD42024518932. [ABSTRACT FROM AUTHOR]

Objective: To investigate regulatory effect and mechanism of protein kinase C (PKC)δ/θ-dual functional oxidase 1 (Duox1)-reactive oxygen species (ROS) signaling pathway on human airway mucin (MUC) 5AC, to provide a new target for treatment of high secretion of airway mucus. Methods: Human airway epithelial cells 16HBE were pretreated with PKC and its subunit PKCδ/θ inhibitor, Duox1 inhibitor or free radical scavenger DMTU, respectively, and then human neutrophil elastase (HNE) stimulation to establish an in vitro airway inflammatory cell model. Generation level of ROS in each group of cells was determined by kit, mRNA levels of Duox1 and MUC5AC were detected by real-time fluorescent quantitative PCR, influence of interfering factors of each group of cells on Duox1 protein level was determined by Western blot, and protein expression of MUC5AC in each group of cells was detected by ELISA and immunofluorescence. Results: Compared with control group, ROS production in HNE group was increased significantly, expressions of Duox1 and MUC5AC mRNA and protein were also increased (P<0.05). After administration of Duox1 inhibitors, free radical scavengers or PKC inhibitors and PKCδ/θ inhibitors, ROS production was significantly inhibited, Duox1 and MUC5AC mRNA and protein expressions were decreased (P<0.05), while after giving PKCα/β, ROS generation, Duox1 and MUC5AC mRNA and protein expressions were not significantly changed compared with HNE group (P>0.05). Conclusion: HNE can mediate high expression of MUC5AC through PKCδ/θ-Duox1-ROS, which plays an important role in development of high secretion of airway mucus in vitro cell model experiment. [ABSTRACT FROM AUTHOR]

ObjectiveGenome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) in chr11p15.5 region associated with asthma and idiopathic interstitial pneumonias (IIPs). We sought to identify functional genes for asthma by combining SNPs and mRNA expression in bronchial epithelial cells (BEC) in the Severe Asthma Research Program (SARP).MethodsCorrelation analyses of mRNA expression of six candidate genes (AP2A2, MUC6, MUC2, MUC5AC, MUC5B, and TOLLIP) and asthma phenotypes were performed in the longitudinal cohort (n = 156) with RNAseq in BEC, and replicated in the cross-sectional cohort (n = 155). eQTL (n = 114) and genetic association analysis of asthma severity (426 severe vs. 531 non-severe asthma) were performed, and compared with previously published GWASs of IIPs and asthma.ResultsHigher expression of AP2A2 and MUC5AC and lower expression of MUC5B in BEC were correlated with asthma, asthma exacerbations, and T2 biomarkers (P  0.8).ConclusionsSNPs associated with asthma in chr11p15.5 region are not associated with asthma severity neither with IIPs. Higher expression of MUC5AC and lower expression of MUC5B are risk for asthma but protective for IIPs.

BackgroundMucin family members have been reported to be widely expressed in gastric carcinoma with diverse functions. Several important mucins exert the function of tumorigenesis or progression in gastric cancer (GC). Here, we conduct this meta-analysis to evaluate the association between mucin expression and clinicopathological features in GC.MethodsLiterature searches were performed in PubMed, Embase, The Cochrane Library, and ISI Web of Science, and, finally, 28 studies met our criteria. Odds ratios or hazard ratios with 95% confidence intervals were calculated to evaluate the effect quantity. We analyzed the expression of MUC1, MUC2, MUC5AC, and MUC6 and their clinicopathological characteristics separately at the same time.ResultsTwenty-eight studies that contain 4,603 patients were included in our meta-analysis. MUC1 was associated with gender, Lauren classification, depth of tumor invasion, TNM, vascular invasion, lymph metastasis, and lymphatic invasion, WHO grade, as well as the 5-year survival rate. MUC2 was significantly correlated with lymphatic invasion and WHO grade. MUC5AC was highly positive in gender, depth of tumor invasion, WHO grade, TNM, lymph metastasis, and lymphatic invasion. Moreover, cases with decreased MUC5AC expression were correlated with less 5-year survival. MUC6 was only related with lymphatic invasion.ConclusionOur meta-analysis showed that MUC1 and MUC5AC had prognostic value in GC detected by immunohistochemistry. MUC1 and MUC5AC were also associated with some other significant clinicopathological parameters. Moreover, MUC2 and MUC6 also exert their influence in lymphatic invasion. However, further enlarged study awaits to verify our conclusion to deeply explore the role of mucin family members in GC.

To establish and characterize a dry eye model in New Zealand rabbits by subcutaneous injections of scopolamine hydrobromide (SCOP). Twenty New Zealand male rabbits were injected subcutaneously SCOP for 14 consecutive days; subcutaneous saline was used as a negative control. The correlated clinical parameters of ocular surface dryness were detected in vivo using tear secretion and corneal fluorescein staining. The expression of IL-1β and TNF-α on the ocular surface and in lacrimal glands were analyzed by real-time PCR and western blot on the 14th day. The expression of Mucin-5 subtype AC (MUC5AC) was detected by Immunofluorescence staining in conjunctival tissue. The SCOP-treated rabbits exhibited significantly decreased aqueous tear secretion and increased corneal fluorescein staining scores over time. Both the mRNA expression levels and the protein expression levels of IL-1β and TNF-α were significantly increased after SCOP treatment compared with those after saline treatment. The loss of conjunctival MUC5AC was found in the SCOP-injected rabbits. Some infiltrated inflammatory cells and atrophic acinar cells were observed in the lacrimal gland after SCOP treatment. The disordered structures of the ocular surface and lacrimal glands were also observed. This study showed that repeated subcutaneous SCOP injections successfully elicited some of the typical dry eye symptoms commonly seen in humans. [ABSTRACT FROM AUTHOR]

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059–0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes. [ABSTRACT FROM AUTHOR]

