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Cell Host & Microbe Jul 2023The colon mucus layer is organized with an inner colon mucus layer that is impenetrable to bacteria and an outer mucus layer that is expanded to allow microbiota... (Review)
Review
The colon mucus layer is organized with an inner colon mucus layer that is impenetrable to bacteria and an outer mucus layer that is expanded to allow microbiota colonization. A major component of mucus is MUC2, a glycoprotein that is extensively decorated, especially with O-glycans. In the intestine, goblet cells are specialized in controlling glycosylation and making mucus. Some microbiota members are known to encode multiple proteins that are predicted to bind and/or cleave mucin glycans. The interactions between commensal microbiota and host mucins drive intestinal colonization, while at the same time, the microbiota can utilize the glycans on mucins and affect the colonic mucus properties. This review will examine this interaction between commensal microbes and intestinal mucins and discuss how this interplay affects health and disease.
Topics: Intestinal Mucosa; Mucin-2; Intestines; Mucus; Mucins; Microbiota; Polysaccharides
PubMed: 37442097
DOI: 10.1016/j.chom.2023.05.026 -
Mediators of Inflammation 2023Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and... (Review)
Review
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.
Topics: Humans; Cough; Pulmonary Disease, Chronic Obstructive; Mucus; Lung; Sputum
PubMed: 37457746
DOI: 10.1155/2023/8840594 -
American Journal of Respiratory and... Nov 2023
Randomized Controlled Trial
Topics: Humans; Antibodies, Monoclonal, Humanized; Asthma; Double-Blind Method; Injections, Subcutaneous; Mucus; Severity of Illness Index; Treatment Outcome
PubMed: 37603097
DOI: 10.1164/rccm.202306-1102LE -
Gut Jul 2023infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show...
OBJECTIVE
infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between infection and colon cancer is lacking.
DESIGN
We infected two -mutant mouse models and C57BL/6 mice with and conducted a comprehensive analysis of -induced changes in intestinal immune responses and epithelial signatures via flow cytometry, chip cytometry, immunohistochemistry and single cell RNA sequencing. Microbial signatures were characterised and evaluated in germ-free mice and via stool transfer experiments.
RESULTS
infection accelerated tumour development in -mutant mice. We identified a unique -driven immune alteration signature characterised by a reduction in regulatory T cells and pro-inflammatory T cells. Furthermore, in the intestinal and colonic epithelium, induced pro-carcinogenic STAT3 signalling and a loss of goblet cells, changes that have been shown to contribute-in combination with pro-inflammatory and mucus degrading microbial signatures-to tumour development. Similar immune and epithelial alterations were found in human colon biopsies from -infected patients. Housing of -mutant mice under germ-free conditions ameliorated, and early antibiotic eradication of infection normalised the tumour incidence to the level of uninfected controls.
CONCLUSIONS
Our studies provide evidence that infection is a strong causal promoter of colorectal carcinogenesis. Therefore, implementation of status into preventive measures of CRC should be considered.
Topics: Humans; Mice; Animals; Helicobacter pylori; Helicobacter Infections; Mice, Inbred C57BL; Carcinogenesis; Stomach Neoplasms; Colonic Neoplasms; Microbiota; Mucus; Gastric Mucosa
PubMed: 37015754
DOI: 10.1136/gutjnl-2022-328075 -
Biomaterials Aug 2023Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and...
Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and highly non-responsive. Recently, we discovered that a natural adhesive from snail mucus can promote skin wound healing. Herein, inspired by the finding, we developed a double-network hydrogel biomaterial that composed of snail glycosaminoglycan (AFG) and methacrylated gelatin (GelMA), in which AFG is the main bioactive component of snail mucus and GelMA provides a scaffold mimicking the proteins in snail mucus. The biomimetic hydrogel exhibited strong tissue adhesion, potent anti-inflammatory activity, and excellent biocompatibility. The biodegradable AFG/GelMA hydrogel markedly promoted chronic wound healing in both STZ-induced type 1 diabetic rat and db/db mouse models after a single treatment. Further mechanistic research showed that the hydrogel significantly attenuated inflammation by sequestrating pro-inflammatory cytokines, as well as downregulated their expression by inhibiting NF-ĸB signaling pathway, and it can also promote macrophage polarization to M2 phenotype. Taken together, the bioinspired hydrogel can effectively promote the transition of chronic wounds from inflammation to proliferation stage. These data suggest that the AFG/GelMA hydrogel is a promising therapeutic biomaterial for the treatment of chronic diabetic wounds.
Topics: Mice; Rats; Animals; Hydrogels; Gelatin; Wound Healing; Biocompatible Materials; Diabetes Mellitus; Cytokines; Macrophages
PubMed: 37167893
DOI: 10.1016/j.biomaterials.2023.122141 -
Allergology International : Official... Jul 2024Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed... (Review)
Review
Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.