Objective To explore the therapeutic effects and mechanism of Yifei Jianpi Prescription on airway mucus hypersecretion in chronic obstructive pulmonary disease (COPD) rats through the epidermal growth factor receptor/ mitogen-activated protein kinase/mucin 5AC (EGFR/MAPK/MUC5AC) pathway. Methods Male SD rats were randomly divided into blank group, model group, ambroxol group and Yifei Jianpi Prescription low-, medium- and high-dose groups. The COPD rat model with lung and spleen deficiency was replicated by smoking combined with lipopolysaccharide instillation and administration of Folium Sennae. Alcian blue-periodic acid-Schiff staining (AB-PAS) was used to observe bronchial mucus secretion and the degree of goblet cell hyperplasia in rats. Hematoxylin-eosin staining (HE) was used to observe the pathological morphology of lung tissue of rats. Western Blot was used to detect the expression of MUC5AC, EGFR protein, c-Jun N-terminal kinase (JNK), p38 MAPK, protein and phosphorylated protein of extracellular regulated protein kinase (ERK) in rat lung tissues. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the mRNA expression of EGFR, JNK, p38 MAPK, MUC5AC, and ERK in rat lung tissues. Results AB-PAS staining showed that the number of goblet cells decreased significantly in ambroxol group and all dose groups of Yifei Jianpi Prescription. HE staining showed that ambroxol group and Yifei Jianpi high-dose group significantly improved the pathological injury of lung tissue. Compared with the blank group, the mRNA expressions of ERK, MUC5AC, p38 MAPK, JNK and EGFR were significantly increased in the lung tissues of the model group (P＜0.01), and the expression of MUC5AC and EGFR protein, as well as p38 MAPK, JNK, ERK total and phosphorylated protein were significantly increased (P＜0.01). Compared with model group, the protein expression levels of ambroxol group and Yifei Jianpi Prescription medium- and highdose groups were significantly decreased (P＜0.01, P＜0.05), while the protein expression levels of EGFR, p38 MAPK and p-p38 MAPK in Yifei Jianpi Prescription low-dose group were decreased (P＜0.01, P＜0.05). The mRNA expression of EGFR, ERK, JNK, p38 MAPK and MUC5AC in Yifei Jianpi Prescription high-dose and ambroxol groups were decreased (P＜0.01, P＜0.05), and the mRNA expression of MUC5AC in medium- and low-dose groups were decreased (P＜0.05). Conclusion Yifei Jianpi Prescription can reduce the expression of MUC5AC and improve hypersecretion of airway mucus. Its mechanism is related to the EGFR/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

CIC-rearranged sarcoma is an aggressive round cell sarcoma, and an alternative ATXN1/ATXN1L fusion has been reported. Diagnosis may be difficult, and molecular assays may suffer from imperfect sensitivity. Characteristic histology and ETV4 immunohistochemical positivity are diagnostically helpful. However, ETV4 staining is unavailable in most laboratories. Here, we explored the diagnostic utility of MUC5AC immunohistochemistry in CIC-rearranged sarcomas. All 30 cases, except one, of CIC-rearranged sarcomas and 2 ATXN1-rearranged sarcomas were positive for MUC5AC, although the number of immunopositive cells was generally low (< 5%) in most samples, representing a characteristic scattered pattern. The only MUC5AC-negative case had the lowest tumor volume. Among the 110 mimicking round cell malignancies, 12 tumors showed MUC5AC positivity, including occasional cases of synovial sarcoma and small cell carcinoma, whereas the remaining 98 samples were negative. Despite its lower specificity than that of ETV4 and sparse reactivity that requires careful interpretation, MUC5AC may serve as a useful marker for CIC/ATXN1-rearranged sarcoma because of its wider accessibility. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer ranks seventh in the world for cancer-related deaths in both sexes and causes. An accurate and timely diagnosis is necessary to maximize the treatment efficacy of pancreatic tumors. This benefit has been established by endoscopic ultrasonography-fine needle aspiration cytology. Immunohistochemical staining is a useful method for diagnosis that can speed up diagnosis and improve the precision of distinguishing between pancreatic lesions. Patients and methods: Our research's objective is to determine the benefits of adding MUC5AC, P53 immunohistochemical analysis for sensitivity and specificity of the endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) diagnosis of pancreatic ductal adenocarcinoma (PDAC). Results: The results of 141 EUS-FNAC specimens of pancreatic lesions using the Papanicolaou reporting system were as follows: 12 cases were classified as (I) nondiagnostic, 63 cases as (II) negative for malignancy, eight cases as (III) atypical, six cases as (IV) neoplastic: benign, 16 cases as (V) suspicious for malignancy, and 36 as (VI) malignant. Fifty-eight cases were identified as (III), (V), and (VI) and were subjected to further immunohistochemical staining of their cell blocks. Compared to the 68, 90, 97, and 37% of the EUS-FNAC analysis alone for the detection of PDAC, the sensitivity, specificity, positive predictive value, and negative predictive value of the combination of EUS-FNAC analysis with both P53 and MUC5AC were 86, 100, 100, and 59%. Conclusions: The sensitivity and specificity of the EUS-FNAC analysis combined with both P53 and MUC5AC were significantly greater than those of the cytological analysis alone, especially in indeterminate cases; it could help enhance PDAC's tissue diagnostic capabilities using EUS-FNAC. [ABSTRACT FROM AUTHOR]

Introduction. Determining the cause of postnasal drip syndrome can be quite challenging. Nasal septum deformation has been recognized as one possible factor. Understanding the fundamental processes of postnasal drip syndrome is crucial for developing targeted therapeutic strategies for treating this pathology. In our study, we examined the clinical and histological features of postnasal drip syndrome in individuals with nasal septum deformation and investigated the expression of mucopolysaccharides, specifically the indicators of MUC 5AC and MUC 1. The aim. This study aims to investigate the clinical and histological aspects of postnasal drip syndrome (PNDS) in patients with nasal septum deformation. Specifically, the study aims to explore the expression levels of MUC5AC and MUC1 in biopsies of the nasal turbinate mucosa. Materials and methods. A total of 29 samples of nasal mucosa from the lower nasal turbinates were collected. These samples were divided into two groups: patients with nasal septum deviation with and without postnasal drip syndrome. Levels of MUC5AC and MUC1 were determined using Western blot analysis. Results. Upon analysis of histological sections, we identified a significant increase in tissue metaplasia and lymphoid infiltration in the nasal mucosa of patients with postnasal drip syndrome compared to the control group. The levels of mucopolysaccharides, MUC5AC and MUC1, were higher in the nasal mucosa of the research group compared to the control group. Conclusions. The obtained data suggest that anatomical changes in the nasal cavity may play a role in the development of postnasal drip syndrome through alterations in mucin secretion.

Simple Summary: It is generally reported that the prognostic factors for ampulla of Vater cancer include T stage, N stage, and lymphovascular invasion and subtype, and the meaning of MUC stain is controversial. This retrospective study by the authors evaluated the significance of various MUC stains in AoV cancer using single-center clinicopathological data. The results showed that MUC5AC was significant for lymph node metastasis and was furthermore valuable as a prognostic factor for predicting overall survival. If this is evaluated in addition to the hematoxylin and eosin stain, which is commonly performed in preoperative biopsy, it is expected to be a method to select groups that require more extensive LN dissection and further prevent locoregional recurrence. Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results: Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions: Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer. [ABSTRACT FROM AUTHOR]

Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high‐risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, a prospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase‐polymerase chain reaction. Life‐threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty‐two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild disease compared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity. [ABSTRACT FROM AUTHOR]

Airway mucus hypersecretion is an important pathophysiological and clinical manifestation of a variety of chronic airway diseases, and is an independent risk factor affecting the prognosis and outcome of the disease. Azithromycin can effectively prevent or reduce the acute exacerbation of chronic airway diseases and inhibit the hypersecretion of airway mucus in chronic airway diseases. However, the specific mechanism is not completely clear, which may be related to the inhibition of the synthesis and secretion of mucin MUC5AC and the inhibition of bacterial biofilm formation. This article summarizes the possible mechanism of azithromycin in inhibiting airway mucus hypersecretion and its application in chronic airway diseases, in order to provide reference for the follow-up study and clinical application of azithromycin. [ABSTRACT FROM AUTHOR]

BackgroundOverexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model.Materials and methodsMUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously.ResultsIn the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465).ConclusionMUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

Abstract Background Lianhua Qingke (LHQK) is an effective traditional Chinese medicine used for treating acute tracheobronchitis. In this study, we evaluated the effectiveness of LHQK in managing airway mucus hypersecretion in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods The AECOPD model was established by subjecting male Wistar rats to 12 weeks of cigarette smoke (CS) exposure (80 cigarettes/day, 5 days/week for 12 weeks) and intratracheal lipopolysaccharide (LPS) exposure (200 μg, on days 1, 14, and 84). The rats were divided into six groups: control (room air exposure), model (CS + LPS exposure), LHQK (LHQK-L, LHQK-M, and LHQK-H), and a positive control group (Ambroxol). H&E staining, and AB-PAS staining were used to evaluate lung tissue pathology, inflammatory responses, and goblet cell hyperplasia. RT-qPCR, immunohistochemistry, immunofluorescence and ELISA were utilized to analyze the transcription, expression and secretion of proteins related to mucus production in vivo and in the human airway epithelial cell line NCI-H292 in vitro. To predict and screen the active ingredients of LHQK, network pharmacology analysis and NF-κB reporter system analysis were employed. Results LHQK treatment could ameliorate AECOPD-triggered pulmonary structure damage, inflammatory cell infiltration, and pro-inflammatory cytokine production. AB-PAS and immunofluorescence staining with CCSP and Muc5ac antibodies showed that LHQK reduced goblet cell hyperplasia, probably by inhibiting the transdifferentiation of Club cells into goblet cells. RT-qPCR and immunohistochemistry of Muc5ac and APQ5 showed that LHQK modulated mucus homeostasis by suppressing Muc5ac transcription and hypersecretion in vivo and in vitro, and maintaining the balance between Muc5ac and AQP5 expression. Network pharmacology analysis and NF-κB luciferase reporter system analysis provided insights into the active ingredients of LHQK that may help control airway mucus hypersecretion and regulate inflammation. Conclusion LHQK demonstrated therapeutic effects in AECOPD by reducing inflammation, suppressing goblet cell hyperplasia, preventing Club cell transdifferentiation, reducing Muc5ac hypersecretion, and modulating airway mucus homeostasis. These findings support the clinical use of LHQK as a potential treatment for AECOPD.

Abstract Background Bei Mu Gua Lou San (BMGLS) is an ancient formulation known for its moisturizing and expectorant properties, but the underlying mechanisms remain unknown. We investigated concentration-dependent effects of BMGLS on its rehydrating and mucus-modulating properties using an air-liquid-interface (ALI) cell culture model of the Calu-3 human bronchial epithelial cell line and primary normal human bronchial epithelial cells (NHBE), and specifically focused on quantity and composition of the two major mucosal proteins MUC5AC and MUC5B. Methods ALI cultures were treated with BMGLS at different concentrations over three weeks and evaluated by means of histology, immunostaining and electron microscopy. MUC5AC and MUC5B mRNA levels were assessed and quantified on protein level using an automated image-based approach. Additionally, expression levels of the major mucus-stimulating enzyme 15-lipoxygenase (ALOX15) were evaluated. Results BMGLS induced concentration-dependent morphological changes in NHBE but not Calu-3 ALI cultures that resulted in increased surface area via the formation of herein termed intra-epithelial structures (IES). While cellular rates of proliferation, apoptosis or degeneration remained unaffected, BMGLS caused swelling of mucosal granules, increased the area of secreted mucus, decreased muco-glycoprotein density, and dispensed MUC5AC. Additionally, BMGLS reduced expression levels of MUC5AC, MUC5B and the mucus-stimulating enzyme 15-lipoxygenase (ALOX15). Conclusions Our studies suggest that BMGLS rehydrates airway mucus while stimulating mucus secretion by increasing surface areas and regulating goblet cell differentiation through modulating major mucus-stimulating pathways.

Background: Initially, contact lenses were recommended only for daily wear because of infection and discomfort concerns. With rising demand, particularly for overnight use, extended wear lenses have gained significance. Despite concerns, intensive development of materials like Lotrafilcon B aims to meet this demand, focusing on comfort and safety. Aim: This study aimed to evaluate the mucin quantity and quality changes between daily and extended wear (Lotrafilcon B), impacting eye health and comfort. Setting: The study was conducted at Kirana Eye Center, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Methods: This study was a single-blinded randomised clinical trial with two parallel groups. Forty (40) eligible subjects willingly participated. Mucin 5AC (MUC5AC) and Ferning-type tests were conducted. The 40 subjects with moderate myopia were then divided into a daily wear and an extended wear group. The MUC5AC test was performed at pre-fitting and at 4 weeks, whereas the Ferning-type tests were taken at pre-fitting and 1st and 4th weeks. Results: For both groups, there was a significant increase in MUC5AC levels from pre-fitting to week four, but with no significant difference between them in final MUC5AC levels. Additionally, the comparison of eyes with normal and abnormal Ferning-types between the two groups showed no significant differences at pre-fitting, 1st and 4th weeks. Conclusion: There is no significant difference in MUC5AC levels with the use of daily or extended wear (with Lotrafilcon B). Contribution: This study compares the impact of daily and extended wear Lotrafilcon B contact lenses on eye health and comfort in moderate myopia patients.

Introduction: Allergic airway diseases are one of the serious health problems in worldwide and allergic airway inflammation is a prerequisite led to the exacerbated situation such as mucus hypersecretion, epithelial barrier damage and microbiota dysbiosis. Because of side effects and low efficiencies of current therapeutics, the need for novel alternatives has been urged. Probiotics in which have diverse and beneficial modulatory effects have been applied to the airway inflammation model and the underlying mechanism needs to be investigated. Methods: We aimed to evaluate whether our target strain, Lactiplantibacillus plantarum APsulloc331261 (GTB1TM) isolated from green tea, can ameliorate allergic airway inflammation in mice and to figure out the mechanism. We induced allergic airway inflammation to mice by ovalbumin (OVA) and administered GTB1 orally and the immune and epithelial barrier markers were assessed. The gut metabolite and microbiota were also analysed, and the in vitro cell-line experiment was introduced to confirm the hypothesis of the study. Results: GTB1 ameliorated type 2 inflammation and suppressed mucin hypersecretion with the inhibition of MUC5AC in inflamed mice. Moreover, GTB1 increased the butyrate production and the relative abundance of butyrate producer, Clostridium cluster IV. We assumed that butyrate may have a potential role and investigated the effect of butyrate in mucin regulation via human airway epithelial cell line, A549. Butyrate significantly reduced the gene expression of MUC5AC in A549 cells suggesting its regulatory role in mucus production. Conclusion: Therefore, our study demonstrates that the oral administration of GTB1 can ameliorate allergic airway inflammation and mucin hypersecretion by butyrate production. [ABSTRACT FROM AUTHOR]