Topics: Humans; Eosinophilia; Mucus; Eosinophils; Animals; Sinusitis
PubMed: 38594175
DOI: 10.1016/j.alit.2024.03.002 -
Chest Jul 2023We previously showed in patients with poorly controlled eosinophilic asthma that a single dose of benralizumab resulted in significantly improved Asthma Control...
BACKGROUND
We previously showed in patients with poorly controlled eosinophilic asthma that a single dose of benralizumab resulted in significantly improved Asthma Control Questionnaire (ACQ-6) score and Xe MRI ventilation defect percent (VDP) 28 days postinjection, and Xe MRI VDP and CT airway mucus occlusions were shown to independently predict this early ACQ-6 response to benralizumab.
RESEARCH QUESTION
Do early VDP responses at 28 days persist, and do FEV, fractional exhaled nitric oxide, and mucus plug score improve during a 2.5 year treatment period?
STUDY DESIGN AND METHODS
Participants with poorly controlled eosinophilic asthma completed spirometry, ACQ-6, and MRI, 28 days, 1 year, and 2.5 years after initiation of treatment with benralizumab; chest CT was acquired at enrollment and 2.5 years later.
RESULTS
Of 29 participants evaluated at 28 days post-benralizumab, 16 participants returned for follow-up while on therapy at 1 year, and 13 participants were evaluable while on therapy at 2.5 years post-benralizumab initiation. As compared with 28 days post-benralizumab, ACQ-6 score (2.0 ± 1.4) significantly improved after 1 year (0.5 ± 0.6, P = .02; 95% CI, 0.1-1.1) and 2.5 years (0.5 ± 0.5, P = .03; 95% CI, 0.1-1.1). The mean VDP change at 2.5 years (-4% ± 3%) was greater than the minimal clinically important difference, but not significantly different from VDP measured 28 days post-benralizumab. Mucus score (3 ± 4) was significantly improved at 2.5 years (1 ± 1, P = .03; 95% CI, 0.3-5.5). In six of eight participants with previous occlusions, mucus plugs vanished or substantially diminished 2.5 years later. VDP (P < .001) and mucus score (P < .001) measured at baseline, but not fractional exhaled nitric oxide or FEV, independently predicted ACQ-6 score after 2.5 years.
INTERPRETATION
In poorly controlled eosinophilic asthma, early MRI VDP responses at 28 days post-benralizumab persisted 2.5 years later, alongside significantly improved mucus scores and asthma control.
Topics: Humans; Nitric Oxide; Asthma; Pulmonary Eosinophilia; Airway Obstruction; Mucus; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Anti-Asthmatic Agents
PubMed: 36781102
DOI: 10.1016/j.chest.2023.02.009 -
American Journal of Respiratory and... Feb 2024Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular...
Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia. Morphologic criteria and region-specific epithelial gene expression, measured histologically and by RNA hybridization and immunohistochemistry, identified proximal and distal bronchioles in excised NCFB lungs. RNA hybridization and immunohistochemistry assessed bronchiolar mucus accumulation and mucin gene expression. CRISPR-Cas9-mediated IL-1R1 knockout in human bronchial epithelial cultures tested IL-1α and IL-1β contributions to mucin production. Spatial transcriptional profiling characterized NCFB distal bronchiolar gene expression. Bronchiolar perimeters and lumen areas per section area were increased in proximal, but not distal, bronchioles in NCFB versus control lungs, suggesting proximal bronchiolectasis. In NCFB, mucus plugging was observed in ectatic proximal bronchioles and associated nonectatic distal bronchioles in sections with disease. MUC5AC and MUC5B mucins were upregulated in NCFB proximal bronchioles, whereas MUC5B was selectively upregulated in distal bronchioles. Bronchiolar mucus plugs were populated by IL-1β-expressing macrophages. NCFB sterile sputum supernatants induced human bronchial epithelial MUC5B and MUC5AC expression that was >80% blocked by IL-1R1 ablation. Spatial transcriptional profiling identified upregulation of genes associated with secretory cells, hypoxia, interleukin pathways, and IL-1β-producing macrophages in mucus plugs and downregulation of epithelial ciliogenesis genes. NCFB exhibits distinctive proximal and distal bronchiolar disease. Both bronchiolar regions exhibit bronchiolar secretory cell features and mucus plugging but differ in mucin gene regulation and ectasia.
Topics: Humans; Bronchioles; Dilatation, Pathologic; Bronchiectasis; Cystic Fibrosis; Mucins; Interleukin-1beta; Fibrosis; RNA; Mucin 5AC
PubMed: 38016030
DOI: 10.1164/rccm.202306-1093OC