To investigate the antiproliferative properties of exopolysaccharides (EPS) on human colorectal adenocarcinoma cell line (Caco-2) and the regulation of MUC5AC gene expression, the antiproliferative effect of EPS isolated from D36 strain was determined by MTT test and the regulation of MUC5AC gene expression was examined using Real-Time PCR. Enterococcus faecium D36 (E. faecium D36) were characterized by Ribotyping analysis. Some biochemical methodologies were preliminarily used to characterize the probiotic potential of E. faecium D36, including morphological, cultural, and physiological characteristics. EPS isolated from E. faecium D36 strain has an antiproliferative effect on Caco-2 cell line, and mucin gene (MUC5AC) expression levels decreased. These results suggest that EPS isolated from E. faecium D36 strain might be a source for a novel anticancer agent. Based on our results, it is believed that EPS obtained from E. faecium D36 can be used as a protective and therapeutic substance during the early stages of cancer, especially colon cancer. EPS affects colon cancer by reducing the invasion ability of cancer by decreasing MUC5AC expression. These findings are thought to shed light on future in vivo studies. [ABSTRACT FROM AUTHOR]

Abstract YPL-001 is a drug substance of Pseudolysimachion rotundum var. subintegrum and has been reported to be a potent COPD inhibitor. For the first time, this study demonstrated a correlation among the iridoid constituents, antioxidants, and MUC5AC inhibition activities in P. rotundum during different growth stages (5 to 11 weeks). Single-factor extraction was used to optimize the plant extraction conditions to maximize the major iridoid constituents (70% ethanol, 40 °C, 1 h); isolated metabolites 1–6 were identified using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The contents of each metabolite and antioxidant/MUC5AC inhibition effects were markedly changed according to the growth stages, especially for catalposide (2, 5.97 → 10.99 mg/g, 1.8-fold) and isovanillyl catapol (5, 4.42 → 20.00 mg/g, 4.5-fold), which were the predominant substances in August. Our results indicated that YPL-001 could potentially contribute to enhancing the P. rotundum value in accumulated iridoids at the growth stage and the biological effect aspects to develop industrial medicinal crops.

IntroductionAllergic airway diseases are one of the serious health problems in worldwide and allergic airway inflammation is a prerequisite led to the exacerbated situation such as mucus hypersecretion, epithelial barrier damage and microbiota dysbiosis. Because of side effects and low efficiencies of current therapeutics, the need for novel alternatives has been urged. Probiotics in which have diverse and beneficial modulatory effects have been applied to the airway inflammation model and the underlying mechanism needs to be investigated.MethodsWe aimed to evaluate whether our target strain, Lactiplantibacillus plantarum APsulloc331261 (GTB1TM) isolated from green tea, can ameliorate allergic airway inflammation in mice and to figure out the mechanism. We induced allergic airway inflammation to mice by ovalbumin (OVA) and administered GTB1 orally and the immune and epithelial barrier markers were assessed. The gut metabolite and microbiota were also analysed, and the in vitro cell-line experiment was introduced to confirm the hypothesis of the study.ResultsGTB1 ameliorated type 2 inflammation and suppressed mucin hypersecretion with the inhibition of MUC5AC in inflamed mice. Moreover, GTB1 increased the butyrate production and the relative abundance of butyrate producer, Clostridium cluster IV. We assumed that butyrate may have a potential role and investigated the effect of butyrate in mucin regulation via human airway epithelial cell line, A549. Butyrate significantly reduced the gene expression of MUC5AC in A549 cells suggesting its regulatory role in mucus production.ConclusionTherefore, our study demonstrates that the oral administration of GTB1 can ameliorate allergic airway inflammation and mucin hypersecretion by butyrate production.

Allergic rhinitis (AR) is a disease that is difficult to cure and accompanies the patient's life. Proinflammatory cytokines (GM‑CSF and eotaxin) and MUC5AC are key mediators promoting AR progression. Herein, the function of lncRNA ZFAS1 in AR was investigated. Nasal epithelial cells (NECs) were subjected to 50 ng/mL IL‐13 for 24 h to construct an AR cell model. The mRNA and protein expressions were assessed using qRT‐PCR and western blot. The levels of GM‑CSF, eotaxin, IL‐1β, IL‐6, TNF‐α and MUC5AC in cell supernatant were examined by ELISA. The binding relationships between HDAC3, ZFAS1, miR‐7‐5p and SIRT1 were analysed using dual luciferase reporter or ChIP assays. Herein, our results displayed that ZFAS1 and SIRT1 were lowly expressed in AR, while miR‐7‐5p and HDAC3 were highly expressed. Functional experiments displayed that ZFAS1 overexpression suppressed IL‐13‐induced proinflammatory cytokines and mucin production in NECs. The highly expressed HDAC3 in AR inhibited ZFAS1 expression by binding with ZFAS1 promoter. In addition, our experiments revealed that ZFAS1 targeted miR‐7‐5p, and miR‐7‐5p targeted SIRT1. As expected, miR‐7‐5p overexpression or SIRT1 silencing abrogated ZFAS1 upregulation's repression on IL‐13‐induced proinflammatory cytokines and MUC5AC secretory levels in NECs. ZFAS1 suppressed proinflammatory cytokines, inflammatory cytokines, and MUC5AC secretory levels in AR by regulating the miR‐7‐5p/SIRT1 axis. Thus, our work suggested that ZFAS1 might serve as a novel target for AR treatment and prevention. [ABSTRACT FROM AUTHOR]

Gallbladder mucocele (GBM) is one of the most common gallbladder diseases in dogs. Its pathogenesis has not yet been clarified, but excessive accumulation of a secretory gel–forming mucin, MUC5AC in the gallbladder has been reported. This study aimed to ascertain if MUC5AC overproduction resulted in mucus accumulation in the gallbladder during GBM development. Eleven dogs undergoing cholecystectomy who were pathologically diagnosed with GBM were included, and the expression level of mucins, particularly MUC5AC and MUC5B, in their gallbladder epithelial cells was compared with those in normal gallbladder epithelial cells. On reverse transcriptionquantitative polymerase chain reaction screening, there was a significant difference (P<0.05) in the mRNA expression level of MUC1, but not of other mucins including MUC5AC and MUC5B, between mucocele and normal gallbladder epithelial cells. Protein expression levels were also evaluated for MUC5AC and MUC5B using immunohistochemistry. There was little immunoreactivity for MUC5AC, whereas MUC5B showed definitive staining in gallbladder epithelial cells. There was no difference in MUC5AC and MUC5B protein expression levels between mucocele and normal gallbladder epithelial cells. These data suggest that excessive production of mucin, especially MUC5AC and MUC5B, does not occur in canine GBM, and that abnormal mucus excretion, rather than excessive mucus production, may be the cause of GBM development. [ABSTRACT FROM AUTHOR]

Background: Lianhua Qingke (LHQK) is an effective traditional Chinese medicine used for treating acute tracheobronchitis. In this study, we evaluated the effectiveness of LHQK in managing airway mucus hypersecretion in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The AECOPD model was established by subjecting male Wistar rats to 12 weeks of cigarette smoke (CS) exposure (80 cigarettes/day, 5 days/week for 12 weeks) and intratracheal lipopolysaccharide (LPS) exposure (200 μg, on days 1, 14, and 84). The rats were divided into six groups: control (room air exposure), model (CS + LPS exposure), LHQK (LHQK-L, LHQK-M, and LHQK-H), and a positive control group (Ambroxol). H&E staining, and AB-PAS staining were used to evaluate lung tissue pathology, inflammatory responses, and goblet cell hyperplasia. RT-qPCR, immunohistochemistry, immunofluorescence and ELISA were utilized to analyze the transcription, expression and secretion of proteins related to mucus production in vivo and in the human airway epithelial cell line NCI-H292 in vitro. To predict and screen the active ingredients of LHQK, network pharmacology analysis and NF-κB reporter system analysis were employed. Results: LHQK treatment could ameliorate AECOPD-triggered pulmonary structure damage, inflammatory cell infiltration, and pro-inflammatory cytokine production. AB-PAS and immunofluorescence staining with CCSP and Muc5ac antibodies showed that LHQK reduced goblet cell hyperplasia, probably by inhibiting the transdifferentiation of Club cells into goblet cells. RT-qPCR and immunohistochemistry of Muc5ac and APQ5 showed that LHQK modulated mucus homeostasis by suppressing Muc5ac transcription and hypersecretion in vivo and in vitro, and maintaining the balance between Muc5ac and AQP5 expression. Network pharmacology analysis and NF-κB luciferase reporter system analysis provided insights into the active ingredients of LHQK that may help control airway mucus hypersecretion and regulate inflammation. Conclusion: LHQK demonstrated therapeutic effects in AECOPD by reducing inflammation, suppressing goblet cell hyperplasia, preventing Club cell transdifferentiation, reducing Muc5ac hypersecretion, and modulating airway mucus homeostasis. These findings support the clinical use of LHQK as a potential treatment for AECOPD. [ABSTRACT FROM AUTHOR]

This study explores the potential of a natural composite formulation known as ED, consisting of Ecklonia cava (E. cava, family: Lessoniaceae) and Chrysanthemum indicum Linne (C. indicum, family: Asteraceae), in alleviating lung inflammation induced by fine particulate matter (PM2.5). Initial assessments confirmed that neither ED nor one of its components, dieckol, exhibited cytotoxic effects on A549 cells. Subsequently, the impact of ED and dieckol on MUC5AC gene expression in A549 cells stimulated by phorbol 12-myristate 13-acetate (PMA) was investigated, revealing promising results that demonstrated a dose-dependent inhibition of MUC5AC gene expression. The study also delves into the underlying mechanisms, demonstrating that ED and dieckol effectively suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38, which are known to be involved in the regulation of MUC5AC gene expression. In in vivo experiments using a PM2.5-induced pulmonary inflammation mouse model, the research findings showed that ED mitigated cellular accumulation in the airways, leading to a significant reduction in the total cell count in bronchoalveolar lavage fluid (BALF). Moreover, ED exhibited protective effects against PM2.5-induced pulmonary damage, characterized by reduced inflammatory cell infiltration and decreased mucus secretion in pulmonary tissues. Additionally, ED's anti-inflammatory properties were evident in its ability to decrease the levels of key inflammatory cytokines, TNF-α and IL-6, both in the serum and lung tissue of the PM2.5-induced pulmonary inflammation mouse model. These findings suggest the potential of ED as a therapeutic agent for inflammatory respiratory diseases. [ABSTRACT FROM AUTHOR]

Objective.To investigate the expression of mucin 5AC (MUC5AC) in airway of children with mycoplasma pneumoniae pneumonia(MPP), and to provide clinical value for early diagnosis and treatment of MPP mucus plug. Methods.A total of 94 children with MPP who were hospitalized for alveolar lavage from April 2022 to October 2022 were included in the MPP group. According to whether mucus plug was observed under the first fiberoptic bronchoscope, the MPP group was divided into mucus plug group (n = 41) and non-mucus plug group (n = 53). Relevant clinical data and laboratory examination data were collected. Results.Compared with non mucus plug group, the mucus plug group had a longer heat duration and hospital stay, and the levels of CRP, LDH,PCT, D-dimer, MP-DNA copy value of lavage fluid, IL-17, MUC5AC were all increased,with statistically significant differences (P < 0.05). MUC5AC was positively correlated with LDH and IL-17 levels (r = 0.54, P = 0.002, r = 0.39, P = 0.019). The ROC curve plotted based on the level of MUC5AC had an area under the ROC curve of 0.811, a sensitivity of 86.2% and a specificity of 71.4% for predicting formation of mucus plug in MPP. Conclusions.There was an increase in the level of MUC5AC in children with mucus plug group in MPP, and the level of MUC5AC had a certain value for predicting mucus plug formation. [ABSTRACT FROM AUTHOR]

Simple Summary: MUC5AC is a mucin with unclear importance in pancreatic cancers. Recent studies suggest the existence of two major classes of this mucin, which differ in location and function. Prior studies did not clearly establish the role of both kinds of MUC5AC in pancreatic cancer. We attempted to study their differential expression in non-cancer and cancer tissues and also tried to establish their impact in cancer tissues. We explored the differential expression and diagnostic value of two significant Mucin 5AC (MUC5AC) glycoforms, less-glycosylated immature (IM) and heavily-glycosylated mature (MM), in neoplastic diseases (NpD), including pancreatic ductal adenocarcinoma (PDA) and neuroendocrine tumors (NET), and non-neoplastic (non-NpD) diseases. Commercially available tissue microarray (TMA) was constructed from 96 patients, including 38 primary PDA (PT), 5 metastatic lesions (ML), 11 NET, and the rest being non-NpD tissues. Immunohistochemistry for MUC5AC was performed using CHL2 and 45M1 clones for IM and MM isoforms, respectively. MUC5AC (both glycoforms) are not detected in non-NpD. In MUC5AC-positive neoplastic tissues, IM was localized to the cytoplasm (Cy) while MM was identified in apical (Ap) and extracellular (Ec) regions too. One ML positive (omentum) in the TMA expressed both. For PDA vs. non-PDA, the sensitivity (SN) was higher with MM ± IM (71%) than MM (47%) or IM (65%)-alone. The specificity (SP) was 100% with MM-alone, which dropped with the addition of IM (96%) or IM-alone (93%). For NpD vs. non-NpD, the SN (MM + IM-59%, IM-55%, MM-37%) was inferior, and SP was 100% for both glycoforms (MM ± IM). The combination of MUC5AC glycoforms has high SP and reasonable SN to diagnose PDA. They have the potential to be a reliable diagnostic marker and should be investigated further in more extensive studies. [ABSTRACT FROM AUTHOR]

Abstract Introduction Myopia prevalence among adolescents is increasing annually. While orthokeratology (OK) is effective for controlling myopia progression, it may also be detrimental. We investigated tear film parameters [including tear mucin 5AC (MUC5AC) concentration] in children and adolescents with myopia treated with spectacles or OK compared with those with emmetropia. Methods This prospective case–control study enrolled children (aged 8–12 years; 29 and 39 with myopia treated with OK and spectacles, respectively, and 25 with emmetropia) and adolescents (aged 13–18 years; 38 and 30 with myopia treated with OK and spectacles, respectively, and 18 with emmetropia). We recorded the ocular surface disease index (OSDI), visual analog scale (VAS) score, tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), meibomian gland score (meiboscore), ocular redness score, and tear MUC5AC concentration in the emmetropia, spectacle (after 12 months of spectacle wearing), and OK (baseline, and after 1-, 3-, 6-, and 12-month use) groups. We observed changes from baseline to 12 months in the OK group and compared parameters among the spectacle, 12-month OK, and emmetropia groups. Results The 12-month OK group differed significantly from the spectacle and emmetropia groups in most indicators among children and adolescents (P

Abstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI‐H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real‐time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP‐AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2‐induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild‐type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.

Abstract Background The respiratory tract is protected from inhaled particles and microbes by mucociliary clearance, mediated by the mucus and the cilia creating a flow to move the mucus cephalad. Submucosal glands secrete linear MUC5B mucin polymers and because they pass through the gland duct before reaching the airway surface, bundled strands of 1000–5000 parallel molecules exit the glands. In contrast, the surface goblet cells secrete both MUC5AC and MUC5B. Methods We used mass-spectrometry based proteomic analysis of unstimulated and carbachol stimulated newborn wild-type (WT) and cystic fibrosis transmembrane conductance regulator (CFTR) null (CF) piglet airways to study proteins in the airway surface liquid and mucus, to investigate if levels of MUC5AC and MUC5B were affected by carbachol stimulation and whether the proteins clustered according to function. Results Proteins in the first four extracted fractions clustered together and the fifth fraction contained the mucus cluster, mucins and other proteins known to associate with mucins, whereas the traditional airway surface liquid proteins clustered to fraction 1–4 and were absent from the mucus fraction. Carbachol stimulation resulted in increased MUC5AC and MUC5B. Conclusions These results indicate a distinct separation between proteins in the washable surface liquid and the mucus fraction. In fractions 1–4 from newborn CF piglets an additional cluster containing acute phase proteins was observed, suggesting an early inflammatory response in CF piglets. Alternatively, increased levels of these proteins could indicate altered lung development in the CF piglets. This observation suggests that CF airway disease is present at birth and thus, treatment should commence directly after diagnosis.

Abstract Chronic obstructive pulmonary disease (COPD) is an irreversible disease with the leading causes of morbidity, mortality, and several physical limitations. Isodon Suzhouensis is a unique Chinese medicinal plant used for both medicine and food. It possesses strong anti‐inflammatory effects that may treat COPD. Considering the fact that the effects of Isodon Suzhouensis extract (WZZE) and its active ingredient glaucocalyxin A (GLA) on COPD have never been reported before, this study aimed to investigate the effects of WZZE and GLA against COPD and its underlying mechanistic pathway in COPD model rats or in CSE‐induced NR8383 cells. The variation in lung physiology was measured through spirometry while histopathological changes were studied via H&E staining of the COPD model rats lung samples. The levels of cytokine and other immunomodulatory proteins were determined by ELISA. Apoptosis of lung tissue cells was detected by TUNEL staining. Western blot and immunohistochemistry were used to detect the expression of related pathways and other proteins. The results show that WZZE improved the relevant lung function indicators, while restoring the activity of immunoglobulins (Ig A, IgG) and inhibiting the levels of TNF‐α and IL‐1β in serum and bronchoalveolar lavage fluid, thereby improving the body's immunity and inhibiting inflammation of the airways and lungs, slowing the progression of COPD. The results of H&E staining indicated that WZZE is capable of improving the pathological injury associated with COPD. In addition, the administration of WZZE reduced the expression of MUC5AC protein induced and the apoptosis rate of lung tissue cells in COPD model rats. The results also showed that WZZE significantly increased the expression of SOCS3 and inhibited the expression of JAKs/STATs pathway‐related proteins in COPD rats. In addition, GLA can also upregulate the expression of SOCS3 protein, inhibit JAKs/STATs pathway, inhibit the expression level of MUC5AC, upregulate the expression level of immunoglobulin, and downregulate the expression level of proinflammatory factors in NR8383 cells induced by CSE. Present study findings suggest that WZZE and GLA may ameliorate the progression of COPD via the SOCS3–JAKs/STATs pathway in COPD rats or in CSE‐induced NR8383.

Objectives. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs). Methods. In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining. Results. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs. Conclusion. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

Introduction: Eotaxin-2 and -3 of the C-C chemokine subfamily function as potent chemoattractant factors for eosinophil recruitment and various immune responses in allergic and inflammatory airway diseases. Mucin 5AC (MUC5AC), a major gel-forming secretory mucin, is overexpressed in airway inflammation. However, the association between mucin secretion and eotaxin-2/3 expression in the upper and lower airway epithelial cells has not been fully elucidated. Therefore, in this study, we investigated the effects of eotaxin-2/3 on MUC5AC expression and its potential signaling mediators. Methods: We analyzed the effects of eotaxin-2 and -3 on NCI-H292 human airway epithelial cells and primary human nasal epithelial cells (HNEpCs) via reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Along with immunoblot analyses with specific inhibitors and small interfering RNA (siRNA), we explored the signaling pathway involved in MUC5AC expression following eotaxin-2/3 treatment. Results: In HCI-H292 cells, eotaxin-2/3 activated the mRNA expression and protein production of MUC5AC. A specific inhibitor of C-C motif chemokine receptor 3 (CCR3), SB328437, suppressed eotaxin-2/3-induced MUC5AC expression at both the mRNA and protein levels. Eotaxin-2/3 induced the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and p38, whereas pretreatment with a CCR3 inhibitor significantly attenuated this effect. Induction of MUC5AC expression with eotaxin-2/3 was decreased by U0126 and SB203580, specific inhibitors of ERK1/2 and p38 mitogen-activated protein kinase (MAPK), respectively. In addition, cell transfection with ERK1/2 and p38 siRNAs inhibited eotaxin-2/3-induced MUC5AC expression. Moreover, specific inhibitors (SB328437, U0126, and SB203580) attenuated eotaxin-2/3-induced MUC5AC expression in HNEpCs. Conclusion: Our results imply that CCR3-mediated ERK1/2 and p38 MAPK are involved in the signal transduction of eotaxin-2/3-induced MUC5AC overexpression. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with a number of complications, in particular, gastrointestinal tract dysfunction. Impaired mucin secretion by the gastric mucosa in rats with T2DM may affect the absorption of drugs in the stomach and may explain the poor efficacy of treatment and correction of the condition. The aim of our work was to study changes in mucin secretion by the mucous membrane of the gastric fundus in rats with T2DM and the administration of metformin in combination with propionate. T2DM was modelled in rats by a high-fat diet for 3 months with a single administration of streptozotocin (25 mg/kg). Pharmacological correction was performed by intragastric administration of metformin (60 mg/kg), propionate (60 mg/kg), and combined administration of the mentioned drugs for 14 days. Structural changes in the gastric mucosa and mucopolysaccharide secretion activity were assessed by histochemistry. Western blot analysis of MUC5AC expression was performed. A significant decrease in mucin production was observed in the lower stomach of rats, which was associated with a decrease in the density of cells actively producing acidic mucopolysaccharides. Metformin administration to animals with T2DM did not restore mucin production in the gastric fundus, whereas propionate administration increased acid mucopolysaccharide secretion. An increase in the neutral component of mucus and MUC5AC was found in T2DM. The combined administration of metformin and propionate helped to reduce the content of this mucin. The identified morphofunctional changes in the gastric fundus require further research and should be taken into account when using oral hypoglycaemic drugs because the loss of the mucin barrier layer may affect the state of the gastric mucosa and the absorption of drugs. [ABSTRACT FROM AUTHOR]

Background: Bei Mu Gua Lou San (BMGLS) is an ancient formulation known for its moisturizing and expectorant properties, but the underlying mechanisms remain unknown. We investigated concentration-dependent effects of BMGLS on its rehydrating and mucus-modulating properties using an air-liquid-interface (ALI) cell culture model of the Calu-3 human bronchial epithelial cell line and primary normal human bronchial epithelial cells (NHBE), and specifically focused on quantity and composition of the two major mucosal proteins MUC5AC and MUC5B. Methods: ALI cultures were treated with BMGLS at different concentrations over three weeks and evaluated by means of histology, immunostaining and electron microscopy. MUC5AC and MUC5B mRNA levels were assessed and quantified on protein level using an automated image-based approach. Additionally, expression levels of the major mucus-stimulating enzyme 15-lipoxygenase (ALOX15) were evaluated. Results: BMGLS induced concentration-dependent morphological changes in NHBE but not Calu-3 ALI cultures that resulted in increased surface area via the formation of herein termed intra-epithelial structures (IES). While cellular rates of proliferation, apoptosis or degeneration remained unaffected, BMGLS caused swelling of mucosal granules, increased the area of secreted mucus, decreased muco-glycoprotein density, and dispensed MUC5AC. Additionally, BMGLS reduced expression levels of MUC5AC, MUC5B and the mucus-stimulating enzyme 15-lipoxygenase (ALOX15). Conclusions: Our studies suggest that BMGLS rehydrates airway mucus while stimulating mucus secretion by increasing surface areas and regulating goblet cell differentiation through modulating major mucus-stimulating pathways. [ABSTRACT FROM AUTHOR]

PM2.5 can cause airway inflammation and promote the excessive secretion of mucin 5ac (Muc5ac), which can further induce many respiratory diseases. Antisense non‐coding RNA in the INK4 locus (ANRIL) might regulate the inflammatory responses mediated by nuclear factor kappa‐B (NF‐κB) signaling pathway. Beas‐2B cells were used to clarify the role of ANRIL in the secretion of Muc5ac induced by PM2.5. The siRNA was used to silence ANRIL expression. Normal and gene silenced Beas‐2B cells were respectively exposed to different doses of PM2.5 for 6, 12, and 24 h. The survival rate of Beas‐2B cells was detected by methyl thiazolyl tetrazolium (MTT) assay. Tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and Muc5ac levels were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of NF‐κB family genes and ANRIL were detected by real time polymerase chain reaction (PCR). The levels of NF‐κB family proteins and NF‐κB family phosphorylated proteins were determined using Western blot. Immunofluorescence experiments were performed to observe the nuclear transposition of RelA. PM2.5 exposure increased the levels of Muc5ac, IL‐1β and TNF‐α, and ANRIL gene expression (p <.05). With the dose and time of PM2.5 exposure increasing, the protein levels of inhibitory subunit of nuclear factor kappa‐B alpha (IκB‐α), RelA, and NF‐κB1 decreased, the protein levels of phosphorylated RelA (p‐RelA) and phosphorylated NF‐κB1 (p‐NF‐κB1) increased, and RelA nuclear translocation increased, which indicated that the NF‐κB signaling pathway was activated (p <.05). Silencing ANRIL could decrease the levels of Muc5ac, IL‐1β, TNF‐α, decrease NF‐κB family genes expression, inhibit the degradation of IκB‐α and the activation of NF‐κB pathway (p <.05). ANRIL played a regulatory role in the secretion of Muc5ac and the inflammation induced by atmospheric PM2.5 via NF‐κB pathway in Beas‐2B cells. ANRIL could be a target for prevention and treatment of the respiratory diseases caused by PM2.5. [ABSTRACT FROM AUTHOR]

Studies investigating the potential role of circulating bile acids (BAs) as diagnostic biomarkers for cholangiocarcinoma (CCA) are sparse and existing data do not adjust for confounding variables. Furthermore, the mechanism by which BAs affect the expression of the oncogenic mucin 5AC (MUC5AC) has never been investigated. We performed a case–control study to characterise the profile of circulating BAs in patients with CCA (n = 68) and benign biliary disease (BBD, n = 48) with a validated liquid chromatography–tandem mass spectrometry technique. Odd ratios (OR) for CCA associations were calculated with multivariable logistic regression models based on a directed acyclic graph structure learning algorithm. The most promising BAs were then tested in an in vitro study to investigate their interplay in modulating MUC5AC expression. The total concentration of BAs was markedly higher in patients with CCA compared with BBD controls and accompanied by a shift in BAs profile toward a higher proportion of primary conjugated BAs (OR = 1.50, CI: 1.14 to 1.96, p = 0.003), especially taurochenodeoxycholic acid (TCDCA, OR = 42.29, CI: 3.54 to 504.63, p = 0.003) after multiple adjustments. Western blot analysis of secreted MUC5AC in human primary cholangiocytes treated with primary conjugated BAs or with TCDCA alone allowed us to identify a novel 230 kDa isoform, possibly representing a post-translationally modified MUC5AC specie. [ABSTRACT FROM AUTHOR]

A component of the tear film, mucin is produced by conjunctival goblet cells and is crucial to preserving the tear film's stability. Severe thermal burns, chemical burns, and severe ocular surface diseases can cause extensive damage to the conjunctiva, destroy the secretory function of goblet cells, and affect the stability of the tear film and integrity of the ocular surface. Currently, the expansion efficiency of goblet cells in vitro is low. In this study, we observed that rabbit conjunctival epithelial cells exhibited dense colony morphology after stimulation with the Wnt/β-catenin signaling pathway activator CHIR-99021 and promoted the differentiation of conjunctival goblet cells and the expression of its specific marker Muc5ac, among which the best induction effect was observed after 72 h in vitro culture with 5 μmol/L CHIR-99021. Under optimal culture conditions, CHIR-99021 increased the expression levels of the Wnt/β-catenin signaling pathway factors Frzb, β-catenin, SAM pointed domain containing ETS transcription factor, and glycogen synthase kinase-3β and the levels of the Notch signaling pathway factors Notch1 and Krüppel-like factor 4 while decreasing the expression levels of Jagged-1 and Hes1. The expression level of ABCG 2 , a marker of epithelial stem cells, was raised to keep rabbit conjunctival epithelial cells from self-renewing. Our study showed that CHIR-99021 stimulation successfully activated the Wnt/β-catenin signaling pathway and conjunctival goblet cell differentiation was stimulated, in which the Notch signaling pathway played a combined role. Those results provide a novel idea for the expansion of goblet cells in vitro. • CHIR-99021 can increase the stemness of rabbit conjunctival epithelial cells. • CHIR-99021 can promote the differentiation of conjunctival goblet cells and the expression of its specific marker Muc5ac. • CHIR-99021 regulates the differentiation of goblet cells by activating the Wnt/β-catenin pathway in rabbit conjunctival epithelial cells. • Notch pathway may play a cascade role in regulating the differentiation of conjunctival goblet cells under the CHIR-99021 condition. [ABSTRACT FROM AUTHOR]

Objective: To explore the regulatory effect of paeoniflorin on mucin 5AC （MUC5AC） secretion based on NF-κB signaling pathway. Methods: In vivo experiments used a combination of smoke stimulation and chronic infection to replicate the acute exacerbation of COPD rat model, and in vitro experiments used IL-1β to induce human airway epithelial H292 cells to establish an inflammatory hypersecretion model. The experiments included control group, model group, NF- κB pathway inhibitor （PDTC） group, and paeoniflorin group. The pulmonary function of rats in each group was detected by an animal lung function measuring instrument; the expression level of MUC5AC, TNF-α and the inflammatory factor IL-8 in the bronchoalveolar lavage fluid（ BALF）, serum and cell supernatant of each group were detected by ELISA. The expression levels of P65 and inhibitor of nuclear factor κB（ IκB） in each group were detected by Western blot test; the expression of MUC5AC mRNA and cystic fibrosis transmembrane transduction regulator （CFTR） mRNA were detected by reverse transcription real-time fluorescent quantitative polymerase chain reaction（ RT-PCR）. Results: Compared with control group, there were significant differences in respiratory frequency（ f）, peak expiratory flow（ PEF）, tidal volume （VT） and respiratory resistance （Rin） in model group （P<0.05）. Compared with model group, the PEF, VT and Rin of rats in the PDTC group and paeoniflorin group were significantly improved （P<0.05）, and at the same time the f in PDTC group was significantly reduced （P<0.05）. Compared with control group, the contents of MUC5AC, IL-8 and TNF- α in the bronchoalveolar lavage fluid （BALF）, serum and cell supernatant of model group increased significantly （P<0.05）, and the expression of P65 protein and MUC5AC mRNA increased significantly（ P<0.05）. However, the IκB protein decreased significantly（ P<0.05）. Compared with model group, the contents of MUC5AC, IL-8 and TNF-α in BALF, serum and cell supernatant of rats in paeoniflorin group and PDTC group were reduced significantly （P<0.05）, and the expression of IκB protein and CFTR mRNA in PDTC group, high and low dose groups of paeoniflorin increased significantly （P<0.05）, and the expression of P65 protein, MUC5AC mRNA decreased significantly （P<0.05）. Conclusion: Paeoniflorin can improve pulmonary function and reduce airway inflammation of rats in acute exacerbation of COPD, and the mechanism may be related to inhibiting the activity of NF-κB signaling pathway, reducing the secretion of inflammatory factors in airway cells, and regulating the expressions of MUC5AC mRNA, CTFR mRNA and related proteins. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes. Methods Independent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with tumor necrosis factor (TNF) concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality. Results MUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF (P = 1.8 × 10−8) and IFN-γ (P = 2.3 × 10−6). In an additive genetic model, rs28737416 T/T genotype was associated with higher susceptibility to TBM (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.03–1.49; P =.02), but not pulmonary tuberculosis (OR, 1.11, 95% CI,.98–1.25; P =.10). TBM mortality was higher among participants with the rs28737416 T/T and T/C genotypes (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank P =.005) in a Vietnam discovery cohort (n = 210), an independent Vietnam validation cohort (n = 87; 9/87, 19.1% vs 1/20, 2.5%; log-rank P =.02), and an Indonesia validation cohort (n = 468, 127/287, 44.3% vs 65/181, 35.9%; log-rank P =.06). Conclusions MUC5AC variants may contribute to immune changes that influence TBM outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Myopia prevalence among adolescents is increasing annually. While orthokeratology (OK) is effective for controlling myopia progression, it may also be detrimental. We investigated tear film parameters [including tear mucin 5AC (MUC5AC) concentration] in children and adolescents with myopia treated with spectacles or OK compared with those with emmetropia. Methods: This prospective case–control study enrolled children (aged 8–12 years; 29 and 39 with myopia treated with OK and spectacles, respectively, and 25 with emmetropia) and adolescents (aged 13–18 years; 38 and 30 with myopia treated with OK and spectacles, respectively, and 18 with emmetropia). We recorded the ocular surface disease index (OSDI), visual analog scale (VAS) score, tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), meibomian gland score (meiboscore), ocular redness score, and tear MUC5AC concentration in the emmetropia, spectacle (after 12 months of spectacle wearing), and OK (baseline, and after 1-, 3-, 6-, and 12-month use) groups. We observed changes from baseline to 12 months in the OK group and compared parameters among the spectacle, 12-month OK, and emmetropia groups. Results: The 12-month OK group differed significantly from the spectacle and emmetropia groups in most indicators among children and adolescents (P < 0.05). Differences were not noticeable between the spectacle and emmetropia groups (only PVAS < 0.05 among the children). In the OK group, the 12-month NIBUT was significantly decreased (P < 0.05) in both age groups; the upper meiboscore was increased at 6 and 12 months (both P < 0.05) among children; ocular redness scores were higher at 12 months than at baseline (P = 0.007), 1 month (P < 0.001), and 3 months (P = 0.007) among children; and the MUC5AC concentration was decreased at 6 and 12 months among adolescents, but only at 12 months among children (all P < 0.05). Conclusions: Long-term OK can negatively influence the tear film in children and adolescents. Moreover, changes are masked by spectacle wearing. Trial Registration: This trial is registered with "ChiCTR2100049384." [ABSTRACT FROM AUTHOR]

YPL-001 is a drug substance of Pseudolysimachion rotundum var. subintegrum and has been reported to be a potent COPD inhibitor. For the first time, this study demonstrated a correlation among the iridoid constituents, antioxidants, and MUC5AC inhibition activities in P. rotundum during different growth stages (5 to 11 weeks). Single-factor extraction was used to optimize the plant extraction conditions to maximize the major iridoid constituents (70% ethanol, 40 °C, 1 h); isolated metabolites 1–6 were identified using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The contents of each metabolite and antioxidant/MUC5AC inhibition effects were markedly changed according to the growth stages, especially for catalposide (2, 5.97 → 10.99 mg/g, 1.8-fold) and isovanillyl catapol (5, 4.42 → 20.00 mg/g, 4.5-fold), which were the predominant substances in August. Our results indicated that YPL-001 could potentially contribute to enhancing the P. rotundum value in accumulated iridoids at the growth stage and the biological effect aspects to develop industrial medicinal crops. [ABSTRACT FROM AUTHOR]